bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk factors for cataract in Chinese patients with type 2 diabetes: evidence for the influence of the aldose reductase gene
Authors: Lee SC , Wang Y , Ko GTC , Ma RCW , Critchley JAJH , Cockram CS , Chan JCN
Published: March 2003

There is evidence that the development of retinopathy in type 2 diabetes is associated with a microsatellite polymorphism at 5′ of the aldose reductase gene. The study examined whether cataract was associated with clinical/metabolic factors and/or the microsatellite polymorphism using a cohort of consecutively recruited Hong Kong Chinese patients with type 2 diabetes (n=567). Amongst these patients, 157 (28%) had cataract. The patients with cataract were older in age and age at diagnosis and had longer diabetes duration than those without cataract (all at p<0.01). They also had higher systolic blood pressure (p<0.01), HbA1c (p<0.05) and fasting plasma glucose levels (p<0.01; all with adjustment for the significance). Moreover, we found that the patients with cataract over‐presented the microsatellite allele Z (23 vs. 30%, p<0.01) and its genotypes (Z,Z+Z,non‐Z; 38 vs. 50%, p<0.01), but under‐presented the allele Z−4 (8.3 vs 4.8%, p<0.05) and its genotypes (Z−4, Z−4+Z−4,non‐Z−4; 16 vs. 10%, p<0.05). Using multiple logistic regression analysis (R2=0.25, p<0.01), we found that the presence of cataract was correlated positively with age, but inversely with the presence of allele Z−4. In conclusion, our data indicate that the occurrence of cataract is common in the Chinese type 2 diabetes population, with age and the aldose reductase gene as important determinants.
Rett syndrome from quintuple and triple deletions within the MECP2 deletion hotspot region
Authors: Lebo RV , Ikuta T , Milunsky JM , Milunsky A
Published: March 2003

Rett syndrome results from mutations in the X‐linked methyl‐CpG‐binding protein 2 (MECP2) gene, which are nearly always lethal in males and lead to regression and reduced life expectancy in females. Herein we report one propositus with five tandem deletions and a second propositus with three tandem deletions within MECP2 exon 4 that encode truncated protein products resulting in classic Rett syndrome. These deletion breakpoints and single deletions in 3 other patients were all found within a 185‐bp region along with 64 of 69 other reported deletion breakpoints in the MECP2 gene. Illegitimate recombination resulting in deletion at a substantial proportion of the shared MECP2 sites is enhanced by repeated guanosine (G) DNA sequences in the antisense direction, consistent with reports at other gene loci that polypurine (multiple guanosine or adenosine (A)) basepairs enhance sequence deletion. Multiple deletions at the same poly G recombination sites confirm the existence of deletion hotspots in this gene region with numerous repeated antisense sites that are enriched 26‐ to 161‐fold. Deletion by illegitimate recombination within a single allele can occur during mitotic or meiotic cell cycles. Although prone to disease‐causing deletion, this region is unique in humans and highly conserved among mammals for the last 75 000 000 years to maintain the MECP2 gene's critical function.
Genetic heterogeneity in Korean families with autosomal‐dominant polycystic kidney disease (ADPKD): the first Asian report
Authors: Lee Jung Geon , Lee Kyu Beck , Kim Un Kyung , Ahn Curie , Hwang Dae Yeon , Hwang Young Hwan , Eo Hyun‐Seon , Lee Eun Joo , Kim Yon Su , Han Jin Suk , Kim Suhnggwon , Lee Jung Sang
Published: March 2003

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease in adults, and the prevalence of this disease within the chronic haemodialysis patient population is known to be approximately 2% in Korea. So far, three genetic locus have been identified as being responsible for ADPKD, and approximately 85% of the cases in Western countries are related to the PKD1 gene. However, little information is available concerning the pattern of linkage analysis in Asian populations.  Methods: 48 families with hereditary renal cysts were recruited by consent and their molecular genetic characteristics were studied. Linkage analysis was done with microsatellite markers (PKD1: SM7, UT581, AC2.5, KG8, D16S418; PKD2: D4S423, D4S1534, D4S1542, D4S1544, D4S2460). Genomic DNA polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis (PAGE) gel run were performed, and the resultant allele patterns were compared with sonographic findings.  Results: The results of this study showed that the ratio PKD1:PKD2 was 31:8, and that the PKD2 families exhibited a tendency toward a milder renal prognosis than the PKD1 families.  Conclusion: We confirmed the applicability of linkage analysis for ADPKD in the Korean population, and our data confirmed a similar incidence of PKD1 (79%) and PKD2 (21%) in Korean patients as in the Western population.
High incidence rate and absent family histories in one quarter of patients newly diagnosed with Huntington disease in British Columbia
Authors: Almqvist EW , Elterman DS , MacLeod PM , Hayden MR
Published: March 2003

The advent of the direct mutation test for Huntington disease (HD) has made it possible to identify a previously unrecognized symptomatic population of HD, including those with an atypical presentation or patients without a family history of HD. The present study investigated the uptake of this test in the province of British Columbia (BC), Canada and assessed the incidence rate and rate of identification of new mutations for HD. All symptomatic individuals residing in BC who were referred for the genetic test for HD between 1993 and 2000 (n=205) were analyzed for CAG expansion, baseline demographics and clinical data, and a family history of HD. A total of 141 (or 68.8%) had a CAG expansion ≥36. Of these, almost one‐quarter (24.1%) did not have a family history of HD. An extensive chart review revealed that 11 patients (or 7.8%) had reliable information on both parents (who lived well into old age) and therefore possibly could represent new mutations for HD. This indicates a three to four times higher new mutation rate than previously reported. Our findings also show that the yearly incidence rate for HD was 6.9 per million, which is two times higher than previous incidence studies performed prior to the identification of the HD mutation. We also identified five persons with a clinical presentation of HD but without CAG expansion (genocopies) (2.4%).
Comparative analysis of isodisomic and heterodisomic segments in cases with maternal uniparental disomy 14 suggests more than one imprinted region
Authors: Kotzot D
Published: March 2003

The results of molecular investigations of 21 cases with complete or segmental maternal uniparental disomy (UPD) 14 published in the literature were compared with respect to isodisomic and heterodisomic segments. The aim of the study was to find hints toward imprinted regions other than the recently defined imprinted segment 14q32. Three regions with no isodisomic molecular marker were found. The most distal of these regions located on 14q32.12 and 14q32.13 supports the hypothesis of genomic imprinting as the cause of the maternal UPD 14 phenotype by synteny to the maternally imprinted region on mouse distal chromosome 12 and correlation with the recently defined imprinting cluster on human chromosome 14q32. The other two heterodisomic areas located on 14q11.2→14q12 and 14q21.1→14q31.2 are hints toward one or more additional regions of genomic imprinting on human chromosome 14.
The LPL S447X cSNP is associated with decreased blood pressure and plasma triglycerides, and reduced risk of coronary artery disease
Authors: Clee SM , Loubser O , Collins J , Kastelein JJP , Hayden MR
Published: March 2003

Linkage of the lipoprotein lipase (LPL) gene to blood pressure levels has been reported. The LPL S447X single nucleotide polymorphism (cSNP) has been associated with decreased triglycerides (TG), increased high density lipoprotein cholesterol, and a decreased risk of coronary artery disease (CAD), which may occur independently of its beneficial lipid changes. To investigate the relationship between LPL S447X cSNP and these parameters, we studied a cohort of individuals with familial hypercholesterolemia in whom blood pressures and information regarding the use of blood pressure lowering medications were available. Carriers of the S447X variant had decreased TG (1.21±0.47 vs. 1.52±0.67, p<0.001) and a trend towards decreased vascular disease (12.7 vs. 19.5%) compared to non‐carriers. More interestingly, however, carriers of this cSNP had decreased diastolic blood pressure compared to non‐carriers (78±10 vs. 82±11, p=0.002), evident in both men and women, youths and adults, with similar trends for systolic blood pressure. Furthermore, the decrease in blood pressure appeared independent of the decrease in TG (p=0.02), suggesting that the LPL protein may have a direct influence on the vascular wall. This suggests an additional mechanism whereby this variant may have protective effects, independent of changes in plasma lipid levels.
Apolipoproteins AI, B, and E polymorphisms in severe aortic valve stenosis
Authors: Avakian SD , Annicchino‐Bizzacchi JM , Grinberg M , Ramires JAF , Mansur AP
Published: March 2003

Hypercholesterolemia has been related to aortic valve stenosis (AS). Polymorphisms of apolipoproteins (apo) AI, B, and E are associated with variable levels of plasma lipids, but the association between these polymorphisms and AS is unknown. In a case–control study of groups matched by age, sex, comparable body mass index, hypertension, triglycerides, high‐density lipoprotein (HDL) cholesterol, and low‐density lipoprotein (LDL) cholesterol, we analyzed the distribution of apo AI A/G mutation, apo B signal peptide insertion/deletion, apo B XbaI restriction fragment length, and apo E polymorphisms in 62 non‐diabetic patients with severe aortic valve stenosis and 62 control subjects. All patients underwent echocardiographic analysis. Univariate analysis showed a higher prevalence of the XbaI X+/X+ genotype (p=0.007) of apo B and the apo E2 allele (p=0.034) in patients with severe AS. Apo polymorphisms were not associated with lipid levels, left ventricular mass, or the aortic gradient.
The fragile X gene and its function
Authors: Oostra BA , Chiurazzi P
Published: March 2003

The fragile X syndrome represents the most common inherited cause of mental retardation worldwide. It is caused by a stretch of CGG repeats within the fragile X gene, which increases in length as it is transmitted from generation to generation. Once the repeat exceeds a threshold length, no protein is produced resulting in the fragile X phenotype. Ten years after the discovery of the gene, much has been learned about the function of the fragile X protein. Knowledge has been collected about the mutation mechanism, although still not all players that allow the destabilization of the CGG repeat are known.
Klinefelter syndrome is a common cause for mental retardation of unknown etiology among prepubertal males
Authors: Khalifa MM , Struthers JL
Published: March 2003

Klinefelter syndrome (KS) has not typically been associated with mental retardation (MR), however, in recent years a growing body of evidence suggested that KS boys often experience language deficits and academic difficulties. In this study, we screened DNA samples from 1205 patients originally referred for fragile X syndrome (FRAX) testing, because of MR of unknown etiology and detected 8 KS patients. A similar number of males in the same age group were found to have FRAX; 3 of them had a family history of FRAX. Based on these findings, KS might be the most common cause of MR of unknown etiology among prepubertal males. Because of the significant benefits of early recognition and treatment of KS, we emphasize the importance of cytogenetic testing of all prepubertal males with cognitive impairment even without dysmorphic features.
Epigenetic contributors to the discordance of monozygotic twins
Authors: Singh SM , Murphy B , O'Reilly R
Published: March 2003

Human monozygotic (MZ) twins estimated to occur once in 250 live births, result from an errant decision by embryonic cell(s) to develop as separate embryos. They are considered genetically identical and any phenotypic discordance between them has been used to implicate the role of environment. More recent literature, however, has questioned these assumptions but the frequency and the nature of any genetic discordance between MZ twins remains poorly understood. We will review published cases of phenotypic and genetic discordance between monozygotic twins to argue that not all discordance between such twins is due to differences in environment. The causes of reduced concordance between MZ twins remains poorly understood. They represent among the challenging aspects of the genetics of complex multi‐factorial traits and diseases. A number of questions regarding the published results on MZ twins merit a re‐assessment in the light of modern molecular insight of the human genome. Such an assessment is needed in directing future studies on MZ twins. In particular, we will deal with the origin, development, genetic and epigenetic factors that may have implications in discordance of the MZ twin pairs.
α1‐Antitrypsin null alleles: evidence for the recurrence of the L353fsX376 mutation and a novel G→A transition in position +1 of intron IC affecting normal mRNA splicing
Authors: Seixas S , Mendonça C , Costa F , Rocha J
Published: March 2003

α1‐Antitrypsin (PI) deficiency is a common autosomal recessive disorder associated with emphysema and liver disease, which may result from a wide spectrum of mutations causing a reduction of serum levels (deficient alleles) or a total lack of circulating protein (null alleles). We report two different alleles associated with the absence of isoelectric focusing banding patterns in Portuguese patients with emphysema. The first allele, Q0ourém, results from the recurrence of the defining mutation of the Q0mattawa variant (L353fsX376) on a M3 normal background. The second allele, Q0porto, has a novel G→A mutation at position +1 of the intron IC (IVS1C+1G→A), which restricts mononuclear phagocyte transcripts to mRNA species resulting from the direct splice of exon IA to exon II. The absence of this normal splice alternative in the liver, where PI is primarily synthesized, provides a basis for the pathogenic effects of this mutation.
Lack of association between methylenetetrahydrofolate reductase (MTHFR) C677T and ischaemic heart disease (IHD): family‐based association study in a Spanish population
Authors: González‐Pérez E , Via M , López‐Alomar A , Esteban E , Valveny N , Bao M , Domingo E , Moral P
Published: March 2003

The effect of the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene, traditionally associated with ischaemic heart disease (IHD), was assessed in a Spanish population. The transmission disequilibrium test (TDT) was used to determine a possible association in a sample of 101 trios of IHD patients. The distribution of MTHFR genotypes was similar in the IHD subjects and the parental group; the TT genotype was present in 14.9% of IHD patients, as compared to 15.2% in the parents. The frequency of the T allele was also similar in IHD cases and parents (39.6% vs. 42.4%; p = 0.649). The TDT confirmed that the observed transmission of the T allele did not deviate significantly from the expected one (χ2 = 0.743; p > 0.4). Our TDT analysis clearly demonstrates a lack of association between the T allele of the C677T mutation in MTHFR and cardiovascular artery disease, both for the general group and for different risk subgroups (smokers, hypertension, male sex, overweight and type A behaviour pattern) in the Spanish population.
Genetic and clinical analysis of spinocerebellar ataxia type 8 repeat expansion in Yugoslavia
Authors: Topisirovic I , Dragaševic N , Savic D , Ristic A , Keckarevic M , Keckarevic D , Culjkovic B , Petrovic I , Romac S , Kostic V S
Published: March 2003

Spinocerebellar ataxia type 8 (SCA8) is a slowly progressive ataxia causally associated with untranslated CTG repeat expansion on chromosome 13q21. However, the role of the CTG repeat in SCA8 pathology is not yet well understood. Therefore, we studied the length of the SCA8 CTA/CTG expansions (combined repeats, CRs) in 115 patients with ataxia, 64 unrelated individuals with non‐triplet neuromuscular diseases, 70 unrelated patients with schizophrenia, and 125 healthy controls. Only one patient with apparently sporadic ataxia was identified with an expansion of 100 CRs. He had inherited the expansion from his asymptomatic father (140 CRs) and transmitted the mutation to his son (92 CRs). Paternal transmission in this family produced contractions of 40 and 8 CRs, respectively. None of the subjects from other studied groups had an expansion at the SCA8 locus. In the control group the number of CRs at the SCA8 locus ranged from 14 to 34. Our findings support the notion that allelic variants of the expansion mutation at the SCA8 locus can predispose to ataxia.
Sleep disturbance in mucopolysaccharidosis type III (Sanfilippo syndrome): a survey of managing clinicians
Authors: Fraser J , Wraith JE , Delatycki MB
Published: March 2003

Sanfilippo syndrome (mucopolysaccharidosis type III) is the commonest mucoploysaccharidosis. It causes neurodegeneration with often profound sleep and behavioral disturbance. Management of the sleep disturbance is difficult and inconsistent. In this study, we surveyed clinicians with particular expertise in the management of individuals with mucopolysaccharidoses. We found that sleep problems are almost universal in this patient population and that no one treatment is consistently viewed as beneficial. Among the clinicians surveyed, melatonin is reported as the medication most likely to be of benefit. Benzodiazepines, chloral hydrate, antihistamines and antipsychotic agents are overall reported as less efficacious. The major side‐effect of the medications as a group was reported to be daytime somnolence. Based on this study, recommendations are given regarding the approach to sleep disturbance in Sanfilippo syndrome.
Partial splenic embolization for hypersplenism before and after liver transplantation
Authors: Sockrider Christopher S , Boykin Kevin N , Green John , Marsala Andrew , Mladenka Mary , McMillan Robert , Zibari Gazi B
Published: March 2003

Abstract: Partial splenic embolization (PSE) has been demonstrated to be an effective alternative to splenectomy for patients with hypersplenism. Splenectomy in these patients can be associated with an increased risk of perioperative complications, overwhelming post‐splenectomy sepsis (OPSS) and mortality. Partial splenic embolization has the advantages of non‐ operative intervention and resolution of the complications of hypersplenism. We report the use of this technique in patients with portal hypertension and hypersplenism awaiting liver transplant and patients that have undergone othotopic liver transplantation (OLTx) with persistent hypersplenism post‐transplant. Six patients − three awaiting liver transplantation and three patients with persistent hypersplenism status post‐OLTx − were treated during the period of 1993–99 at the LSUHSC/Willis Knighton Regional Transplant Center in Shreveport, Louisiana. Three patients were male and three female. All six patients had concomitant thrombocytopenia and neutropenia with platelet counts below 50 000. Patients underwent selective arterial catheterization and embolization via a percutaneous approach with Cook microcoils or PVA particles. The lower pole of the spleen was selectively embolized in all patients to achieve a 30−50% reduction in flow as determined by angiography. Patients were followed with routine computed tomography (CT) scans, platelet and WBC counts for a mean of 26 months in the pre‐transplant and 37 months in the post‐transplant group. In both groups, all patients had persistent resolution of thrombocytopenia and neutropenia after embolization. In the post‐transplant group, one patient had persistent splenomegaly and required splenectomy for pain control. No procedure‐related complications occurred in any patient. In this limited review, PSE appears to be a safe and effective treatment of persistent hypersplenism in patients with portal hypertension and those who have undergone OLTx.
Increased early morbidity and mortality with acceptable long‐term function in severely obese patients undergoing liver transplantation
Authors: Sawyer Robert G , Pelletier Shawn J , Pruett Timothy L
Published: March 2003

The effect of obesity on outcomes following liver transplantation remains unclear. We reviewed our experience with 302 liver transplants in 277 patients from September 1989 to September 1996 to determine the effect of body mass on outcome. Two hundred and seventeen transplants were performed in patients with a body mass index (BMI)<30 kg/m2, 55 in patients with a BMI of 30–34 kg/m2 (obese), and 30 in patients with a BMI>35 kg/m2 (severely obese). Non‐weight related pre‐operative demographics were similar between groups with the exception of an increased frequency of cryptogenic cirrhosis among the obese and severely obese patients. Intra‐operative transfusion requirements were greater for the severely obese group (16.2±3.5 units versus 9.1±0.8 units for the non‐obese, p=0.0004), though not when normalized to body weight (0.14±0.03 units/kg versus 0.13±0.01 units/kg, p>0.05). Post‐operatively, severely obese patients had a higher rate of wound infection (20 versus 4%, p=0.0001) and death attributed to multisystem organ failure (15 versus 2%, p=0.0001), although overall mortality prior to discharge and total complications were not different between groups. Actual 1‐yr graft survival showed a negative trend in the severely obese group (67 versus 81% for non‐obese, p=0.07), but both 3‐yr graft survival and patient survival were similar to non‐obese patients (p=0.12 and 0.17, respectively by the Cox–Mantel test). Liver transplantation in severely obese patients is associated with wound infection and early death from multisystem organ failure, but has similar long‐term outcomes when compared to non‐obese controls.
Immunoreactive trypsinogen levels in pediatric patients with intestinal failure awaiting intestinal transplantation
Authors: Rovera Giuseppe M , Sigurdsson Luther , Reyes Jorge , Bouch Lisa D , Naylor Edwin W , Kocoshis Samuel A
Published: March 2003

The aim of this study was to evaluate pancreatic function in total parenteral nutrition (TPN)‐dependent children with permanent intestinal failure by measuring immunoreactive trypsinogen (IRT) levels. Between 1992 and 1996, 105 pediatric patients with permanent intestinal failure were referred to the Children's Hospital of Pittsburgh for small intestinal transplant evaluation. Serum samples were available from 55 of them. Ten suffered from intestinal pseudo‐obstruction or microvillus inclusion disease, while 45 had short bowel syndrome (SBS). IRT levels were significantly higher (p<0.001) in SBS patients (89.4±9.2 ng/mL) compared to controls (43.4±5.6 ng/mL) without liver, gastrointestinal, or kidney disease. IRT levels did not correlate with liver injury, length of bowel, or the cause of SBS. Five of 20 patients who underwent intestinal transplantation developed pancreatitis during a median post‐operative follow up 15.4 months later. IRT levels failed to predict who would develop pancreatitis post‐transplant. The data suggest that elevated plasma IRT levels are common among children with intestinal failure, but fail to identify patients at risk for pancreatitis post‐transplant.
Prophylactic photopheresis and chronic rejection: effects on graft intimal hyperplasia in cardiac transplantation
Authors: Barr Mark L , Baker Craig J , Schenkel Felicia A , McLaughlin Susan N , Stouch Bruce C , Starnes Vaughn A , Rose Eric A
Published: March 2003

Background: Despite the decreased incidence of acute rejection episodes and improvements in short and intermediate term graft survival with current immunosuppressive agents, there has been little progress in decreasing the morbidity and mortality from chronic rejection. This phenomenon may, in part, be related to the development of a humoral immune response with increases in anti‐HLA antibodies, which presents as accelerated graft arteriopathy with intimal hyperplasia.  Methods: Based on prior experimental work, a pilot, prospective, randomized study was performed in 23 primary cardiac transplant recipients to determine whether the addition of prophylactic photopheresis to a cyclosporine, azathioprine and prednisone regimen was safe and resulted in decreased levels of panel reactive antibodies (PRA) and transplant arteriopathy.  Results: There was no difference between the two groups in regard to infection or acute rejection incidence. The photopheresis group had a significant reduction in PRA levels at two time points within the first 6 postoperative months. Coronary artery intimal thickness was significantly reduced in the photopheresis group at 1‐yr (0.23 vs. 0.49 mm, p<0.04) and 2‐yr (0.28 vs. 0.46 mm, p<0.02) follow‐up compared with the control group.  Conclusion: In this small pilot study, photopheresis is a safe, well‐tolerated immunomodulatory technique that is capable of decreasing the severity of chronic rejection manifesting as post‐transplant graft intimal hyperplasia.
Piggyback technique and selective use of veno‐venous bypass in adult orthotopic liver transplantation
Authors: Reddy K Sudhakar , Johnston Thomas D , Putnam Lee Ann , Isley Michael , Ranjan Dinesh
Published: March 2003

Background. The piggyback technique (PT), with preservation of the cava, is being used more frequently in adult orthotopic liver transplantation (OLT). The advantages of PT include hemodynamic stability during the anhepatic phase without a large‐volume fluid infusion and obviating the need for veno‐venous bypass (VVB). At our center, we changed our practice in July 1997 from the standard technique (ST) of OLT with routine use of VVB to PT and selective use of VVB. The purpose of the present study was to analyze the results with the two different practices, ST‐routine VVB versus PT‐selective VVB.  Methods. Forty OLTs were performed during the period July 1995–July 1997 using ST‐routine VVB (group I) and 36 during August 1997–December 1998 using PT‐selective VVB (group II). The etiology of liver disease was similar in the two groups, with hepatitis C and alcoholic liver disease accounting for half of the patients in each group. The UNOS status, age, sex, and percentage of patients with previous upper abdominal surgery were also similar between the two groups.  Results. In the PT‐selective VVB era (group II), 34/36 patients (94%) underwent OLT with PT and VVB was used for 8 (22%) patients. The decision to use VVB was elective for 3 patients (fulminant hepatic failure, 2; severe portal hypertension, 1) and urgent for 5 patients (hemodynamic instability during hepatectomy). The intraoperative use of packed red blood cells (PRBC) (mean±SD) was 15±12 units for group I and 9±8 units for group II (p=0.023). Anastomosis time and total operating time (mean±SD) were 91±30 min and 9.5±3.2 h, respectively, for group I patients compared with 52±28 min and 7.6±1.6 h, respectively, for group II patients (p<0.0001 and 0.002, respectively). Median post‐operative stays in the intensive care unit (ICU) and in the hospital were 5 and 17 d, respectively, for group I and 4 and 11 d, respectively, for group II (p=NS). Mean serum creatinine on day 3 was similar in the two groups. Median hospital charges for group I patients were $105 439 compared with $91 779 for group II patients (p=NS). The 1‐year actuarial graft and patient survival rates were 78% and 82%, respectively, for group I, and 92% and 95%, respectively, for group II.  Conclusions. PT is safe and can be performed in the majority of adult patients (>90%) undergoing OLT. With the routine application of the piggyback procedure, the use of VVB has been reduced to 20% of OLTs at our center. The practice of piggyback technique with the selective use of VVB is associated with shorter anhepatic phase and total operating time, lower blood product use, a trend towards shorter hospital length of stay, and reduced hospital charges compared with standard technique of OLT with routine use of VVB.
Thoracic organ donor characteristics associated with successful lung procurement
Authors: McElhinney Doff B , Khan Junaid H , Babcock Wayne D , Hall Timothy S
Published: March 2003

Purpose: A shortage of suitable donors is the major impediment to clinical lung transplantation. The rate of lung recovery from potential donors is lower than that for other organs. The purpose of this study was to evaluate what factors could be modified to improve the rate of cadaver lung recovery.  Methods: We performed a retrospective review of records from all thoracic organ donors procured by the California Transplant Donor Network between 1 January 1995 and 31 May 1997 (251 donors) to determine which donor management factors were associated with an increased likelihood of successful lung procurement.  Results: There were 88 lung donors (L) and 163 donors from which hearts but no lungs were procured (H). Longer time to donor network referral was associated with a reduced chance for successful lung procurement. Donor age, cause of death, and time of admission were not important factors. Most donors in this study had an acceptable A‐a gradient at admission to the hospital but lung function deteriorated in group H. Corticosteroid usage and initially clear breath sounds were independent predictors of successful procurement by multivariate analysis.  Conclusions: Early contact with the donor referral network, and corticosteroids may help to improve the lung procurement rate from potential donors.
Kidney and pancreas transplantation without a crossmatch in select circumstances – it can be done
Authors: Matas Arthur J , Humar Abhinav , Kandaswamy Raja , Payne William D , Gruessner Rainer W G , Sutherland David E R
Published: March 2003

Given the constant flux in caseload and the number of personnel available in the OR, waiting for a final XM often prolongs organ preservation time (a room available at the time a XM is started is not available when the XM is completed). Longer preservation is associated with increased DGF and decreased graft survival. We have shown in a retrospective analysis that final XMs on 0% PRA recipients were always negatitve (Transplantation, 1999). We now describe a policy of: a) not doing screening XM and b) proceeding to the OR without a XM, in situations where the recipients's PRA has been documented to be 0% and when there have not been any interim transfusions (and the OR is ready before XM completion). Final XM is completed after the transplant. All patients send sera every 6 weeks for PRA (antiglobulin technique). If ≥3 consecutive PRAs are 0%, no donar‐specific screening XM is done prior to calling the patient in for tx (UNOS allocation algorithm used). If there have not been any interim transfusions, we have proceeded to tx prior to completion of the final XM.  Between 1/1/98‐12/31/99, we did 109 CAD kidney (K) and 79 simultaneous kidney pancreas (SPK) tx; 67 (61%) K and 56 (71%) SPK had 0% PRA. Of the 0% PRA, 25/67 (37%) K and 28/56 (50%) SPK had no pretx XM. For K with no XM, cold ischemia was shorter (13.2±0.2 vs. 18±0.9 hrs, p=0.01) and DGF less (12% vs. 24%, p=0.3); for SPK with no XM, cold ischemia was shorter (15.2±2 vs. 18±0.9 hrs, p=0.1); no diff in DGF. All post‐XM were negative and there were no hyperacute rejections; there was no diff in acute rejection episodes. Actuarial 1 yr graft survival: no XM‐K=87.5%, SKP=82%; Yes XM‐K=88%, SKP=86% (NS). Our data suggests it is safe, in select circumstances, to proceed to the OR without a XM. Elimination of the screening XM for 0% PRA candidates saves money. Proceeding of the OR (if available) without a final XM shortens cold ischemia time.
Polyoma viral infection in renal transplantation: the role of immunosuppressive therapy
Authors: Barri Yousri M , Ahmad Ibrahim , Ketel Beverley L , Barone Gary W , Walker Patrick D , Bonsib Stephen M , Abul‐Ezz Sameh R
Published: March 2003

Background: Polyoma virus infection in renal transplant recipients has been observed with increasing frequency in recent years. Renal allograft involvement in this condition may occur as a result of primary infection or secondary to reactivation of the latent virus. Interstitial nephritis, ureteric stenosis, rise in serum creatinine and allograft function loss have been attributed to this viral infection.  Methods: In this study we reviewed our experience with 8 patients who developed polyoma viral infection confirmed by allograft biopsy. All patients were receiving mycophenolate mofetil as part of the immunosuppression and 7 of the 8 patients were on tacrolimus. All patients have biopsy proven polyoma viral infection. The following therapeutic maneuvers were carried out following the diagnosis of polyoma viral infection: 1) stopping mycophenolate and 2) switching tacrolimus to cyclosporine or reducing the tacrolimus dose to adjust it at a lower therapeutic trough level. The clinical course and outcome of our patients were reviewed in relation to manipulation of immunosuppressive medications.  Results: The incidence of this infection in our transplant program in the last 3 yr was 5.3%. Seventy‐five percent of the patients had at least one rejection episode and 63% had more than one rejection episode. The main risk factor for the development of polyoma viral infection was related to the intensity of immunosuppression. The use of antirejection therapy after histological diagnosis of polyoma virus infection was not associated with improvement of renal function despite the histological appearance of acute rejection. Thus, the interstitial nephritis associated with polyoma viral infection appears to be an inflammatory response to the virus rather than acute rejection. Six out of the 8 patients stabilized renal function with reduction in immunosuppression.  Conclusions: Reduction in immunosuppression was associated with the stabilization of renal function when instituted early. However, these patients were left with a degree of allograft dysfunction and their outcome may be significantly compromised. The lack of effective antiviral therapy for polyoma virus may limit the use of newer and more potent immunosuppressive medications.
Ganciclovir pharmacokinetics and cytokine dynamics in renal transplant recipients with cytomegalovirus infection
Authors: Tornatore Kathleen M , Garey Kevin W , Saigal Navid , Reed Kris , Murray Brian , Ingalls Elizabeth , DiFrancesco Robin , Forrest Alan , Morse Gene , Venuto Rocco
Published: March 2003

Ganciclovir is considered to be the first‐line treatment for cytomegalovirus (CMV) in renal transplant recipients. This infection is also associated with elevations of specific plasma cytokines post‐transplantation. To investigate daily cytokine response to therapy and ganciclovir pharmacokinetics, 4 transplant recipients (3 males, 1 female) with stable renal allograft function diagnosed with CMV infection were enrolled less than 4 months post‐transplant. A creatinine clearance (ClCr) was generated by the Cockroft–Gault (C‐G) equation (range: 42.3–68.5 mL/min) to determine ganciclovir dosing. Blood samples were collected for ganciclovir and cytokine [including interleukin (IL)‐1β, IL‐2, IL‐3, IL‐4, IL‐6, IL‐8, IL‐10, TNF‐α, GM‐CSF, and interferon (IFN)‐γ analyses after 7 d of intravenous (i.v.) ganciclovir (dosage range: 165–400 mg daily) therapy and again after 7 d of oral (p.o.) ganciclovir (dosage range: 1000 mg, 2–3 times daily) therapy.  Pharmacokinetic ganciclovir was described with a two‐compartment model. Total clearance of ganciclovir was consistently greater than ClCr, suggesting tubular secretion. Peak concentrations for i.v. ganciclovir averaged 8.39±1.87 μg/mL with minimum concentrations of 0.48±0.35 μg/mL. Plasma concentrations were lower but more sustained during a p.o. dosing interval (max=2.12±0.58 μg/mL, min=1.15±0.34 μg/mL). IL‐6, IL‐8, IL‐10, and TNF‐α were detectable at multiple times during the study periods while the remainder of the cytokines were only intermittently detectable. Average concentrations (i.v. versus p.o. study period) for TNF‐α were 40.1±17.5 versus 22.1±11.2 pg/mL, for IL‐8 were 17.1±15.6 versus 4.12±2.59 pg/mL, and for IL‐10 were 7.39±5.54 versus 2.64±1.06 pg/mL. Concentrations were similar for IL‐6 during both studies (9.39±5.42 versus 14.7±14.8 pg/mL). TNF‐α, IL‐8, and IFN‐γ appeared to correlate with CMV antigenemia. Further investigation of ganciclovir disposition and changes in plasma cytokines in renal transplant recipients during CMV infection may provide insight into variable antiviral responses in renal transplant recipients.
Organ donation in Hawaii: impact of the final rule
Authors: Higashigawa Kevin H , Carroll Chris , Wong Linda L , Wong Livingston M
Published: March 2003

Background. In an effort to increase organ donation, the Department of Health and Human Services issued the Final Rule in 1998. The Health Care Financing Administration (HCFA) later required hospitals to notify organ procurement organizations (OPO) of all deaths and imminent deaths in order to remain eligible for Medicare and Medicaid reimbursement. We set out to determine the impact of the Final Rule on organ donation in Hawaii.

Methods. Medical records of all deaths between January 1999 and December 2000 at 17 acute‐care hospitals were reviewed to determine the number of medically suitable, potential organ donors.

Results. Of 9427 deaths, 144 were potential organ donors. In 1999, before the Final Rule, 60 of 75 (80%) potential donors were identified and 40 (53%) were referred to the OPO. In 2000, after the Final Rule, the identification rate was 83% and the referral rate was 70%.

Conclusions. Although, the Final Rule increased the referral rate slightly, medical centres must continue to improve their identification of potential donors and prompt referral. This is not only to comply with the Final Rule, but ultimately to increase organ donation to meet the needs of the ever‐expanding list of patients waiting for organs.
Living related liver transplantation for recurrent hepatocellular carcinoma in a normal liver
Authors: Hess Donavon , Humar Abhinav , Sielaff Timothy D
Published: March 2003

The role of liver transplantation for hepatocellular carcinoma (HCC) is evolving. In patients with advanced liver disease and early stage HCC, transplantation offers the best hope for cure. A living donor offers the optimal approach to a timely transplant, before disease progression obviates the potential benefit. But extending the indications beyond those designated by the United Network for Organ Sharing (UNOS) for liver transplantation for HCC is controversial [Hepatology 2001: 33: 1073; Liver Transplant 2000: 6: S1]. Cadaver split techniques and use of living donors are potentially compelling ways to test the limitations of liver transplantation for HCC, without notably reducing the cadaver organ pool. Herein, we report a rare case of a patient who developed a well‐differentiated HCC in a normal liver. After resection of the index lesion and, later, of a remote recurrent lesion, a living donor liver transplant was offered. The natural history of this lesion and the management of transplantation in this setting are discussed.
Amantadine in depressive patients with Borna disease virus (BDV) infection: an open trial
Authors: Dietrich Detlef E , Bode Liv , Spannhuth Carsten W , Lau Timo , Huber Thomas J , Brodhun Bonita , Ludwig Hanns , Emrich Hinderk M
Published: March 2003

Objective:

Originally introduced into pharmacotherapy as an antiviral compound, amantadine was shown to also have multiple pharmacological effects on the central nervous system. In addition, only a few studies reported on certain antidepressive properties of amantadine. This effect was highlighted by the discovery of its antiviral effect on Borna disease virus (BDV), which is hypothesized to be an etiopathogenetic factor to subtypes of affective disorders. Therefore, the therapeutical use of amantadine in BDV‐infected depressive patients was investigated.   Methods: In this open trial, amantadine was added to antidepressive and/or mood‐stabilizing compounds treating BDV‐infected depressed patients (n=25) with bipolar or major depressive disorders. Amantadine was given twice a day (100–300 mg/day) for a mean of 11 weeks. Antidepressive treatment response was measured on the Hamilton rating scale for depression (HAM‐D) and/or with an operationalized diagnostic criteria system (OPCRIT; version 3.31). Virological response was measured by expression of BDV infection parameters in blood samples.   Results: The overall response rate of the amantadine augmentation in the BDV‐infected patients with regard to depressive symptoms was 68% after a mean of 2.9 weeks of treatment. Bipolar I patients improved faster and did not show any following hypomania. In addition, the decrease of depression tended to correspond with the decrease in viral activity.   Conclusion: Amantadine appears to show a remarkable antidepressive efficacy in BDV‐infected depressive patients. The antidepressive effect in this open trial appeared to be comparable to standard antidepressives, possibly being a result of its antiviral effect against BDV as a potentially relevant etiopathogenetic factor in these disorders.
Serum lithium levels and the outcome of maintenance therapy of bipolar disorder
Authors: Hopkins Heather S , Gelenberg Alan J
Published: March 2003

A literature review was conducted to locate studies that compared different serum lithium levels in the long‐term treatment of patients with bipolar disorder and articles about factors that may affect serum lithium levels. Patients with bipolar disorder on long‐term treatment with lithium are typically maintained at serum lithium concentrations between 0.6 and 1.0 mEq/L. Although there are individual exceptions, serum lithium levels below 0.6 mEq/L have been shown in controlled clinical trials to be less effective in preventing relapses than levels within this range, whereas levels much above 1.2 mEq/L can lead to toxicity. Differences in efficacy between levels within the accepted range have not been established. However, higher levels are associated with greater side effects, which can lead to poor compliance. Interindividual variation in pharmacokinetics and pharmacodynamics, as well as such external factors as diet and concomitant medications, can affect serum lithium levels.
Li+/Mg2+ competition at therapeutic intracellular Li+ levels in human neuroblastoma SH‐SY5Y cells
Authors: Layden Brian , Diven Conrad , Minadeo Nicole , Bryant Fred B , Mota de Freitas Duarte
Published: March 2003

Objectives:

One proposed mechanism of lithium action in the treatment of bipolar disorder is that Li+ competes with Mg2+ for Mg2+ binding sites within the cell. In this study, we investigated this competition at therapeutic intracellular Li+ levels in human neuroblastoma SH‐SY5Y cells.   Methods: We used fluorescence spectroscopy and a Mg2+ indicator, furaptra, to investigate this competition in human neuroblastoma SH‐SY5Y cells. Atomic absorption spectrophotometry was used for determination of the intracellular Li+ levels.   Results: The neuroblastoma cells, incubated in 15 mM or 30 mM Li+‐containing buffer, showed a significant increase in free intracellular Mg2+ levels [using a positive linear within‐groups contrast t‐test, the 15 mM condition produced t(2)=5.0, one‐tailed p<0.02, and the 30 mM Li+‐incubation conditions gave t(2)=9.2, one‐tailed p<0.006] but did not significantly increase over time in the Li+‐free condition [t(2)=0.1, one‐tailed p>0.96]. At the earlier times during the incubation (1 or 10 min for the 15 mM or 30 mM Li+‐containing buffers), the intracellular Li+ concentrations were 0.6–2.5 mM, values which are comparable to those reached in the brain of Li+‐treated patients.   Conclusion: We demonstrated that competition between Li+ and Mg2+ can occur at therapeutic intracellular Li+ levels.
The treatment of bipolar depression
Authors: Sachs Gary S , Koslow Courtney L , Ghaemi S Nassir
Published: March 2003

Objectives:

The treatment of the depressed phase of bipolar disorder is understudied and remains a common clinical dilemma for clinicians. Compared to the manic phases, episodes of bipolar depression are more frequent and of longer duration, yet the literature on this problem is minimal. The few methodologically sound studies find that treatment effective for unipolar depression are also efficacious for bipolar depression. However, standard antidepressant agents may cause acute mania or a long‐term worsening of bipolar illness. This paper reviews the available literature on the treatment of bipolar depression and offers recommendations for clinical management.

  Methods: A literature search was conducted using keywords ‘bipolar disorder’, ‘depression’, ‘drug therapy’, ‘antidepressants’, ‘lithium’, and ‘anticonvulsants’.

  Results: If effectively treated by lithium, patients are spared the risk of antidepressant‐induced mania. If lithium is not sufficient treatment for acute depression, the combination of lithium and a standard antidepressant appears to reduce the risk of affective switch, as well as the induction of a long‐term rapid‐cycling course. Additionally, tapering antidepressant medication after periods of sustained remission can be beneficial in limiting the risk of affective switch and acceleration of the cycle rate.

  Conclusions: Doctors must be cautious in prescribing antidepressants for bipolar depression. Use of antidepressants alone should be avoided.
A pilot study of rapid lithium administration in the treatment of acute mania
Authors: Keck Jr Paul E , Strakowski Stephen M , Hawkins John M , Dunayevich Eduardo , Tugrul Karen C , Bennett Jerry A , McElroy Susan L
Published: March 2003

Objectives:
The use of rapid lithium dosage administration, a strategy that could lead to rapid improvement in mania, has been largely unexamined. In this open‐label, pilot, acute‐treatment study, we sought to determine the safety and tolerability of lithium administered at 20 mg/kg/day. A secondary aim was to provide preliminary data regarding the efficacy of this strategy in ameliorating manic, depressive, and psychotic symptoms.   Methods: Fifteen patients hospitalized with DSM‐IV bipolar disorder, manic or mixed, and who provided written informed consent, received lithium 20 mg/kg/day for up to 10 days. Patients were evaluated for adverse effects daily. Lithium levels were obtained on days 2, 3, 4, 5, 7, and 10 or at study termination. Electrocardiograms (EKGs) were performed at baseline and on days 1–5, 7, and 10 or at study termination. Symptomatic improvement was assessed daily using the Young Mania Rating Scale, 24‐item Hamilton Depression Rating Scale, and the Scale for Assessment of Positive Symptoms (SAPS).   Results: Five of the 15 patients completed the 10‐day study period. Two patients dropped out due to adverse events. Seven patients did not complete the inpatient trial because of improvement sufficient to allow hospital discharge. All patients achieved serum lithium concentrations ≥0.6 mEq/L after 1 day of treatment; the mean±SD concentration on day 5 was 1.1 (±0.1) mEq/L on day 5. There were significant reductions from baseline to endpoint on all rating scales, except the SAPS bizarre behavior subscale.   Conclusions: These pilot data suggest that lithium 20 mg/kg/day was well tolerated and that this strategy may produce rapid improvement in affective and psychotic symptoms. These impressions require confirmation in double‐blind, randomized trials.