bluuebunny/crossref_metadata_2025 huggingface dataset:
In situ splitting of a liver with middle hepatic vein anomaly
Authors: Genzone Alessandro , Al-Shurafa Haider , Mondello Rosalia , Morelli Nicola , Antonucci Adelmo , Valente Umberto , Andorno Enzo
Published: August 2002

In situ liver splitting provides a way to expand the graft pool, minimize cold ischemia time, and improve hemostasis at the cut surface of the graft. Vascular anomalies of the liver may make the splitting procedure very difficult or even impossible to perform. The in situ splitting procedure, performed on a liver with a middle hepatic vein (MHV) anomaly, is described here. The MHV drained directly into the segment III vein within the hepatic parenchyma instead of draining into the left hepatic vein to form the common trunk. In situ splitting was performed during multiorgan procurement from a 33-year-old man who died of isolated cerebral trauma. The MHV was reconstructed on the back table to secure right graft venous drainage using an iliac vein graft. The resultant right graft, segments I and IV to VIII, and left graft, segments II and III, were transplanted successfully into an adult and a child, respectively. The 2 transplant recipients are currently alive with normal hepatic function 20 months after transplantation.
Risk factors for acute rejection in pediatric living related liver transplantation: The impact of HLA matching
Authors: Sugawara Yasuhiko , Mizuta Koichi , Kawarasaki Hideo , Takayama Tadatoshi , Imamura Hiroshi , Makuuchi Masatoshi
Published: August 2002

The influence of HLA compatibility on acute rejection in cadaveric liver transplantation is not clearly defined, and that in living related liver transplantation (LRLT) has only been poorly examined. Few studies have focused solely on a pediatric population. Fifty-eight cases of pediatric LRLT were analyzed. Patient and graft survival rates and postoperative complications were assessed. The relationship between the incidence of acute rejection and HLA matching and some preoperative and intraoperative transplant recipient factors, including age, preoperative aspartate aminotransferase level, total bilirubin level, prothrombin time, ascites, donor-recipient blood group type and sex match, donor age, surgical time, anhepatic phase duration, volume of blood loss, and graft weight to standard liver volume, was examined. Patients with HLA-A zero mismatching (P = .04) or a greater volume of blood loss per body weight (P = .004) had a significantly lower chance of rejection within 6 weeks after LRLT. Our results show that in LRLT, a graft from an HLA-A zero-mismatched donor may be advantageous because it provides a lower chance of early acute rejection.
Temporary portocaval shunt during liver transplantation with vena cava preservation. Results of a prospective randomized study
Authors: Figueras Juan , Llado Laura , Ramos Emilio , Jaurrieta Eduardo , Rafecas Antonio , Fabregat Juan , Torras Jaume , Sabate Antonio , Dalmau Antonia
Published: August 2002

This study aims to determine whether the use of a temporary portocaval shunt (PCS) improves hemodynamic and metabolic evolution during orthotopic liver transplantation (OLT). Preservation of the vena cava during OLT has gained wide acceptance. However, benefits of adding a temporary PCS to the piggyback technique during the anhepatic phase in patients with cirrhosis have not been shown. Eighty patients with cirrhosis were studied prospectively. They were randomly distributed into two groups: patients with a temporary PCS (n = 40) and those without a PCS (n = 40). In all cases, the piggyback technique was used. Hemodynamic profiles and biochemical data during OLT and clinical evolution after OLT were evaluated. Preoperative data were similar in both groups. Surgical time also was similar (403 ± 77 v 387 ± 56 minutes; P = .3). Red blood cell requirements were lower in the PCS group (2.3 ± 2.5 v 3.3 ± 2.9 units), although differences were not significant. In the PCS group, 45% of patients did not need red blood cell transfusion, whereas in the other group, only 22% were not administered a transfusion (P = .03). During the anhepatic phase, the decrease in cardiac output was lower in the PCS group (−9.6% v −19%; P = .05), whereas diuresis during the anhepatic phase was greater in the PCS group (3.6 ± 2.97 v 2.1 ± 1.38 mL/kg/h; P = .005). There were no differences in liver biochemical parameters during the first 3 postoperative days. Nevertheless, creatinine levels increased significantly during this period only in the no-PCS group. The use of a temporary PCS during OLT improves hemodynamic status, reduces intraoperative transfusion requirements, and preserves renal function during and after OLT.
Management of the pediatric liver transplant patient
Authors: McDiarmid Sue V.
Published: August 2002

Key Points
De novo malignancies after liver transplantation: A major cause of late death
Authors: Fung John J. , Jain Ashok , Kwak E. J. , Kusne Shimon , Dvorchik Igor , Eghtesad Bijan
Published: August 2002

Key Points
The relevance of anxiety, depression, and coping in patients after liver transplantation
Authors: Nickel Ralf , Wunsch Andreas , Egle Ulrich T. , Lohse Ansgar W. , Otto Gerd
Published: August 2002

The aim of this study is to investigate the effects of anxiety, depression, and coping on quality of life in patients after liver transplantation. Patients were asked to fill out a postal survey. Two hundred thirty-six of 375 patients (63%) who entered the study returned the questionnaires, and 186 of these patients could be included in the assessment. Anxiety and depression were surveyed using the Hospital Anxiety and Depression Scale; health-related quality of life, using the 36-Item Short-Form Health Survey; and coping strategies, using the Freiburg Questionnaire on Coping With Illness. In terms of physical and mental dimensions of health-related quality of life, psychosocial factors are far more relevant in liver transplant recipients than purely somatic factors, such as the number of posttransplantation complications or length of hospital stay. Through multiple regression analysis, we were able to account for 51% of the variance in the physical dimension of health-related quality of life and 58% of the variance in the mental dimension. Physical factors of depression, age, and employment and mental factors of anxiety and depression were significant for predicting health-related quality of life after liver transplantation. Depressive coping, anxiety, and depression, as well as aspects of the social environment, contribute considerably to determine well-being and health-related quality of life of patients after liver transplantation.
Outflow reconstruction in recipients of right liver graft from living donors
Authors: Sugawara Yasuhiko , Makuuchi Masatoshi , Imamura Hiroshi , Kaneko Junichi , Ohkubo Takao , Kokudo Norihiro
Published: August 2002

Right-lobe transplantation is now a commonly used procedure in living donor liver transplantation (LDLT) to adult recipients. However, the risk for outflow obstruction is still an issue in LDLT. The right hepatic vein (RHV) was anastomosed end to end to the graft hepatic vein without unfavorable tension on the anastomosis. The anterior wall of the recipient hepatic vein was incised longitudinally, and a V-shaped vein graft was patched to form a wide and long orifice. This new hepatic venoplasty was used in 14 adult patients who received right liver grafts and gave good results without stenosis of the hepatic venous anastomosis or other complications. Our new technique may be useful in recipients of a right liver graft when the recipient or graft RHV is not long enough.
Rapid improvement of autonomic and peripheral neuropathy after liver transplantation: A single case report
Authors: McDougall Alan John , Davies Leo , McCaughan Geoffrey William
Published: August 2002

Peripheral and autonomic neuropathies are known but often unrecognized associations of cirrhosis from any cause. The pathogenesis of these effects are ill understood. Liver transplantation has been shown to reverse autonomic manifestations, but little evidence exists for an effect on peripheral neuropathy. This case report documents improvement in peripheral and autonomic neuropathy in a 40-year-old man with hepatitis B virus-related cirrhosis. A return to normal neurophysiological function was seen within 9 months of successful liver transplantation, suggesting a metabolic, rather than a structural, cause of such changes in the peripheral nervous system.
Donor morbidity associated with right lobectomy for living donor liver transplantation to adult recipients: A systematic review
Authors: Beavers Kimberly L. , Sandler Robert S. , Shrestha Roshan
Published: August 2002

The aim if this study is to determine donor morbidity associated with right lobectomy for living donor liver transplantation (LDLT) to adult recipients through a systematic review of the published literature. Data sources were English-language reports on donor outcome after LDLT. MEDLINE (1995 to June 2001) was searched using the MeSH terms “living donors” and “liver transplantation.” Limits were set for human only and English language only. Bibliographies of retrieved references were cross-checked to identify additional reports; 211 reports were obtained. Population studies and consecutive and nonconsecutive series were included. All studies reported at least one of the following outcomes specific to living donors (LDs) of right hepatic lobes to adult recipients: surgical and hospital complications, length of hospital stay, readmissions, recovery time, return to predonation occupation, health-related quality of life, or mortality. Abstracts of relevant articles were reviewed independently using predetermined criteria, and appropriate articles were retrieved. Study design and results were summarized in evidence tables. Summary statistics of combined data were performed when possible. Twelve studies met the inclusion criteria. Data on donor morbidity associated with right lobectomy are limited. On the basis of reported data, morbidity associated with LD right lobectomy ranges from 0% to 67%. In conclusion, reported morbidity associated with right lobe donation for LDLT varies widely. Standardized definitions of morbidity and better methods for observing and measuring outcomes are necessary to understand and potentially improve morbidity. Future studies assessing LD outcomes should report donor outcome more explicitly.
Model for end-stage liver disease and Child-Turcotte-Pugh score as predictors of pretransplantation disease severity, posttransplantation outcome, and resource utilization in United Network for Organ Sharing status 2A patients
Authors: Brown Robert S. , Kumar Shiva K. , Russo Mark W. , Kinkhabwala Milan , Rudow Dianne L. , Harren Patricia , Lobritto Steven , Emond Jean C.
Published: August 2002

The Model for End-Stage Liver Disease (MELD) has been proposed as a replacement for the Child-Turcotte-Pugh (CTP) classification to stratify patients for prioritization for orthotopic liver transplantation (OLT). Improved classification of patients with decompensated cirrhosis might allow timely OLT before the development of life-threatening complications, reducing the number of critically ill patients listed as United Network for Organ Sharing (UNOS) status 2A at the time of OLT. We compared the ability of the MELD and CTP scores to predict pre-OLT disease severity, as well as outcome and resource utilization post-OLT. Data from 42 consecutive UNOS status 2A patients undergoing OLT at a single center were used to calculate MELD and CTP scores at the time of status 2A listing. Multivariate analysis was used to determine the relationship between these scores and pre-OLT disease severity measures, survival post-OLT, and measures of resource use post-OLT. The MELD was superior to CTP score in predicting pre-OLT requirements for mechanical ventilation and dialysis. Neither score correlated with the resource utilization parameters studied. Only two patients died within 3 months post-OLT; neither score was predictive of survival in this cohort. In summary, the MELD is superior to CTP score in estimating pre-OLT disease severity in UNOS status 2A patients and thus may help risk stratify status 2A or decompensated status 2B OLT candidates and optimize the timing of OLT. However, neither score correlated with resource use post-OLT in the strata of critically ill patients.
Utility of pulse oximetry in the detection of arterial hypoxemia in liver transplant candidates
Authors: Abrams Gary A. , Sanders Michael K. , Fallon Michael B.
Published: August 2002

Hepatopulmonary syndrome, arterial hypoxemia caused by intrapulmonary vasodilatation, occurs in approximately 10% of patients with cirrhosis. The severity of hypoxemia affects liver transplant candidacy and is associated with increased morbidity and mortality posttransplantation. Screening guidelines for detecting the presence of arterial hypoxemia do not exist. The aim of this study is to investigate the accuracy and utility of pulse oximetry in the detection of hypoxemia (Pao2 < 70 mm Hg) in patients with cirrhosis. Two hundred prospective liver transplant candidates were compared with 94 controls. Arterial oxyhemoglobin saturation was obtained by pulse oximetry (Spo2) and compared with simultaneous arterial blood gas (ABG) oxyhemoglobin values (Sao2; bias = the difference). Pao2, carboxyhemoglobin, methemoglobin, and routine clinical and biochemical parameters were investigated to account for the bias. Spo2 overestimated Sao2 in 98% of patients with cirrhosis (mean bias, 3.37%; range, −1% to 10%). Forty-four percent of patients with cirrhosis and controls had a bias of 4% or greater. No clinical or biochemical parameters of cirrhosis accounted for the overestimation of pulse oximetry. Twenty-five subjects with cirrhosis were hypoxemic, and an Spo2 of 97% or less showed a sensitivity of 96% and a positive likelihood ratio of 3.9 for detecting hypoxemia. An Spo2 of 94% or less detected all subjects with an arterial Pao2 less than 60 mm Hg. Pulse oximetry significantly overestimates arterial oxygenation, and the inaccuracy is not influenced by liver disease. Nevertheless, pulse oximetry can be a useful screening tool to detect arterial hypoxemia in patients with cirrhosis, but a higher threshold for obtaining an ABG must be used.
The potential role of bone marrow transplantation in augmenting donor-derived immunity to hepatitis B after rat liver transplantation
Authors: Li Jun , Dahmen Uta , Dirsch Olaf R. , Gu YanLi , Polywka Susanne , Fiedler Melanie , Doebel Lothar , Roggendorf Michael , Broelsch Christoph Erich
Published: August 2002

Adoptive transfer of immunity to hepatitis B virus (HBV) is not provoked solely by bone marrow, but also by liver transplantation, although transiently. In the current study, simultaneous bone marrow transplantation, which possibly can increase the number of antibody-secreting cells, was performed to augment the efficacy of transferring HBV immunity. Stimulation of donor-derived immune cells by postoperative vaccination was used to investigate whether a secondary immune response can be induced in recipients. Orthotopic liver transplantation (n = 28), performed in three rat strain combinations representing different genetic constellations, was compared with bone marrow-augmented liver transplantation (n = 21). Donors had been vaccinated twice with recombinant hepatitis B surface antigen (HBsAg). Recipients surviving more than 10 weeks received a boost vaccination. All animals were monitored weekly for the presence of antibodies to HBsAg (anti-HBs). Effective anti-HBs titers were measured in 82% of liver recipients (23 of 28 recipients) and lasted from 2 to 9 weeks. Ninety percent of bone marrow-augmented liver recipients (19 of 21 recipients) seroconverted, with anti-HBs persisting from 2 to 12 weeks. A greater seroconversion rate, prolonged titer duration, and different pattern of titer development were observed in bone marrow-augmented liver recipients, although statistical significance could not be obtained because of the small numbers of comparable animals. Posttransplantation vaccination in recipients of combined grafts did not arouse a typical secondary antibody response, but showed a tendency toward an earlier and stronger response to vaccine in comparison to recipients without immune transfer. Simultaneous bone marrow transplantation showed an augmenting, but limited, effect on humoral immune transfer. Therefore, other potentially promising cellular strategies, such as transfer of in vivo and ex vivo stimulated antigen-specific cells should be pursued further. Improvement of the effect of postoperative vaccination possibly can be achieved by optimizing the immunization protocol.
Monitoring extracellular concentrations of lactate, glutamate, and glycerol by in vivo microdialysis in the brain during liver transplantation in acute liver failure
Authors: Tofteng Flemming , Larsen Fin Stolze
Published: August 2002

Swelling of cerebral glial cells is a characteristic complication in patients with acute liver failure (ALF). This astrocyte edema may result in high intracranial pressure (ICP) and brain herniation before or during liver transplantation. Metabolic alterations responsible for the development of high ICP in patients with ALF are not fully understood. We describe changes in neurochemistry during liver transplantation using a cerebral microdialysis technique in a young man with severe ALF and cerebral edema. We found that the extracellular content of lactate ([lactate]ec) gradually increased during the operation. Becauce cerebral oxygen saturation and [lactate]ec to [pyruvate]ec ratio were within normal limits, hypoxia was not likely to be responsible for the increased [lactate]ec levels. Instead, we found that [lactate]ec levels correlated in this patient with arterial lactate concentrations during and after grafting (r
2 = 0.96; P < .05), but did not correlate with arterial glucose concentrations (r
2 = 0.20; P = not significant). Also, [glutamate]ec and [glycerol]ec levels were severely elevated before liver transplantation, but tended to decrease in the hours after grafting. These findings indicate disturbances in glutamate neurotransmission, arachidonic acid metabolism, and lactate flux across the blood-brain barrier in patients with ALF.
Hepatic artery reconstruction and biliary stricture formation after living donor adult liver transplantation using the left lobe
Authors: Suehiro Taketoshi , Ninomiya Mizuki , Shiotani Satoko , Hiroshige Syoji , Harada Noboru , Ryosuke Minagawa , Soejima Yuji , Shimada Mitsuo , Sugimachi Keizo
Published: August 2002

Biliary complications, including bile leak, biliary stricture, and cholangitis, are seen in 15% to 29% of all cases after living related liver transplantation. We investigate risk factors and discuss the management of biliary complications after living related liver transplantation in adults using left-lobe grafts. We studied 37 adult patients who underwent living related liver transplantation using left-lobe grafts. Perioperative variables were evaluated as risk factors for biliary strictures. The overall incidence of biliary complications was 43.2% (16 of 37 patients). Anastomotic strictures occurred in 8 patients, whereas bile leaks and cholangitis occurred in 9 and 8 patients, respectively. Anastomotic stricture was strongly related to a partial artery reconstruction (P < .02) and cholangitis (P < .01). Anastomotic biliary stricture was not associated with bile leak, acute cellular rejection, or infection. Our results suggest that an important risk factor for biliary anastomotic biliary strictures is a partial artery reconstruction. To minimize the risk for biliary anastomotic strictures, we will reconstruct both the middle and left hepatic artery.
Vertical portal vein clamping in right hepatic lobectomy for live donation or neoplasm
Authors: Yanaga Katsuhiko , Kamohara Yukio , Takatsuki Mitsuhisa , Furui Junichiro , Kanematsu Takashi
Published: August 2002

A modified technique is described in clamping the right branch of the portal vein in right hepatic lobectomy for live donation or neoplasm that allows flush division of the origin of the right branch without causing portal vein stenosis.
Metabolic, cardiovascular, and acid-base status after hepatic artery or portal vein reperfusion during orthotopic liver transplantation
Authors: Walsh Timothy S. , Garden James O. , Lee Alistair
Published: August 2002

During liver transplantation, reperfusion traditionally is performed through the portal vein. After anecdotal observations that patients who underwent reperfusion first through the hepatic artery were more hemodynamically stable, we performed an exploratory, prospective, observational, nonrandomized study to compare cardiovascular stability, acid-base status, and metabolic gas exchange between patients who underwent reperfusion through either the portal vein or hepatic artery. We studied 20 patients undergoing liver transplantation (10 patients, reperfusion first through the portal vein; 10 patients, reperfusion first through the hepatic artery). Cardiovascular and acid-base parameters were compared at times before and after anastomosis of each vessel, and epinephrine use was recorded. Oxygen consumption (Vo2) and carbon dioxide elimination (Vco2) were measured continuously by using an indirect calorimeter. Alanine aminotransferase (ALT) concentrations 24 hours after transplantation were compared as an index of reperfusion injury. Cardiovascular changes (mean arterial pressure, cardiac output) were similar for both groups, but more epinephrine was administered to the portal-vein group (P = .014). There was a greater increase in Paco2 after portal reperfusion (median portal vein, 1.01 kPa; hepatic artery, 0.29 kPa; P = .015) and a trend toward more severe acidemia. Vo2 increased more rapidly in the portal-vein group (P = .005), but overall changes in Vo2 during the study period were similar. There were no differences in Vco2 between the groups or ALT concentrations 24 hours posttransplantation. These observational data suggest that hepatic arterial reperfusion may be associated with reduced epinephrine requirements and a slower rate of acid release, which could be advantageous in unstable patients. Vo2 increases more slowly after hepatic artery reperfusion, which could indicate slower reoxygenation of the graft. Further studies of the relative merits of each technique are warranted.
Successful hepatitis B vaccination in patients who underwent transplantation for hepatitis B virus-related cirrhosis: Preliminary results
Authors: Bienzle Ulrich , Günther Matthias , Neuhaus Ruth , Neuhaus Peter
Published: August 2002

Long-term hepatitis B immunoglobulin (HBIg) prophylaxis prevents endogenous hepatitis B virus (HBV) reinfection in the majority of liver transplant recipients. Active hepatitis B vaccination after orthotopic liver transplantation (OLT) in these patients has produced conflicting results to date. On this study, patients who remained hepatitis B surface antigen (HBsAg) negative with passive immunization after OLT for HBV cirrhosis were actively immunized using recombinant HBV antigen (Engerix), together with a novel adjuvant system (monophosphoryl lipid A and a natural saponine molecule). This led to a sustained antibody response to HBsAg (>500 IU/L) in 5 of 10 patients. This antibody response prevented reinfection and allowed termination of prophylactic HBIg substitution for more than 12 months in these patients.
In Vitro Evaluation of Antibiotic Elution from Polymethylmethacrylate (PMMA) and Mechanical Assessment of Antibiotic‐PMMA Composites
Authors: Weisman Debra L. , Olmstead Marvin L. , Kowalski Joseph J.
Published: August 2002

Objective—To determine whether different methods of sterilization of antibiotic vials or the heat of polymerization altered the antimicrobial activity or mechanical properties of antibiotic/polymethylmethacrylate (PMMA) composites when compared to antibiotic‐free PMMA.

Study Design—In vitro study.

Methods—Steam‐sterilized, gas‐sterilized, and non‐sterilized 1 gram vials of cefazolin and injectable gentamicin sulfate (high and low doses) were mixed with PMMA to prepare composites for antibiotic elution evaluation, compression, and elongation testing. Blocks of PMMA that contained antibiotic were assayed for antibacterial activity using an agar gel diffusion method or were placed in phosphate buffered saline (PBS) to assess elution of antibiotic. Phosphate buffered saline samples from steam‐sterilized cefazolin and high‐dose gentamicin groups were assayed on days 1, 2, 5, and 9 for cefazolin or gentamicin concentration by high‐pressure liquid chromatography or fluorescent polarization immunoassay, respectively.

Results—Pmma blocks containing antibiotic inhibited bacterial growth of Staphylococus aureus 25923 for an average of 9 days. Cefazolin and gentamicin concentration in PBS decreased dramatically after the first 24 hours, but remained above minimum inhibitory concentration (MIC) throughout the experiment for all groups except low‐dose gentamicin. Compressive strength of plugs made from plain cement and plugs made from PMMA mixed with untreated and steam‐sterilized cefazolin was similar, but was significantly different from the other groups. There appeared to be an inverse relationship between compressive strength and elongation.

Conclusion—PMMA/antibiotic composites inhibited bacterial growth for 7 to 10 days. Compressive strength was affected by different additions of antibiotic.

Clinical Relevance—Bacteria introduced during a surgical procedure may be inhibited by elution of antibiotic from PMMA at the time of contamination.
Hemostatic Profiles in 39 Dogs With Congenital Portosystemic Shunts
Authors: Niles Jacqui D. , Williams John M. , Cripps Peter J.
Published: August 2002

Objectives— To determine if there were significant changes in prothrombin time (PT), partial thromboplastin time (PTT), and fibrinogen levels in dogs with naturally occurring congenital portosystemic shunts (CPSS) and to determine if there was any association between these values, serum albumin concentration, and the ability to attenuate the shunt vessel.

Study Design— Retrospective clinical study.

Animals— Thirty‐nine client‐owned dogs.

Methods— Medical records of 60 dogs with confirmed CPSS were retrospectively evaluated. Hemostatic profiles had been performed before surgery in 39 cases.

Results— Dogs with CPSS had significantly higher values for PTT ( P < .001) when compared with normal dogs. Of the total number of dogs, 64.1% had a PTT greater than 16 seconds (25/39). PTT was prolonged by 25% or more in 51.3% of dogs (20/39). PT tended to be higher in dogs with CPSS (

P= .036), although only 7.7% (3/39) of dogs had a PT greater than 12 seconds (the maximum reference value). Dogs with CPSS had significantly lower values for albumin and fibrinogen (

P<.001). Platelet numbers were within the normal range in 87.2% of cases (34/39). Of the 5 dogs with platelet numbers outside the normal range, 3 were mildly thrombocytopenic. Fibrin degradation product concentrations were not elevated in any dogs tested (

N = 22). There was no significant difference in any of the measured variables between dogs with extrahepatic shunts and those with intrahepatic shunts (

P >.1). For PT, PTT, albumin, and fibrinogen, there was no significant difference between dogs that underwent total, partial, or no attenuation (

P > .3).

Conclusions— Dogs with CPSS have a tendency to have a prolonged PTT. There was no significant difference in hemostatic profile results between dogs with intrahepatic shunts versus extrahepatic shunts. Preoperative hemostatic profile abnormalities were not useful as predictors of ability to attenuate CPSS.

Clinical Relevance— Prolonged PTT was not associated with bleeding tendencies in any of the dogs. Assays of individual clotting factors may help to further characterize the abnormalities present in animals with CPSS and may identify specific factor deficiencies. This might enable identification of a noninvasive diagnostic or prognostic indicator.
A New Mathematical Model for Assessing Therapeutic Strategies for HIV Infection
Authors: Gumel A. B. , Zhang Xue-Wu , Shivakumar P. N. , Garba M. L. , Sahai B. M.
Published: August 2002

The requirements for the eradication of HIV in infected individuals are unknown. Intermittent administration of the immune activator interleukin‐2 (IL‐2) in combination with highly‐active antiretroviral therapy (HAART) has been suggested as an effective strategy to realize long‐term control of HIV replication in vivo. However, potential latent virus reservoirs are considered to be a major impediment in achieving this goal. In this paper, a new mathematical model is designed and used to monitor the interactions between HIV, CD4+ T‐cells, CD8+ T‐cells, productively infected and latently infected CD4+ T‐cells, and to evaluate therapeutic strategies during the first 3 years of HIV infection. The model shows that current anti‐HIV therapies, including intermittent IL‐2 and HAART, are insufficient in achieving eradication of HIV. However, it suggests that the HIV eradication may indeed be theoretically feasible if such therapy is administered continuously (without interruption) under some specified conditions. These conditions may realistically be achieved using an agent (such as a putative anti‐HIV vaccine) that brings about a concomitant increase in the proliferation of HIVspecific CD4+ T‐ and CD8+ T‐cells and the differentiation of CD8+ T‐cells into anti‐HIV cytotoxic T lymphocytes (CTLs).
Polymyositis, Topological Proteomics Technology and Paradigm for Cell Invasion Dynamics
Authors: Schubert Walter
Published: August 2002

Polymyositis is an inflammatory myopathy characterized by muscle invasion of T‐cells penetrating the basal lamina and displacing the plasma membrane of normal muscle fibers. This investigation presents a technology for the direct mapping of protein networks involved in T‐cell invasion in situ. Simultaneous localization of 17 adhesive cell surface receptors reveals 18 different combinatorial expression patterns (CEP), which are unique for the T‐cell invasion process in muscle tissue. Each invasion step can be assigned to specific CEP on the surface of individual T‐cells. This indicates, that the T‐cell invasion is enciphered combinatorially in the T‐cells′ adhesive cell surface proteome fraction. Given 217 possible combinations, the T‐cell appears to have at its disposal a highly non‐random restricted repertoire to specify migratory pathways at the cell surface. These higher‐level order functions in the cellular proteome cannot be detected by large‐scale protein profiling techniques from tissue homogenates. High‐throughput whole cell mapping machines working on structurally intact tissues, as shown here, will allow to measure how cells of different origin (immune cells, tumor cells) combine cell surface receptors to encipher specificity and selectivity for interactions.
Breast Cancer: Modelling and Detection
Authors: Gavaghan D. J. , Brady J. M. , Behrenbruch C. P. , Highnam R. P. , Maini P. K.
Published: August 2002

This paper reviews a number of the mathematical models used in cancer modelling and then chooses a specific cancer, breast carcinoma, to illustrate how the modelling can be used in aiding detection. We then discuss mathematical models that underpin mammographic image analysis, which complements models of tumour growth and facilitates diagnosis and treatment of cancer. Mammographic images are notoriously difficult to interpret, and we give an overview of the primary image enhancement technologies that have been introduced, before focusing on a more detailed description of some of our own recent work on the use of physics‐based modelling in mammography. This theoretical approach to image analysis yields a wealth of information that could be incorporated into the mathematical models, and we conclude by describing how current mathematical models might be enhanced by use of this information, and how these models in turn will help to meet some of the major challenges in cancer detection.
An Embedded Low Transistor Count 8‐bit Analog‐to‐digital Converter Using a Binary Searching Method
Authors: Wang Chua-Chin , Hsueh Ya-Hsin , Huang Shao-Ku
Published: August 2002

Small analog‐to‐digital converter (ADCs) are very popular when they are required in many interfaces or system designs. Ever since the system‐on‐chip (SOC) became one of the major trends in chip designs, the demand for small and less power draining ADCs has urgently emerged. The area factor is particularly critical when it comes to the cost issue. In this paper, a small but stable ADC intellectual property (IP) macro design is proposed wherein a binary search scheme is utilized to produce the ADC function. A total of eight cycles are needed to convert the analog signal based upon simulation results. A physical chip is fabricated to verify the correctness of our design.
Lutropin Receptor Function: Insights from Natural, Engineered, and Computer‐Simulated Mutations
Authors: Fanelli Francesca , Themmen Axel P. N. , Puett David
Published: August 2002

The lutropin receptor is a member of the superfamily of G protein‐coupled receptors and, in humans, binds two closely related ligands, members of the heterodimer glycoprotein hormone family. As reviewed herein, comparative analyses of natural, engineered, and computer‐simulated mutations of the lutropin receptor have provided considerable insight into the molecular basis of receptor function.
VEGF Receptor Signaling and Endothelial Function
Authors: Kliche Stefanie , Waltenberger Johannes
Published: August 2002

Angiogenesis, the formation of new blood vessels from preexisting ones, is a central process during normal development and during pathological repair. Vascular endothelial growth factor‐A (VEGF‐A) can stimulate both physiological and pathological angiogensis. VEGF‐A is a ligand for the two receptor tyrosine kinases VEGFR‐1 (Flt‐1) and VEGFR‐2 (KDR/Flk‐1). Most biological functions of VEGF‐A are mediated via VEGFR‐2, whereas the role of VEGFR‐1 is largely unknown. Activation of mitogenactivated kinase, stress‐activated kinase, protein kinase C, and the Akt pathway are implicated in VEGF‐A‐dependent endothelial function, including cell survival, proliferation, generation of nitric oxide, and the induction of angiogenesis. Induction of metalloproteinases, activation of focal adhesion kinase and of PI3‐kinase are implicated in VEGF‐A‐induced endothelial cell migration. The important role of nitric oxide as a mediator of endothelial function in vivo links the receptor signaling network to other biological effects.
Effects of Metal Substitution on Third-order Optical Non-linearity of Porphyrin Macrocycle
Authors: KANDASAMY K. , SHETTY SHANKAR J. , PUNTAMBEKAR P. N. , SRIVASTAVA T. S. , KUNDU T. , SINGH BHANU P.
Published: August 2002

The effects of axial ligands in Sn ( IV )-substituted 5,10,15,20-tetrakis [4-(carboethoxymethyleneoxy)phenyl]porphyrin and divalent transition metal substitution in 5,10,15,20-tetraphenylporphyrin on the second molecular hyperpolarizability (γ) at 802 nm were studied using the Z-scan technique. A significant increase in γ for divalent metal ions is observed with decreasing d-shell occupancy. In the case of the tetravalent metal-substituted porphyrin a dramatic enhancement of γ is seen when a strongly electronegative axial ligand such as I2is attached to the metal ion. A plausible explanation for the observed trend of γ has been sought in terms of metal-ligand interaction.
The Gene Guessing Game
Authors: Dunham Ian
Published: August 2002

A recent flurry of publications and media attention has revived interest in the question of how many genes exist in the human genome. Here, I review the estimates and use genomic sequence data from human chromosomes 21 and 22 to establish my own prediction.
Comparison ofMycobacterium tuberculosisGenomes Reveals Frequent Deletions in a 20 kb Variable Region in Clinical Isolates
Authors: Ho Timothy B. L. , Robertson Brian D. , Taylor G. Michael , Shaw Rory J. , Young Douglas B.
Published: August 2002

TheMycobacterium tuberculosiscomplex is associated with a remarkably low level of structural gene polymorphism. As part of a search for alternative forms of genetic variation that may act as a source of biological diversity inM. tuberculosis, we have identified a region of the genome that is highly variable amongst a panel of unrelated clinical isolates. Fifteen of 24 isolates examined contained one or more copies of theM. tuberculosis-specific IS6110insertion element within this 20 kb variable region. In nine of the isolates, including the laboratory-passaged strain H37Rv, genomic deletions were identified, resulting in loss of between two and 13 genes. In each case, deletions were associated with the presence of a copy of the IS6110element. Absence of flanking tri- or tetra-nucleotide repeats identified homologous recombination between adjacent IS6110elements as the most likely mechanism of the deletion events. IS6110insertion into hot-spots within the genome ofM. tuberculosisprovides a mechanism for generation of genetic diversity involving a high frequency of insertions and deletions.
Measuring aggression: Self‐reports, partner reports, and responses to provoking scenarios
Authors: O’Connor Daryl B. , Archer John , Wu Frederick W.C.
Published: August 2002

This paper describes three studies. The first is concerned with the relationship between the Aggression Questionnaire (AQ) and a peer‐report version of the AQ (AQ‐P). The results (from a sample of 77 men aged 19 to 55 years) showed agreement between the two versions, thus providing evidence for the congruent validity of the AQ‐P, and good internal consistency was shown for the subscales of the AQ and AQ‐P. The second study involved the development, piloting, and validation of a vignette‐based assessment of aggressive behavior, the Aggressive Provocation Questionnaire. The third concerned the use of the finalised Aggressive Provocation Questionnaire in a sample of 130 men (aged 17 to 54 years). The results show that prior self‐reported aggression (measured by the AQ) predicted responses to provoking scenarios. Younger men (< 28 years) showed an association between physical aggression and the aggressive action scale (of the Aggressive Provocation Questionnaire) in response to provoking scenarios. Older men (> 28 years) showed an association between physical aggression and the assertive action scale. The findings are discussed in relation to aggression measurement and changes in aggression with age. Aggr. Behav. 27:79–101, 2001. © 2001 Wiley‐Liss, Inc.
Acquired von Willebrand disease—hemostatic management of major orthopedic surgery with high‐dose immunoglobulin, desmopressin, and continuous factor concentrate infusion
Authors: Frank Rolf Dario , Kunz Dagmar , Wirtz Dieter Christian
Published: August 2002

Acquired von Willebrand disease (aVWD) is a rare bleeding disorder that mimics congenital VWD in previously healthy individuals; it is most frequently associated with monoclonal gammopathy. Hemostatic therapy of aVWD is challenging due to the extremely shortened half‐life of endogenous and exogenous VWF. High‐dose intravenous immunoglobulin (ivIG) is recommended as the treatment of choice, usually rapidly normalizing coagulation; but in case of failure, alternative treatment options are not well explored. We report successful major orthopedic surgery in a 61‐year‐old woman with multiple myeloma IgG lambda and aVWD. IvIG alone failed to correct hemostasis. However, ivIG pretreatment improved the VWF ristocetin cofactor (VWF:RCo) half‐life from only 1.5 hr to more than 4 hr, allowing desmopressin infusions twice daily to maintain sufficient VWF:RCo levels. Because of diminishing desmopressin effect, we attempted for the first time in aVWD a continuous VWF/FVIII infusion (Haemate HS®, 2.1–2.7 FVIII U/kg/hr or 51–64 U/kg/day, respectively 4.6–6.0 VWF:RCo U/kg/hr or 110–145 U/kg/day) to reach constant factor levels. The steady‐state clearance was 2.4 mL/kg/hr for FVIII:C and 13.5 mL/kg/hr for VWF:RCo. During surgery, VWF:RCo, FVIII:C, and PFA‐100 closure time were normalized. Until day 5, VWF:RCo was kept above 50%, from day 6 to 10 at least 30% activity were attained. FVIII:C levels were always >70%. The clinical course was uneventful without bleeding. Two weeks after hip surgery the patient was discharged from the hospital without complaints. The therapy described can be recommended as safe and feasible for further evaluation in aVWD patients who are hyporesponsive to ivIG treatment alone. Continuous VWF/FVIII infusion can improve substitution therapy in aVWD. Am. J. Hematol. 70:64–71, 2002. © 2002 Wiley‐Liss, Inc.
CD34‐positive acute promyelocytic leukemia is associated with leukocytosis, microgranular/hypogranular morphology, expression of CD2 and bcr3 isoform
Authors: Foley R. , Soamboonsrup P. , Carter R.F. , Benger A. , Meyer R. , Walker I. , Wan Y. , Patterson W. , Orzel A. , Sunisloe L. , Leber B. , Neame P.B.
Published: August 2002

Acute promyelocytic leukemia (APL) has a favorable prognosis. Current therapy includes chemotherapy used in combination with all‐trans‐retinoic acid (ATRA). Although the differentiating effects of ATRA on promyelocytes have been well established, in vitro studies have shown that less‐differentiated APL blasts (CD34+) demonstrate a variable responsiveness to ATRA. To assess the clinical relevance of this finding, we analyzed a cohort of 38 patients with t(15;17) and/or PML‐RARα APL to determine the incidence and laboratory features of CD34+ APL. Thirty‐two percent (12/38) of cases were CD34+. There was a difference in WBC at presentation between CD34+ and CD34− cases (34.6 ± 9.2, mean ± standard error vs. 5.4 ± 2.0, P = 0.009). Patients with CD34+ APL demonstrated a micro/hypogranular phenotype (75%) (P = 0.001), co‐expression of CD2+ (83%) (P = 0.001), and the bcr3 isoform (100%) (P = 0.017). In contrast, CD34− cases demonstrated hypergranular morphology (65%), CD2+ (15%), and the bcr1 isoform (50%). A high presenting WBC count (\G10 × 109/L) was associated with an inferior overall survival (Log rank = 0.0047). Patients with CD34+ APL demonstrated an incidence of early mortality of 50%. Despite a marked correlation between CD34 positivity and increased WBC count, overall survival of CD34+ and CD34− cases did not differ significantly in our small cohort. Immunophenotypic analysis for CD34 expression should be included in future large APL trials to determine if detection of CD34+ blasts represents an independent adverse prognostic factor. Am. J. Hematol. 67:34–41, 2001. © 2001 Wiley‐Liss, Inc.
Extreme warfarin sensitivity in siblings associated with multiple cytochrome P450 polymorphisms
Authors: Tabrizi Arash Rafii , McGrath Sean D. , Blinder Morey A. , Buchman Timothy G. , Zehnbauer Barbara A. , Freeman Bradley D.
Published: August 2002

Warfarin use is complicated by an erratic dose response. Warfarin is metabolized by two distinct subfamilies of the cytochrome P450 (CYP) complex. We describe two siblings with extreme sensitivity to warfarin who share an unusual CYP genotype. These individuals illustrate both the importance of genetics in influencing the metabolism of warfarin as well as the potential utility of genetic testing as a guide to prescribing this medication. Am. J. Hematol. 67:144–146, 2001. © 2001 Wiley‐Liss, Inc.
Non‐anemic homozygous βo thalassemia in an African‐American family: Association of high fetal hemoglobin levels with β thalassemia alleles
Authors: Divoky Vladimir , Mrug Michal , Thornley‐Brown Denyse , Divoka Martina , Prchal Josef T.
Published: August 2002

We have studied a four‐generation (23 subjects) African‐American family with βo thalassemia and high fetal hemoglobin (HbF) levels. The βo thalassemia in this family is due to the splicing site mutation, β IVS2+1G→A, that leads to aberrant mRNA processing and the absence of β globin. Two members of this family are homozygous for βo thalassemia and are non‐anemic. All family members who are heterozygous for the β IVS2+1G→A mutation have elevated HbF, with the exception of two individuals who also have severe α‐globin chain deficiency. We excluded linkage with the hereditary persistence of fetal hemoglobin loci on chromosomes 6 and X. We also excluded the presence of all previously described determinants in the β globin gene cluster associated with elevated HbF production. One thalassemia allele is in the Cameroon‐like (HS2)/Benin‐like β globin gene cluster haplotype, and the other is in the Senegal‐like (HS2)/Benin‐like β globin gene cluster haplotype. We speculate that in the homozygotes, those erythroid cells that express low to absent levels of γ globin are selectively destroyed. In contrast, in the heterozygotes, the presence of the normal β globin allele would ameliorate the globin chain imbalance and thus allow survival of erythroid cells that express the abnormal transcript, leading to a typical βo thalassemia phenotype. Thus, the heterocellular γ globin expression together with in vivo preferential survival of HbF‐containing erythroid cells ameliorates Cooley's anemia in the βo thalassemia homozygotes. It remains to be determined what sequences linked to each thalassemia allele and what trans‐acting factors contribute to high HbF levels. Am. J. Hematol. 68:43–50, 2001. © 2001 Wiley‐Liss, Inc.
Re: Response to: Mortality among rubber chemical manufacturing workers by M.M. Prince et al. Am. J. Ind. Med. 2000. 37:590–598. I. Reply to Valentgas et al.'s letter to the editor
Authors: Prince Mary M. , Ward Elizabeth M. , Ruder Avima M. , Salvan Alberto , Roberts Dennis R.
Published: August 2002

We appreciate the opportunity to respond to comments by Valentgas and colleagues regarding our report examining mortality among rubber chemical manufacturing workers [Prince et al., 2001]. Following are our responses to their comments, focusing on the authors' main points:
Is it safe on deck? Fatal and non‐fatal workplace injuries among Alaskan commercial fishermen*
Authors: Thomas Timothy K. , Lincoln Jennifer M. , Husberg Bradley J. , Conway George A.
Published: August 2002

Background

Commercial fishing in Alaska accounts for an occupational fatality rate that is 28 times the rate for all U.S. workers. Most deaths are attributed to vessel sinking or capsizing. However, many deaths and most non‐fatal injuries are not related to vessel loss. This paper describes injuries that occur on the dock or on the fishing vessel.

Methods

Data from fishing fatalities and non‐fatal injuries between 1991–1998 were analyzed using the Alaska Occupational Injury Surveillance System and the Alaska Trauma Registry.

Results

There were 60 workplace deaths unrelated to vessel loss; most from falls overboard, others from trauma caused by equipment on deck. There were 574 hospitalized injuries, often from falls on deck, entanglement in machinery, or being struck by an object.

Fishing boats are hazardous working environments. Further efforts are required to prevent falls overboard and on deck, and to redesign or install safety features on fishing machinery and equipment. Am. J. Ind. Med. 40:693–702, 2001. Published 2001 Wiley‐Liss, Inc
Mica dust as a cause of severe pneumoconiosis
Authors: Zinman Carron , Richards Guy Anthony , Murray Jill , Phillips James Ian , Rees David John , Glyn‐Thomas Raymond
Published: August 2002

Background

Mica exposure is frequent in mines, mills, agriculture, construction, and industry. This is a case report of possible mica pneumoconiosis.

Methods

Case report and description of pathology. Histology slides were subjected to spectroscopic examination.

Results

Fibrosis in the presence of mica, without evidence of silica was confirmed.

Conclusions

This report indicates that mica exposure may result in mica pneumoconiosis. Am. J. Ind. Med. 41:139–144, 2002. © 2002 Wiley‐Liss, Inc.