bluuebunny/crossref_metadata_2025 huggingface dataset:
Automated collection of double red blood cell units with a variable‐volume separation chamber
Authors: AuBuchon James P. , Dumont Larry J. , Herschel Louise , Roger Jill , Beddard Rachel L. , Taylor Harry L. , Whitley Pamela H. , Sawyer Sherrie L. , Graminske Sharon , Martinson Karen , Dora Ross , Heldke Sybil , Adamson John , Rose Leslie E.
Published: September 2007

BACKGROUND: Automated collection of blood components offers multiple advantages and has prompted development of portable devices. This study sought to document the biochemical and hematologic properties and in vivo recovery of red cells (RBCs) collected via a new device that employed a variable‐volume centrifugal separation chamber.

STUDY DESIGN AND METHODS: Normal subjects (n = 153) donated 2 units of RBCs via an automated blood collection system (Cymbal, Haemonetics). Procedures were conducted with wall outlet power (n = 49) or the device's battery source (n = 104). Units were collected with or without leukoreduction filtration and were stored in AS‐3 for 42 days. The units were assessed via standard biochemical and hematologic tests before and after storage, and 24 leukoreduced (LR) and 24 non‐LR RBCs were radiolabeled on Day 42 with Na251CrO4 for autologous return to determine recovery at 24 hours with concomitant determination of RBC volume via infusion of 99mTc‐labeled fresh RBCs.

RESULTS: Two standard RBC units (targeted to contain 180 mL of RBCs plus 100 mL of AS‐3) could be collected in 35.7 ± 2.0 minutes (n = 30) or 40.3 ± 2.7 minutes for LR RBCs (n = 92). An additional 31 collections were conducted successfully with intentional filter bypassing. RBC units contained 104 ± 4.1 percent of their targeted volumes (170‐204 mL of RBCs), and LR RBCs contained 92 percent of non‐LR RBCs' hemoglobin. All LR RBCs contained less than 1 × 106 white blood cells. Mean hemolysis was below 0.8 percent (Day 42) for all configurations. Adenosine triphosphate was well preserved. Mean recovery was 82 ± 4.9 percent for RBCs and 84 ± 7.0 percent for LR RBCs.

CONCLUSIONS: The Cymbal device provided quick and efficient collection of 2 RBC units with properties meeting regulatory requirements and consistent with good clinical utility.
A probabilistic model for analyzing viral risks of plasma‐derived medicinal products
Authors: Janssen Mart P. , Over Jan , Van Der Poel Cees L. , Cuijpers H. Theo M. , Van Hout Ben A.
Published: September 2007

BACKGROUND: The prevention of transmission of viral infections by plasma‐derived medicinal products is of concern to manufacturers, legislators, and patient representative groups. Recent European legislation requires a viral risk assessment for all new marketing applications of such products.

STUDY DESIGN AND METHODS: A discrete event Monte Carlo model was developed to determine the viral transmission risks of the plasma‐derived medicinal products. The model incorporates donor epidemiology, donation intervals, efficiency of screening tests for viral markers, inventory hold period, size and composition of the manufacturing pool, production time, process virus reduction capacity, and product yield. With the model, the human immunodeficiency virus (HIV) and hepatitis C virus (HCV) contamination risks of a typical hypothetical plasma product were calculated, and the sensitivity of the risk to various model variables was analyzed.

RESULTS: The residual HIV and HCV risks of the finished products are linear in change with viral incidence rate and inversely linear with product yield and process virus reduction capacity. For the product analyzed in this article, the residual risk is less sensitive to changes in screening test pool size, donation frequency, and inventory hold period. There is only a limited dependency on the donation type (apheresis or whole‐blood donations) and a negligible dependency on the manufacturing pool size.

CONCLUSIONS: The use of probabilistic model simulation techniques is indispensable when estimating realistic residual viral risks of plasma‐derived medicinal products. In contrast to conventional deterministic residual risk estimations, the probabilistic approach allows incorporation of specific manufacturing decisions and therefore provides the only feasible alternative for a correct assessment of residual risks.
Automated Left Ventricular Capture Management
Authors: CROSSLEY GEORGE H. , MEAD HARDWIN , KLECKNER KAREN , SHELDON TODD , DAVENPORT LYNN , HARSCH MANYA R. , PARIKH PURVEE , RAMZA BRIAN , FISHEL ROBERT , BAILEY J. RUSSELL ,   for the LVCM Study Investigators
Published: September 2007

Background:

The stimulation thresholds of left ventricular (LV) leads tend to be less reliable than conventional leads. Cardiac resynchronization therapy (CRT) requires continuous capture of both ventricles.

Objective:

The purpose of this study is to evaluate a novel algorithm for the automatic measurement of the stimulation threshold of LV leads in cardiac resynchronization systems.

Methods:

We enrolled 134 patients from 18 centers who had existing CRT‐D systems. Software capable of automatically executing LV threshold measurements was downloaded into the random access memory (RAM) of the device. The threshold was measured by pacing in the left ventricle and analyzing the interventricular conduction sensed in the right ventricle. Automatic LV threshold measurements were collected and compared with manual LV threshold tests at each follow‐up visit and using a Holter monitor system that recorded both the surface electrocardiograph (ECG) and continuous telemetry from the device.

Results:

The proportion of Left Ventricular Capture Management (LVCM) in‐office threshold tests within one programming step of the manual threshold test was 99.7% (306/307) with a two‐sided 95% confidence interval of (98.2%, 100.0%). The algorithm measured the threshold successfully in 96% and 97% of patients after 1 and 3 months respectively. Holter monitor analysis in a subset of patients revealed accurate performance of the algorithm.

Conclusion:

This study demonstrated that the LVCM algorithm is safe, accurate, and highly reliable. LVCM worked with different types of leads and different lead locations. LVCM was demonstrated to be clinically equivalent to the manual LV threshold test. LVCM offers automatic measurement, output adaptation, and trends of the LV threshold and should result in improved ability to maintain LV capture without sacrificing device longevity.
Effect of Posterolateral Left Ventricular Scar on Mortality and Morbidity following Cardiac Resynchronization Therapy
Authors: CHALIL S. , STEGEMANN B. , MUHYALDEEN S. A. , KHADJOOI K. , FOLEY P. W. , SMITH R.E.A. , LEYVA F.
Published: September 2007

Objectives:

To determine the effect of a posterolateral (PL) left ventricular scar on mortality and morbidity following cardiac resynchronization therapy (CRT).

Methods:

Sixty‐two patients with heart failure (age 67.3 ± 9.6 yrs [mean ± SD], 45 males, New York Heart Association class [NYHA] class III or IV, left ventricular ejection fraction [LVEF]= 35%, left bundle branch block, QRS  ≥ 120 ms) underwent late gadolinium enhancement cardiovascular magnetic resonance (LGE‐CMR) for scar imaging. Patients were followed up for 741 (75–1602) days (mean [range]).

Results:

The presence of a PL scar emerged as an independent predictor of the composite endpoint of cardiovascular death or hospitalization for worsening heart failure (HR: 3.06 [1.63, 7.7, P < 0.0001]) as well as the endpoint of cardiovascular death (HR: 2.63 [1.39, 6.65], P = 0.0016). A transmural PL scar was the strongest predictor of these endpoints (both P < 0.0001). The symptomatic responder rate (improvement by ≥1 NYHA classes or ≥25% in 6‐min walking distance) was 83% in the group with non‐PL scars, but only 47% in the group with transmural PL scars (P < 0.0001). Pacing over the scar was associated with a higher mortality and morbidity than pacing outside the scar (all P < 0.05).

Conclusions:

A PL scar is associated with a worse clinical outcome following CRT, particularly if it is transmural. Pacing scarred left ventricular myocardium carries a greater risk of mortality and morbidity than pacing nonscarred myocardium.
Site Localization and Characterization of Pain During Radiofrequency Ablation of the Pulmonary Veins
Authors: ALAEDDINI JAMSHID , WOOD MARK A. , PARVEZ BABER , PATHAK VISHESH , WONG KRISTEN A. , ELLENBOGEN KENNETH A.
Published: September 2007

Background:

Characteristics of radiofrequency (RF) lesions producing pain with an 8‐mm catheter during pulmonary vein (PV) ablation have not been prospectively studied.

Methods:

We studied 46 (30 men, age 56 ± 10 years) patients with AF who underwent RF ablation of PVs. PV isolation was achieved by using an 8F, 8‐mm Biosense™ ablation catheter (Biosense Webster, Diamond Bar, CA, USA) guided by intracardiac echocardiography (ICE). An electroanatomic map was used to document the location of all RF lesions and the time; PV location and maximum temperature of every lesion were recorded. Location of the esophagus was determined by magnetic resonance imaging prior to the procedure and by both ICE and barium swallows during procedure.

Result:

A total of 1,448 (33 ± 12) RF lesions were delivered to 180 veins. Thirty‐nine patients (85%) had at least one lesion associated with pain (mean: 8 ± 5 lesions) during ablation. The RF generator setting during lesions resulting in pain sensation was 48.6 ± 7.0 Watts and 51.5 ± 2.9°C. Maximum temperature attained at the time of pain sensation was 45.7 ± 4.2°C. By logistic regression analysis the left superior PV (OR 1.54, CI 1.06–2.24, LS vs RI, P < 0.05) and left inferior PV (OR 2.74, CI 1.79–4.19, LI vs RI, P < 0.001) location were both positively correlated with the production of pain. The location of lesions associated with pain was not near the esophagus during any of the pain‐producing lesions.

Conclusion:

Pain sensation is relatively common during RF ablation of PVs. There was no correlation between pain and the location of esophagus. Pain was more common during RF ablation of left inferior and left superior PVs.
Swallowing‐Induced Atrial Tachyarrhythmias: Prevalence, Characteristics, and the Results of the Radiofrequency Catheter Ablation
Authors: TADA HIROSHI , KASENO KENICHI , KUBOTA SHOICHI , NAITO SHIGETO , YOKOKAWA MIKI , HIRAMATSU SHIGEKI , GOTO KOJI , NOGAMI AKIHIKO , OSHIMA SHIGERU , TANIGUCHI KOICHI
Published: September 2007

Background:

Detailed information on swallowing‐induced tachyarrhythmias has been lacking.

Methods:

The prevalence, characteristics, and results of the radiofrequency catheter ablation (RFCA) of swallowing‐induced tachyarrhythmias were examined in 544 patients with symptomatic premature atrial contractions (PACs), paroxysmal atrial tachycardia (AT), and/or paroxysmal atrial fibrillation (AF). We also conducted a search of the medical literature on swallowing‐induced tachyarrhythmias. Further, we presented an in‐depth review of the literature and investigated the published data on swallowing‐induced tachyarrhythmias.

Results:

The prevalence of swallowing‐induced tachyarrhythmias was 0.6% (three patients). An analysis of the published literature and our three cases demonstrated that (1) males predominated 9:1 over females, (2) most cases occurred over 35 years of age, (3) tachyarrhythmias occurred consistently and reproducibly shortly after each swallow, (4) 90% of the patients had PACs and/or AT as the manifesting arrhythmia, (5) the PACs provoked by swallowing usually had the same P‐wave morphology as the first beat of the AT and AF, and (6) RFCA procedures performed in five cases resulted in success with no recurrence or complications.

Conclusions:

Swallowing‐induced tachyarrhythmias are rare, but have several distinct characteristics. RFCA should be considered in appropriately selected patients with reliable inducibility because such an ablation may offer a permanent cure.
Effect of Nifekalant for Acute Conversion of Atrial Flutter: The Possible Termination Mechanism of Typical Atrial Flutter
Authors: MORITA NORISHIGE , TANAKA KEIJI , YODOGAWA KENJI , HAYASHI MEISO , AKUTSU KOICHI , YAMAMOTO TAKESHI , SATOH NAOKI , KOBAYASHI YOSHINORI , KATOH TAKAO , TAKANO TERUO
Published: September 2007

Background:

Nifekalant is a class III antiarrhythmic drug, which is usually used for suppression of ventricular tachycardia (VT) and fibrillation. We studied the efficacy of nifekalant for acute conversion of atrial flutter (AFL) in a prospective, open label study in the intensive care unit (ICU) of cardiovascular medicine.

Methods:

This study consisted of 31 patients. Twenty‐six patients (84%) suffered from structural heart diseases. AFL was developed in 15 patients (48%) while on antiarrhythmic therapy with class IA or IC drugs (I‐AFL group) for suppressing atrial fibrillation (AF) and in the remaining patients without such drugs (S‐AFL group). Patients with prolonged QT interval, hypokalemia were excluded. All patients received one dose of 0.3 mg/kg of nifekalant over 10 minutes under continuous ambulatory monitoring. Four patients with common AFL in each group received nifekalant during electrophysiologic (EP) study.

Results:

Nifekalant had an overall AFL conversion efficacy of 77.4% within 60 minutes. Eleven patients in S‐AFL group (68.8%) and 13 patients in I‐AFL group (86.7%) could be converted with mean conversion times of 10.8 ± 6.2 and 15.0 ± 8.0 minutes, respectively (n.s.). Conversion rate was significantly higher in patients with a short duration of arrhythmia. The two modes of AFL termination were mainly demonstrated and the preferential mode significantly differed between the two groups. One patient in each group with excessive QT prolongation (6.5%) developed torsade de pointes (TdP), requiring electrical shock in one patient (3.3%).

Conclusions:

Nifekalant can be used for conversion of AFL with a potent efficacy even in patients with structural heart diseases. However, caution should be required for developing TdP.
Predictors of Cardiac Arrest Occurring in the Context of Acute Myocardial Infarction
Authors: HREYBE HAITHAM , SINGLA ISH , RAZAK EATHAR , SABA SAMIR
Published: September 2007

Background:Cardiac arrest (CA) concurrent with acute myocardial infarction (AMI) claims the life of many patients with coronary artery disease (CAD). In this study, we investigated the predictors of CA during AMI.

Method:Patients admitted with CA concurrent with AMI (n = 31) were matched by age, gender, race, and left ventricular ejection fraction (LVEF) to patients with AMI but no CA (n = 70). All patients underwent coronary angiography. Binary logistic regression was used to identify independent predictors of CA during AMI.

Results:A total of 101 patients (age = 61 ± 13 years, men 76%, Caucasians 98%, LVEF 33 ± 12%) admitted to the University of Pittsburgh Medical Center with AMI were included in this analysis. Patients with CA concurrent with the AMI were more likely to have proximal rather than distal coronary artery culprit lesions (odds ratio (OR) = 7.2, P = 0.019). Other predictors of CA in the context of AMI included negative family history of CAD (OR = 8.0, P = 0.026) and absence of sinus rhythm upon hospital admission (OR = 5.1, P = 0.030).

Conclusion:Proximity of culprit coronary lesion and presence of rhythm other than sinus rhythm at hospital admission are two strong predictors of CA in the context of AMI. The implication is that the mechanism of CA is primarily that of a large area of myocardial ischemia leading to lethal ventricular arrhythmia. Other predispositions such as genetic make‐up cannot be ruled out.
Relationship Between Abnormal Microvolt T‐Wave Alternans and Poor Glycemic Control in Type 2 Diabetic Patients
Authors: MOLON GIULIO , COSTA ALESSANDRO , BERTOLINI LORENZO , ZENARI LUCIANO , ARCARO GUIDO , BARBIERI ENRICO , TARGHER GIOVANNI
Published: September 2007

Background:

Abnormal microvolt T‐wave alternans (TWA) predicts the risk of ventricular arrhythmias and sudden cardiac death. Although type 2 diabetes is associated with an increased risk of these events, there is a dearth of available data on microvolt TWA measurements in type 2 diabetic populations.

Methods:

We studied 59 consecutive type 2 diabetic outpatients without manifest cardiovascular disease (CVD) and 35 non‐diabetic controls who were matched for age, sex, and blood pressure values. Microvolt TWA analysis was performed non‐invasively using the CH‐2000 system during a sub‐maximal exercise with the patient sitting on a bicycle ergometer.

Results:

The frequency of abnormal TWA was significantly higher in diabetic patients than in controls (25.4 vs 5.7%; P < 0.01). Among diabetic patients, those with abnormal TWA (n = 15) had remarkably higher hemoglobin A1c (HbA1c) (8.1 ± 0.9 vs 7.1 ± 0.8%, P < 0.001) and slightly smaller time‐domain heart rate variability parameters (i.e., RMSSD, root mean square of difference of successive R‐R intervals) than those with normal TWA (n = 44). Gender, age, body mass index, lipids, blood pressure values, cigarette smoking, diabetes duration, microvascular complication status, QTc interval, and current use of medications did not significantly differ between the groups. In multivariate regression logistic analysis, HbA1c (OR 13.6, 95% CI 2.0–89.1; P = 0.0076) predicted abnormal TWA independent of RMSSD values and other potential confounders.

Conclusions:

Our findings suggest that abnormal TWA is a very common condition (∼25%) among people with type 2 diabetes without manifest CVD and is closely correlated to glycemic control.
Pacemaker Endocarditis in Patients with Prosthetic Valve Replacements: Case Trilogy and Literature Review
Authors: JENKINS SHONA M. M. , HAWKINS NATHANIEL M. , HOGG KERRY J.
Published: September 2007

Infective endocarditis is not uncommon in patients with both a permanent pacemaker system and a prosthetic valve. No guidelines exist to aid management. The recommendations for pacemaker infective endocarditis alone are limited and contradictory. We present a case trilogy and literature review that highlights these shortcomings and the challenges facing physicians. Complete extraction of the infected pacemaker system is essential. The timing of extraction, duration of antibiotic therapy, and timing of reimplantation are all controversial. The presence of a concomitant prosthetic valve exacerbates these dilemmas further.
Removal of Coronary Sinus Intima by a Guidewire during Cardiac Resynchronization Therapy
Authors: ADACHI MASAMITSU , IGAWA OSAMU , INOUE YOSHIAKI , HISATOME ICHIRO
Published: September 2007

Previously, complications associated with the placement of the left ventricular pacing lead were reported in 1.9–6% of cases. We describe a case with a stripping of venous intima from the coronary sinus by a guidewire during a left ventricular lead implantation. Judging from this case, the firm guidewire and coronary catheter should not be used within the coronary sinus.
Opening an Occluded Subclavian Vein with a Screw‐Like Flexible Hollow Guide‐wire and Venoplasty
Authors: JOSEPH WORLEY SETH , CHARLES GOHN DOUGLAS , WARD PULLIAM ROBERT
Published: September 2007

Patients with existing internal cardioverter defibrillators (ICDs) often require upgrading to a biventricular ICD for treatment of congestive heart failure (CHF). Placement of a left ventricular (LV) lead can be technically challenging in the best of circumstances. A subclavian vein stenosis or occlusion related to previously placed leads adds a major obstacle to a successful implant. We report a technique of implanting an LV lead from the same side as the existing ICD system despite complete occlusion of the subclavian vein.
Low Exposure Radiation with Conventional Guided Radiofrequency Catheter Ablation in Pregnant Women
Authors: BERRUEZO ANTONIO , DÍEZ GERARDO RODRÍGUEZ , BERNE PAOLA , ESTEBAN MARIANA , MONT LLUIS , BRUGADA JOSEP
Published: September 2007

Cardiac arrhythmias in pregnant women are a common entity and often drug‐refractory. The major concern about using radiofrequency (RF) catheter ablation guided by fluoroscopy to treat arrhythmias during pregnancy is the potential consequences of exposing the fetus to radiation. We present two pregnant patients with incessant and life‐threatening supraventricular tachycardias successfully treated by conventional RF ablation under strict radioactive dosimeter surveillance. The availability of better fluoroscopy and lead shielding techniques allows to perform RF ablation of drug‐refractory and poorly tolerated supraventricular arrhythmias at any stage of pregnancy, with an appropriate tracking of the radiation dose received by both mother and fetus.
Age‐Dependency of Classic and New Parameters of Diastolic Function
Authors: Wierzbowska‐Drabik Karina , Krzemińska‐Pakuła Maria , Chrzanowski Łukasz , Plewka Michał , Waszyrowski Tomasz , Drożdż Jarosław , Kurpesa Małgorzata , Trzos Ewa , Kasprzak Jarosław D.
Published: September 2007

Age‐dependency has been demonstrated for classic diastolic parameters but is less documented for novel markers. We compared wide spectrum of diastolic measurements in healthy subjects younger and older than 50 and 70 years. Method: In 80 subjects (17 to 91 year, 38 male, mean age 53 ± 16) we assessed in transthoracic echocardiography mitral inflow, pulmonary vein flow, propagation velocity, and tissue Doppler parameters. The data were compared between the groups: A < 50, B 50–70, and C > 70 years and their correlation with age was analyzed. Result: In the older groups a longer duration of isovolumic relaxation, higher velocity of mitral inflow atrial phase, and lower early to atrial mitral inflow velocity ratio (E/A) were observed. In pulmonary veins ratio of peak systolic to diastolic velocity (S/D) was higher and atrial reversal flow faster. Among the new parameters in older groups a lower propagation velocity of early wave (Ep) (30 ± 8 in C, 44 ± 10 in B vs 49±9 cm/s in A;
P
< 0.05) and peak early diastolic velocity of mitral annulus (E' 9.5 ± 1.8 in C and 11.2 ± 2.9 in B vs 15.8 ± 4.1 cm/s in A,
P
< 0.05) were recorded. Conclusions: Besides the evolution of mitral inflow toward the delayed relaxation profile in elderly, a decrease of propagation and tissue Doppler velocities were documented. The strongest positive correlation with age was observed for atrial velocity of mitral inflow (A, r = 0.63) and inverse correlation for E/A ratio (r =–0.6) and early diastolic velocity of mitral annulus (r =–0.69).
Live/Real Time Three‐Dimensional Transthoracic Echocardiographic Findings in Primary Left Atrial Leiomyosarcoma
Authors: Suwanjutah Thouantosaporn , Singh Harpreet , Plaisance Benjamin R. , Hameed Omar , Nanda Navin C.
Published: September 2007

We describe an adult patient with a primary left atrial leiomyosarcoma in whom live/real time three‐dimensional transthoracic echocardiography showed echolucent areas within the mass consistent with necrosis or hemorrhage surrounded by dense band‐like echo densities indicative of fibrosis or collagen giving a “doughnut” like appearance. These findings were consistent with histopathology, which showed areas of necrosis and dilated vascular channels within the fibrotic tumor. Our case further illustrates the usefulness of three‐dimensional transthoracic echocardiography in characterizing the morphologic features of an intracardiac mass.
Hemodialysis in the United Kingdom
Authors: MACGREGOR Mark S. , CARR Sue J.
Published: September 2007

Hemodialysis was a neglected aspect of nephrology in the UK. At the request of the Renal Association, the first UK Haemodialysis Masterclass was organized in 2007. The articles in this supplement arose from that meeting. Here, an overview of UK hemodialysis services and nephrology training is presented as background. Government‐funded dialysis should be provided to all UK citizens who require it. In 2005, there were 17,645 patients receiving hemodialysis, 5057 on peritoneal dialysis and 19,074 with kidney transplants, looked after by 359 nephrologists working in 73 National Health Service renal units. Renal replacement therapy incidence and prevalence remain comparatively low, at 108 and 694 per million population, respectively. Whether this represents inadequate provision or genuinely lower need remains unclear. The Renal Association sets clinical practice guidelines for dialysis, and audits performance via the UK Renal Registry. Postgraduate medical education is undergoing radical change in the UK. This is driven by the reduction in trainee doctors' working hours to 48 hr/week (mandated by the European Working Time Directive), and the governments' wish to reduce the duration of training, but also by a desire to formalize training, Our challenge is to continue to produce talented clinical nephrologists educated in breadth and depth, despite the reduced emphasis on clinical experience and omission of period of scientific research. The future for hemodialysis services in the UK is, however, promising with an expansion in the number of specialists and dialysis centers, and a growing interest in dialysis practice and research.
Alternatives to standard hemodialysis
Authors: MACGREGOR Mark S.
Published: September 2007

Survival of patients on hemodialysis remains poor, but the benefits of increasing urea clearance have probably been maximized within our current treatment schedules. Long dialysis sessions (8 hr) produce impressive outcomes, with mortality 53% to 55% lower than conventional schedules. Even increasing from 4 to 5 hr may improve survival. Increased frequency of dialysis (6 times weekly) produces impressive reductions in left ventricular mass and could conceivably be implemented in‐center. Preliminary data suggest a 61% reduction in mortality with increased frequency. Nightly dialysis combines longer sessions with increased frequency and has produced remarkable clinical gains in blood pressure, left ventricular mass, serum phosphate, and sleep apnea. However, the data are mainly from case series and impact on mortality remains unknown. Expansion of home hemodialysis would be necessary for this modality to grow. Convective therapies remove middle molecules more effectively, and observational data suggest hemodiafiltration has the potential to improve mortality by 35% to 36%. Hemodiafiltration has the advantage of being relatively easy to implement. The uremic milieu is complex and further investigation of the underlying pathophysiology is needed to inform future dialysis interventions. The survival data above are from observational studies, and hence benefits are likely to be exaggerated. Randomized trials of dialysis interventions are desperately needed. They remain difficult to perform, because of the complexity of both the patient population and the interventions, and because of limited available funding.
Dialysis desiderata*
Authors: WINCHESTER James F. , AMERLING Richard , DUBROW Alan , FEINFELD Donald A. , GRUBER Stephen J. , HARBORD Nikolas , KUNTSEVICH Viktoriya
Published: September 2007

Microarray immunoassay systems, proteomics, separation of polypeptides in plasma by electrophoresis, and detection by mass spectrometry have shown that low molecular weight proteins, cytokines, and chemokines are present in high concentration in chronic kidney disease (CKD) subjects receiving dialysis. That these substances are also found in high concentration in sepsis, postcardiac bypass, acute respiratory distress, burns, and in brain death suggest that these syndromes have a common pathogenesis via a systemic inflammatory response syndrome (SIRS). It is not yet clear whether the profiles of such substances differ among the SIRS states. Dialysis membranes are not capable of removing these substances because such moieties exceed the molecular weight cutoff of modern synthetic hemodialysis membranes. On the other hand, sorbents directly in contact with blood or indirectly with filtered plasma, may be designed with pore structures with the capability of removing these substances. Such sorbents could be exploited in the treatment of CKD. While few human studies have been performed, animal experiments suggest that human trials should be initiated. The potential advantages of sorbents for CKD will be described.
The pivotal role of sodium balance in control of blood pressure in dialysis patients
Authors: TOMSON Charles R. V. , SHRESTHA Sarju M.
Published: September 2007

In hemodialysis patients, as in patients with normal kidney function, sodium balance is the major determinant of changes in extracellular volume, and extracellular volume is an important determinant of blood pressure. The osmotic thresholds for thirst and ADH release are normal in kidney failure; pre‐dialysis serum sodium concentration shows a high index of individuality in oliguric hemodialysis patients. Non‐osmotic storage of sodium in vascular walls may also amplify the volume‐sensitivity of blood pressure. The variable relationship between volume removal and change in blood pressure described in clinical studies reflects a state of permanent volume expansion in those whose blood pressure does not fall, or rises, during dialysis, whereas those whose blood pressure falls during dialysis are those who approach normovolemia. Rigorous control of extracellular volume often results in perfect blood pressure control, but may be difficult to achieve safely other than with long, slow dialysis combined with dietary salt restriction.
Intelligent hemodialysis: Toys or tools?
Authors: LAMBIE Stewart , WARWICK Graham
Published: September 2007

Hemodialysis technology has advanced significantly in recent years, with a variety of new techniques for optimizing treatment now available. It remains to be seen which of these techniques prove to be of significant benefit and which are useful only within the confines of research projects. Some of the recent developments in technology are examined here.
Renal replacement therapy in the critically ill patient with acute kidney injury
Authors: LEWINGTON Andrew J. P.
Published: September 2007

The mortality of patients with acute renal failure (ARF) has remained unacceptably high for many years, with renal replacement therapy (RRT) remaining the mainstay of treatment. Clinical research has hitherto been hindered by a lack of a universal definition. However, changes are upon us in the shape of a new term, acute kidney injury (AKI), proposed to encompass the spectrum of ARF, along with a new definition and staging system. There is a renewed optimism that the establishment of clinical databases and the utilization of new clinical biomarkers will catalyze the development of new therapeutic strategies. In the interim, we must optimize the delivery of RRT to patients with AKI. It is remarkable how few studies are currently available in the literature to guide medical practitioners on the key issues of initiation, modality, type of buffer, dose of RRT, vascular access, and anticoagulation. On the horizon, the outcomes of two major clinical trials comparing doses and modalities of RRT in AKI are eagerly awaited.
Which issues should trials address in hemodialysis?
Authors: WHEELER David C.
Published: September 2007

The number of published randomized controlled trials in nephrology is fewer than in most other specialties in internal medicine. As a consequence, current clinical practice guidelines are based largely on expert opinion, which may prove to be incorrect. Enthusiasm for trials involving hemodialysis patients has been dampened by a series of high profile studies in which a range of different interventions have failed to improve outcomes. Despite these disappointments, recent experience suggests that nephrologists remain willing to participate in clinical studies that address important questions. Previous, ongoing and future trials involving hemodialysis patients are discussed.
Spontaneous retroperitoneal hemorrhage due to acquired cystic kidney disease
Authors: MOORE Ann E. , KUJUBU Dean A.
Published: September 2007

A patient with end‐stage renal disease on maintenance hemodialysis developed sudden severe abdominal pain and distension. He suffered a decline in his hematocrit and subsequent abdominal imaging revealed a large left‐sided retroperitoneal hemorrhage in the setting of atrophic, severely cystic kidneys. He underwent selective left renal artery angiography and embolization due to continued hemorrhage with stabilization in his condition. However, he became paraparetic within hours of the embolization procedure due to spinal cord infarct. Acquired cystic kidney disease is a very common entity in patients with chronic kidney disease. Complications include cystic hemorrhage or infection, erythrocytosis, and renal cell carcinoma. Screening of patients for cystic disease and malignant transformation remains a controversial topic; however, most advocate abdominal imaging after 3 to 5 years on dialysis.
Isolation of human foetal myoblasts and its application for microencapsulation
Authors: Li Anna Aihua , Bourgeois Jacqueline , Potter Murray , Chang Patricia L.
Published: September 2007

Foetal cells secrete more growth factors, generate less immune response, grow and proliferate better than adult cells. These characteristics make them desirable for recombinant modification and use in microencapsulated cellular gene therapeutics. We have established a system in vitro to obtain a pure population of primary human foetal myoblasts under several rounds of selection with non‐collagen coated plates and identified by desmin staining. These primary myoblasts presented good proliferation ability and better differentiation characteristics in monolayer and after microencapsulation compared to murine myoblast C2C12 cells based on creatine phosphokinase (CPK), major histocompatibility complex (MHC) and multi‐nucleated myotubule determination. The lifespan of primary myoblasts was 70 population doublings before entering into senescent state, with a population time of 18–24 hrs. Hence, we have developed a protocol for isolating human foetal primary myoblasts with excellent differentiation potential and robust growth and longevity. They should be useful for cell‐based therapy in human clinical applications with microencapsulation technology.
Early homing of adult mesenchymal stem cells in normal and infarcted isolated beating hearts
Authors: Penna Claudia , Raimondo Stefania , Ronchi Giulia , Rastaldo Raffaella , Mancardi Daniele , Cappello Sandra , Losano Gianni , Geuna Stefano , Pagliaro Pasquale
Published: September 2007

Little is known on the early homing features of transplanted mesenchymal stem cells (MSCs). We used the isolated rat heart model to study the homing of MSCs injected in the ventricular wall of a beating heart. In this model all types of cells and matrix elements with their interactions are represented, while external interferences by endothelial/neutrophil interaction and neurohormonal factors are excluded. We studied the morphology and marker expression of MSCs implanted in normal hearts and in the border‐zone of infarcted myocardium. Early morphological adaptation of MSC homing differs between normal and infarcted hearts over the first 6 hrs after transplantation. In normal hearts, MSCs migrate very early through the interstitial milieu and begin to show morphological changes. Yet, in infarcted hearts MSCs remain in the site of injection forming clusters of round‐shaped cells in the border‐zone of the infarcted area. Both in normal and infarcted hearts, immuno‐histochemistry and confocal imaging showed that, besides the proliferative marker proliferating cell nuclear agent (PCNA), some transplanted cells early express myoblastic maker GATA‐4, and some of them show a VWF immunopositivity. Moreover, a few hours after injection connexin‐43 is well evident between cardiomy‐ocytes and injected cells. This study indicates for the first time that the isolated beating heart is a good model to study early features of MSC homing without external interferences. The results show (i) that MSCs start to change marker expression few hours after injection into a beating heart and (ii) that infarcted myocardium influences transplanted MSC morphology and mobility within the heart.
Mosaicism in von Hippel‐Lindau disease: an event important to recognize
Authors: Santarpia Libero , Sarlis Nicholas J. , Santarpia Mariacarmela , Sherman Steven I. , Trimarchi Francesco , Benvenga Salvatore
Published: September 2007

von Hippel‐Lindau disease (VHL) is an autosomal dominant, familial neoplastic disorder with variable interfamilial and intrafamilial expression. VHL is characterized by pre‐disposition to development of a combination of benign and malignant tumours affecting multiple organs. We provide molecular evidence of somatic mosaicism in nearly asymptomatic man whose daughter had VHL. The mosaic subject was found to have a cyst of the kidney and an angioma of the glans penis and had had surgery for a mandibular cyst and epididymal cystadenomas. Mosaicism could provide a genetic explanation for the clinical heterogeneity and variable severity of VHL. The real incidence of mosaicism is still unclear and the identification of mosaicism has important consequences in genetic counseling of VHL patients who appear to have de novo VHL mutations and should be considered when evaluating patients with isolated VHL‐related tumours. Our results strongly suggest a complete and extensive clinical examination in the parents of each patient affected by an apparently de novo VHL germline mutation.We recommend performing a mutation screening of both parents of a proband with techniques that permit detection of low percentages of mosaicism before concluding that the proband has a de novo VHL mutation.
Mammary‐type fibroepithelial neoplasms of the vulva: a case report and review of the literature
Authors: Carter James Elliot , Mizell Kelly N. , Tucker Joseph Allan
Published: September 2007

Mammary‐type fibroepithelial neoplasms of the vulva are rare lesions of uncertain histogenesis. Origin from ectopic breast tissue and from anogenital glandular tissue that shares similar histologic homology with breast tissue has been postulated. We report the case of a 45‐year‐old woman who presented with a vulvar mass of several years duration. Excision of the lesion and subsequent histologic examination showed a mammary‐type fibroadenoma with apocrine change. No ectopic breast tissue was identified outside the lesion. The theories of histogenesis of these neoplasms and additional cases of mammary‐type lesions of the vulva reported in the medical literature are reviewed.
Nodular vasculitis – a novel cutaneous manifestation of autoimmune colitis
Authors: Pozdnyakova Olga , Garg Amit , Mahalingam Meera
Published: September 2007

Panniculitis in association with autoimmune colitis (AC) is mostly confined to reports of erythema nodosum (EN) and Crohn’s disease. We expand the repertoire of panniculitides associated with autoimmune bowel disease through a unique case report of nodular vasculitis (NV) that developed in parallel fashion to flares of ulcerative colitis (UC). A 51‐year‐old woman with a clinical history of surgically treated UC developed lesions on the lower legs that were initially diagnosed and treated as EN. Two years later, during a clinical exacerbation of UC, she developed similar lesions that on biopsy examination showed features consistent with NV. While treatment with antibiotics resulted in amelioration of both bowel symptoms and leg lesions, cessation of the same resulted in recurrence of both. This report implies an association between NV and UC.
Comparative study of histopathological and immunohistochemical findings in skin biopsies from patients with psoriasis before and after treatment with acitretin
Authors: Werner Betina , Bresch Martina , Brenner Fabiane Mulinari , Lima Hermenio Cavalcante
Published: September 2007

Background:  Acitretin has been shown to be effective for psoriasis treatment. Its mechanism of action is not completely understood, and there are few studies focusing on histological and immunohistochemical differences before and after treatment of psoriasis with acitretin.

Methods:  This is a prospective study of 17 patients with plaque psoriasis treated with acitretin for 4 months with biopsies taken before and after therapy. Histological features and immunohistochemical reactions to cytokeratin (CK) 10, CK16, CK19, Ki67 and CD1a were evaluated and compared.

Results:  There were nine men and eight women with median age of 47 years. Epidermal thickness, CK16 positivity, Ki67 and CD1a‐positive cell index reduced after treatment (p < 0.01). Suprapapillary plate thickness stayed the same (p > 0.05) although the epidermal/suprapapillary thickness ratio was significantly higher before treatment (p < 0.01). CK10 positivity was lower and a thicker basal cell layer was seen in the epidermis before treatment (p < 0.01). CK19 was negative in all cases.

Conclusions:  Acitretin therapy improved histological and immunohistochemical features typical of psoriasis. In psoriasis, suprapapillary plates are not thin, but the epidermal/suprapapillary thickness ratio is increased. Basal cell layer is expanded in psoriasis. Langerhans’ cells were less frequent after treatment, and that finding has to be investigated further to determine its role in acitretin mechanism of action.
Epithelioid sarcoma with angiomatoid features: report of an unusual case arising in an elderly patient within a burn scar
Authors: Kaddu Steven , Wolf Ingrid , Horn Michael , Kerl Helmut
Published: September 2007

Epithelioid sarcoma (ES) is a rare, aggressive soft tissue tumor with a characteristic predilection for adolescents and young adults, and a tendency to occur on distal extremities. We report a case of ES arising in an 80‐year‐old woman within a burn scar that histopathologically showed unusual ‘angiomatoid’ features. The patient presented initially with a solitary nodule on her right wrist arising at the site of a burn scar. Histopathologically, the tumor was composed of a proliferation of relatively bland, epithelioid and spindle cells focally arranged in a nodular pattern around areas of ‘geographic’ necrosis. In addition, there were prominent foci of hemorrhage and blood‐filled spaces as well as tumor cells with intracytoplasmic vacuoles, features suggestive of an angiomatous process. Immunohistochemistry showed positivity of tumor cells for cytokeratins and epithelial membrane antigen (EMA) whereas all vascular markers tested were negative. The overall histopathologic features were consistent with a diagnosis of ES. Follow up showed multiple recurrences arising proximally along the right upper extremity. Our case underlines the clinical and histopathological heterogeneity of ES, emphasizing the unusual occurrence of ES with ‘angiomatoid’ features in the elderly. In this uncommon setting, this tumor should be especially distinguished from epithelioid hemangioendothelioma and epithelioid angiosarcoma. The significance of development of ES on a healed burn scar is uncertain, but may suggest a possible causal relationship.
Solid apocrine carcinoma of the skin: report of a rare adnexal neoplasm mimicking lobular breast carcinoma
Authors: Zelger Bettina G. , Stelzmueller Ingrid , Dunst Karin M. , Zelger Bernhard
Published: September 2007

The so called ‘sweat gland carcinoma’ is a rare skin malignancy. The differentiation between apocrine and eccrine neoplasms remains difficult. Skin tumors of the axilla are often suspected to be metastasis of other neoplasms in particular breast cancer. A 71‐year‐old man presented with a morphea‐like plaque of the right axilla which in punch biopsy was first suspected as metastasis of primary lobular breast carcinoma. After further clinical and laboratory work up including immunohistochemistry the original diagnosis of a breast cancer had to be changed to solid apocrine carcinoma of the skin. Wide excision with en‐bloc axillary lymph node dissection was performed. Final tumor stage was pT2 N0 M0 (V0 L0). No adjuvant treatment was necessary, and there is no evidence of disease after 3 years. Solid apocrine carcinoma of the skin is a rare variant with apocrine differentiation. A survey of the stereotypical presentation of this lesion and a comparison with lobular breast carcinoma and other types of apocrine carcinoma of the skin is given.
Squamous cell carcinomas with single cell infiltration: a potential diagnostic pitfall and the utility of MNF116 and p63
Authors: Ko Christine J. , McNiff Jennifer M. , Glusac Earl J.
Published: September 2007

Numerous variants of squamous cell carcinoma (SCC) have been described. We recently encountered four examples of SCC composed primarily of single, atypical cells that were cytokeratin (CK) MNF116‐positive and p63‐positive. One case was particularly difficult to diagnose as the single cells were obscured by a dense inflammatory infiltrate. We have also noted similar single cell infiltration toward the periphery of four additional cases of more typical SCC. These foci resemble the single tumor cells that may infiltrate at the borders of spindle cell and desmoplastic SCCs. CK MNF116 and p63 were useful in identifying each of these neoplasms. This single – cell pattern of SCC can easily be misdiagnosed, and CK MNF116 and/or p63 are diagnostically helpful in recognizing it.
Ber‐EP4 enhances the differential diagnostic accuracy of cytokeratin 7 in pagetoid cutaneous neoplasms
Authors: Sellheyer Klaus , Krahl Dieter
Published: September 2007

Background:  While cytokeratin 7 is a reliable marker for most cases of Paget’s disease, it is not 100% sensitive. Moreover, cases of cytokeratin 7‐positive pagetoid squamous cell carcinoma in situ are reported in the literature. The monoclonal antibody Ber‐EP4 is diagnostically highly reliable in the differentiation between basal cell carcinoma and cutaneous squamous cell carcinoma. Here we report its application in the differential diagnosis of cutaneous pagetoid neoplasms.

Methods:  Biopsy samples from 21 cases of extramammary Paget’s disease, 12 pagetoid squamous cell carcinomas in situ and 10 pagetoid melanomas in situ of the superficial spreading type were examined immunohistochemically with Ber‐EP4, 34βE12 and HMB‐45.

Results:  Ber‐EP4 selectively labeled all cases of extramammary Paget’s disease but none of the other pagetoid neoplasms. The majority of cases (18 = 85.7%) displayed strong and three (14.3%) showed moderate immunoreactivity.

Conclusions:  Ber‐EP4 reliably differentiates extramammary Paget’s disease from pagetoid squamous cell carcinoma in situ and pagetoid melanoma in situ. The antibody should be included along with a panel of other markers when evaluating for pagetoid cutaneous neoplasms in order to avoid a possible misdiagnosis of pagetoid squamous cell carcinoma in situ.
Neue Aspekte zur Biographie Thomas Manns
Authors: Lehnert Herbert
Published: September 2007

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