bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of a dup(5)(p15.3) by multicolor banding
Authors: Riordan D , Vust A , Wickstrom DE , Brown J , Chudley AE , Tomkins D , Chudoba I , Dawson AJ
Published: March 2003

A 7‐year‐old female was referred to the Genetics Clinic because of developmental delay and attentional difficulty. The patient was adopted and there was a nonspecific prenatal history of drug and alcohol abuse. The patient had clinical signs that were not compatible with typical fetal alcohol syndrome (FAS), although there was a history of alcohol exposure in utero, neurodevelopmental difficulties with learning and behavioral problems, and mild dysmorphisms. Cytogenetic analysis revealed an unbalanced female karyotype with a dup(5) containing additional chromosome 5 material at band 5p15.3. The dup(5) showed normal copy number of the cri‐du‐chat region on 5p15.2 using locus‐specific probes D5S721 and D5S23. Multicolor banding of chromosome 5 (MetaSystems) using partial chromosome paint (pcp) probes showed a duplication of band 5p15.3. The karyotype of the patient was therefore interpreted as follows: 46,XX,add(5)mat.ish dup(5)(p15.3)(wcp5 +, D5S271 +, D5S23 +, C84C11/T3 + +, pcp5p15.3 + +). The patient's biological mother and maternal half‐brother were found to carry the identical chromosome duplication. The clinical phenotype of the biological mother is complicated by a difficult lifestyle but there were apparent learning and behavioral difficulties at school. The half‐brother is nondysmorphic and presents with learning problems and attention deficit disorder (ADD). His physical examination was normal. To the best of our knowledge, this is the first report of a limited duplication of 5p15.3. The clinical significance of the dup(5)(p15.3) is still uncertain but may be the basis for learning and attention difficulties.
Spinal muscular atrophy in black South Africans: concordance with the universal SMN1 genotype
Authors: Wilmshurst J M , Reynolds L , Van Toorn R , Leisegang F , Henderson H E
Published: March 2003

Only one study has reported on the genetic basis of spinal muscular atrophy (SMA) in South African subjects. This was conducted in the Johannesburg region and has suggested that black South Africans only (indigenous Africans) differ from the norm. We have explored this further by DNA studies in 30 unrelated and racially diverse patients who reside in the Western Cape, and who were assessed as SMA subjects according to the internationally accepted inclusion criteria for SMA. These subjects were seen at the neurology clinic at Red Cross Children's Hospital in Cape Town during the period 1980–2001. Four had the type 1 form of SMA, 16 had type 2 and 10 had type 3. All patients were found to be homozygous for the loss of either exon 7 or exons 7 and 8 of the SMN1 gene.

Six additional patients had anterior horn cell disease but were negative for the SMN1 gene deletion. All six had exclusion features listed in the international guidelines.

This study shows that all patients from the Western Cape, which included 12 black South Africans, are no different genetically or phenotypically from the internationally recognized form of typical SMA.
Three novel mutations of the PKD1 gene in Korean patients with autosomal dominant polycystic kidney disease
Authors: Eo H‐S , Lee JG , Ahn C , Cho JT , Hwang DY , Hwang YH , Lee EJ , Kim YS , Han JS , Kim S , Lee JS , Jeoung DI , Lee SE , Kim UK
Published: March 2003

Mutations at the PKD1 locus account for 85% of cases of the common genetic disorder called autosomal dominant polycystic kidney disease (ADPKD). Screening for mutations of the PKD1 gene is complicated by the genomic structure of the 5′‐duplicated region encoding 75% of the gene. To date, more than 90 mutations of the PKD1 gene have been reported in the European and American populations, and relatively little information is available concerning the pattern of mutations present in the Asian populations. We looked for mutations of the PKD1 gene in 51 unrelated Korean ADPKD patients, using polymerase chain reaction (PCR) with primer pairs located in the 3′ single‐copy region of the PKD1 gene and by single‐strand conformation polymorphism (SSCP) analysis. We found three novel mutations, a G to A substitution at nucleotide 11012 (G3601S), a C to A substitution at nucleotide 11312 (Q3701X), and a C to T substitution at nucleotide 12971 (P4254S), and a single polymorphism involving a G to C substitution at nucleotide 11470 (L3753L). These mutations were not found in control individuals, and no other mutations in the 3′ single‐copy region of the PKD1 gene of patients with these mutations were observed. In particular, P4254S segregated with the disease phenotype. The clinical data of affected individuals from this study, and of previously reported Korean PKD1 mutations, showed that patients with frameshift or nonsense mutations were more prone to develop end‐stage renal failure than those with missense mutations. Our findings indicate that many different PKD1 mutations are likely to be responsible for ADPKD in the Korean population, as in the Western population.
A second kindred linked to DFNA20 (17q25.3) reduces the genetic interval
Authors: DeWan AT , Parrado AR , Leal SM
Published: March 2003

A family ascertained in the United States displays significant evidence of linkage to 17q25.3 (maximum two‐point LOD score 6.32). The non‐syndromic autosomal‐dominant hearing‐loss loci DFNA20 and DFNA26 map to this region. The 3‐unit support interval and haplotype for this USA kindred falls within the interval for DFNA20 and DFNA26 and reduces the region to 6.05 cM, according to the deCode genetic map. The same gene is probably responsible for both DFNA20/DFNA26. In addition, the USH1G locus maps to this region and could be an allelic variant of the gene responsible for DFNA20/DFNA26. Clinical data is presented for this kindred, where hearing‐impaired family members present with sloping audiograms with mid‐ and high‐frequency hearing loss, which progresses to hearing loss that affects all frequencies. The mean age of onset of hearing impairment is 13.2 years of age (standard deviation: 4.6 years).
Fabry disease: a functional and anatomical study of cardiac manifestations in 20 hemizygous male patients
Authors: Senechal M , Germain DP
Published: March 2003

Fabry disease (FD, OMIM 301500) is an X‐linked disorder of glycosphingolipid metabolism resulting from the deficient activity of α‐galactosidase A, a lysosomal acid hydrolase, leading to progressive lysosomal accumulation of incompletely metabolized neutral glycosphingolipids. Cardiac involvement is frequent. The objective of this study was to characterize the cardiac abnormalities in male patients affected with classic Fabry disease and define the context in which the clinicians were able to make the diagnosis.

Clinical evaluation, laboratory tests, electrocardiography (ECG) and echocardiography were performed in 20 hemizygous men (mean age 39 years, range 12–65 years). The context of diagnosis was obtained by review of patients' charts.

Left ventricular hypertrophy (LVH) and/or concentric remodeling were found in 12 patients (60%). Structural changes in mitral and aortic valves were found in 25% and 10% of cases, respectively. The sensitivity of the ECG Romhilt–Estes score for LVH was high (80%). Short PR interval (40%), ST segment abnormalities and conduction delay were frequent on ECG. Left ventricular mass index, ECG scores for LVH and systolic pulmonary pressure correlated positively with age. There was no relation between classic vascular risk factors and coronary artery disease, transient ischemic attack (TIA) or stroke. Diagnosis of Fabry disease was frequently suggested by nephrologists, dermatologists or geneticists.

Echocardiograph and ECG abnormalities are frequently observed in patients with Fabry disease. Cardiologists should be aware of the diagnosis of Fabry disease in patients presenting with LVH, concentric remodeling, mitral and aortic valve thickening on echocardiography, short PR interval and conduction defects on ECG.
Intravenous mycophenolate mofetil: safety, tolerability, and pharmacokinetics
Authors: Pescovitz Md , Conti D , Dunn J , Gonwa T , Halloran P , Sollinger H , Tomlanovich S , Weinstein S , Inokuchi S , Kiberd B , Kittur D , Merion Rm , Norman D , Shoker A , Wilburn R , Nicholls Aj , Arterburn S , Dumont E
Published: March 2003

An intravenous (i.v.) formulation of mycophenolate mofetil (MMF; CellCept®, Roche Pharmaceuticals, Inc., Palo Alto, CA) that will enable its administration to patients unable to tolerate oral medication is available. Two separate studies, an open‐labeled pharmacokinetic (PK) study and a double‐blind safety study, were performed. Within 24 h after transplant, 153 (safety study) and 45 (PK study) first or second renal transplant recipients were started on i.v. MMF 1 g Q12h or placebo (used in the safety study only, 2:1 MMF:placebo), given over 2 h via a dedicated peripheral venous catheter. In the safety study, per os (p.o.) MMF (1g Q12h) or placebo was administered, starting within 72 h after transplant, whereas in the PK study, p.o. MMF was started on the evening of day 5. Sequential blood samples obtained on study days 5 (i.v. MMF) and 6 (p.o. MMF) before and up to 12 h after the AM dose were analyzed for mycophenolic acid (MPA) and MPA glucuronide (MPAG) concentrations by high‐performance liquid chromatography. The area under the concentration curve (AUC) was calculated using the linear trapezoidal rule. The MPA AUC0–12 was higher for i.v. MMF than p.o. MMF (40.8±11.4 μg·h/mL vs. 32.9±15, p<0.001). There were no other significant PK differences for plasma MPA or MPAG. In the safety study (n=98 i.v. MMF vs. n=55 placebo), 11 patients (11%, i.v. MMF) and 4 patients (7%, placebo) discontinued their use of the drug because of an adverse event (AE). Overall, AEs were similar between i.v. MMF and placebo. Injection site phlebitis (4%) and thrombosis (4%) were observed only with i.v. MMF. MMF i.v. 1 g twice daily (b.i.d.) should provide efficacy at least equivalent to p.o. MMF without increased toxicity, and it provides an acceptable alternative dose form in the immediate period after transplant.
Roux‐en‐y venting jejunostomy in pancreatic transplantation: a novel approach to monitor rejection and prevent anastomotic leak
Authors: Zibari Gazi B , Aultman Donnie F , Abreo Kenneth D , Lynn Melissa L , Gonzalez Enrique , McMillan Robert W , Dies David , Work Jack , McDonald John C
Published: March 2003

Introduction: Pancreatic transplantation (PTx) with portal venous delivery of insulin and enteric drainage of the exocrine secretion is more physiologic than bladder‐systemic (BS) drainage. With portal‐enteric (PE) PTx, the diagnosis of acute rejection (AR) requires a percutaneous biopsy. The roux‐en‐y (RNY) venting jejunostomy in patients with PEPTx offers a novel approach to monitor rejection and prevent anastomatic leaks.  Methods. From January 1996 to December 1998, we performed 17 simultaneous kidney/pancreas transplants (SKPTx). The initial 4 patients underwent BS drainage and the subsequent 13 patients underwent RNY venting jejunostomy with PE drainage. All patients were treated with quadruple therapy. There were 9 males, 14 patients were Caucasian with a mean age of 32 yr (range 30–54 yr), and a mean pre‐transplantation duration of diabetes of 25 yr. Six patients underwent endoscopic donor duodenal biopsy through the jejunostomy to rule out clinically suspected AR. Gastrograffin was inserted into the jejunostomy to examine the integrity of anastamosis when indicated. In 9 out of 13 patients, the venting jejunostomy was taken down 9–12 months post‐transplantation after allograft function was stable.  Results. Actual patient, kidney, and pancreas graft survival rates were 100, 100 and 94%, respectively, after a mean follow‐up of 16 months. Renal allografts functioned immediately in 89% of patients. The mean length of hospital stay was 19 d. Four (23%) patients (2 with BS drainage and 2 with PE drainage) suffered an AR episode in the first month, and 4 (23%) patients had five AR from 3–36 months post‐transplantation. Other complications were post‐operative bleeding in 3 patients, wound infection in 2 patients and a proximal duodenal stump leak in 1 patient. In patients with clinical rejection, endoscopy through the venting jejunostomy showed inflamed, friable doudenal mucosa and doudenal biopsy findings were compatible with AR.  Conclusion. These preliminary results suggest that RNY venting jejunostomy with PE drainage can be used safely to diagnose and monitor pancreas AR and to diagnose and prevent anastamotic leaks. This technique will be even more useful to visualize transplanted duodenal mucosa, collect pancreatic secretions (amylase) for analysis and perform endoscopic retrograde cholangiopancreatography if needed to obtain pancreatic biopsies.
Urinary F2‐isoprostanes formation in kidney transplantation
Authors: Cracowski Jean‐Luc , Souvignet Claude , Quirin Nicolas , Grosbois Xavier , Bayle François , Stanke‐Labesque Françoise , Vialtel Paul , Bessard Germain
Published: March 2003

Background: Oxygen free‐radical mediated lipid peroxidation has been implicated in many diseases such as chronic renal failure, hemodialysis and chronic kidney transplant rejection. However, insight into the role of free radical generation in kidney transplantation has been constrained by the limitations of current indexes of oxidant stress in vivo. Isoprostaglandin F2α type‐III (iPF2α‐III, formerly known as 8‐iso‐prostaglandin F2α) is emerging as a reliable marker of oxidant stress in vivo. The purpose of our study was to investigate iPF2α‐III formation as an index of lipid peroxidation in the 5 d following kidney transplantation.  Methods: Urinary iPF2α‐III measurements were performed by enzyme immunoassay from day 1 to 5 in 11 patients undergoing kidney transplantation. Results were compared with 11 healthy volunteers matched in sex, age and cigarette smoking.  Results: Urinary excretion of iPF2α‐III at day 1 did not significantly differ between control and transplant group (111±17 vs. 92±10 pM/mM creatinine, respectively, NS). Urinary iPF2α‐III levels did not differ between day 1 to 5, and were not correlated to cold ischaemia time.  Conclusion: Our study shows no evidence of enhanced lipid peroxidation in the first 5 d following kidney transplantation.
Effect of lovastatin, an HMG CoA reductase inhibitor, on acute renal allograft rejection
Authors: Sahu Km , Sharma Rk , Gupta A , Gulati S , Agarwal Dk , Kumar A , Bhandari M
Published: March 2003

3‐Hydroxy‐3‐methyl glutaryl coenzyme A (HMG CoA) reductase inhibitors are established anti‐lipidemic agents. They also exert immunomodulatory effects. Two recent reports suggest that pravastatin may be useful in decreasing the incidence and severity of acute rejections (ARs) in heart and kidney transplant recipients. We undertook this prospective, randomized, placebo‐controlled, double blind trial to investigate the effect of lovastatin on acute renal allograft rejection. Sixty‐five consecutive, one‐haplotype‐matched, living related first renal transplant recipients were randomized to receive either lovastatin 20 mg/d or placebo for 3 months, in addition to cyclosporine, azathioprine, and steroids. Lipid levels, AR episodes, and liver and muscle enzymes were followed for 3 months post‐transplant. At the end of the study period, lovastatin had successfully controlled lipid levels. However, there was no effect on AR episodes (15.15% in the treatment group vs. 18.75% in the placebo group).
Emphysematous pyelonephritis in a renal allograft: successful treatment with percutaneous drainage and nephrostomy
Authors: Cheng Yuan‐Tso , Wang Hua‐Pin , Hsieh Hwei‐Ho
Published: March 2003

Emphysematous pyelonephritis in renal transplant allograft occurs rarely. This is a case report on a 55‐year‐old man who had renal transplantation in 1983 and developed post‐transplant diabetes mellitus in 1984. This patient suffered from fever and right low abdominal pain and was subsequently diagnosed as emphysematous pyelonephritis by computerized tomography. He was successfully treated with percutaneous drainage, percutaneous nephrostomy and parenteral antibiotics. Although the management of emphysematous pyelonephritis has been a subject of controversy, we recommend consideration of renal preservation in patients with few risk factors, especially in those patients presenting with chronic renal insufficiency, solitary kidney and transplant allograft.
Compliance and late acute rejection after kidney transplantation: a psycho‐medical perspective
Authors: Baines Lyndsay S , Joseph John T , Jindal Rahul M
Published: March 2003

Introduction: We examined the relationship between late acute rejection (LAR) after cadaveric kidney transplantation and medical compliance utilizing a modified version of the Long‐term Medication Behaviour Self‐efficacy Scale (LTMBS‐scale), a validated patient self‐report questionnaire. The original LTMBS‐scale uses a five‐point scale, however, our pilot study showed that patients found it difficult to discriminate between the five options. We therefore modified this to a three‐point scale.

Patientsand methods: We carried out a retrospective analysis of all patients who received a kidney transplant in our unit in the cyclosporin (CyA) era. We divided rejections into early and late rejection based on the time interval after transplantation. Graft rejection was confirmed by biopsy; LAR was defined as acute rejection occurring after 90 d. We retrospectively administered the modified LTMBS‐scale to determine individual patient confidence and self‐efficacy in taking their medications in a variety of situations (home, work, leisure, psychological and physical). Individual patient confidence and self‐efficacy was analysed in relationship to compliance behaviour.

Results: Twenty‐four questionnaires were distributed, 22 (92%) were returned fully completed. The overall results suggested that our patients surveyed were not particularly confident (mean score 2.17 out of maximum possible 3) in taking their medications in a variety of contexts. They demonstrated significantly less confidence (mean score 1.0) when experiencing physical (brittle bones, feeling `ill') and psychological (`sadness') side‐effects of medication and emotional reactions to the experience of chronic illness.

Conclusion: Negative physical and psychological states were related to low self‐efficacy with the taking of immunosuppressive medication, non‐compliance and subsequent LAR in our cohort of patients.
Diarrhoea following renal transplantation
Authors: Altıparmak Mehmet Rıza , Trablus Sinan , Pamuk Ömer Nuri , Apaydın Süheyla , Sarıyar Muzaffer , Öztürk Recep , Ataman Rezzan , Serdengeçti Kamil , Erek Ekrem
Published: March 2003

In this study, we retrospectively evaluated all attacks of diarrhoea in our renal transplant recipients that came to our medical attention between 1985 and 2000. Also, the clinical features of patients with diarrhoea were compared with the features of recipients without diarrhoea. We diagnosed 41 attacks of diarrhoea in 39 (12.6%) of 308 renal transplant recipients during this time period. An aetiology was detected in 33 (80.5%) of all diarrhoeal episodes and in seven (17.1%) of those the specific agent was diagnosed with the help of stool microscopy. The most frequent causes of diarrhoeal attacks were infectious agents (41.5%) and drugs (34%). Six (14.6%) episodes of diarrhoea were chronic and six were nosocomial. About two‐thirds of diarrhoea developed within the late post‐transplant period (>6 months). When recipients with diarrhoea were compared with those without diarrhoea, it was seen that diarrhoeal patients had significantly higher creatinine and significantly lower albumin levels when compared with the latter group (p < 0.05). Also, the frequency of antibiotic usage was significantly higher in diarrhoeal patients than in the control group (p < 0.05). Four (10.2%) patients with diarrhoea died despite institution of the appropriate therapy. Two of these deaths were primarily related to diarrhoea and the aetiological agent was Clostridium difficile in both these cases. During the 15‐yr study period, 3.6% of all deaths and 5.1% of infection‐related deaths in transplant recipients were secondary to diarrhoea. As a result, we observed that infections and drugs were the most frequent causes for diarrhoea in our series of renal transplant recipients. Also, diarrhoea was an important cause of mortality in this patient population.
Magnesium depletion in chronic terminal liver cirrhosis
Authors: Koivisto Mirja , Valta Päivi , Höckerstedt Krister , Lindgren Leena
Published: March 2003

Koivisto M, Valta P, Höckerstedt K, Lindgren L. Magnesium depletion in chronic terminal liver cirrhosis. Clin Transplant 2002: 16: 325–328. © Blackwell Munksgaard, 2002

Serum ionized magnesium represents less than 1% of the total body magnesium. The most reliable method to evaluate magnesium status is the magnesium loading test: In magnesium depletion its uptake is increased (20–50%) and is about 6% in normal magnesium status. There are no studies on magnesium status in chronic cirrhotics who may be in depletion. We performed magnesium loading test in 10 chronic cirrhotics listed for liver transplantation and in six healthy control patients. Magnesium sulphate 30 mmol was infused and urine magnesium was determined over 24 h. Serum ionized magnesium increased similarly in all patients. The uptake of magnesium was 8 ± 8% in control patients and 34 ± 26% in cirrhotics (p < 0.01). Chronic terminal cirrhotics are magnesium depleted which should be taken into account in case of liver transplantation and also in other interventions. Spot sampled serum ionized magnesium revealed magnesium depletion poorly.
Renal allograft loss due to proximal extension of ileofemoral deep venous thrombosis
Authors: Ramirez PJ , Gohh RY , Kestin A , Monaco AP , Morrissey PE
Published: March 2003

Renal allograft recipients with thrombophilic (hypercoagulable) states are at higher risk for early allograft loss. Presumably, the combination of endothelial injury at surgery and thrombophilia predisposes to arterial or venous thrombosis. Of 270 consecutive renal transplants at our center one allograft failed secondary to renovascular thrombosis. At exploration the iliac and renal veins were thrombosed. Thrombectomy and re‐implantation were attempted, but unsuccessful. Also noted at surgery was extensive clot in the femoral vein that could not be removed by embolectomy catheters. Post‐operatively, a Doppler ultrasound confirmed the presence of extensive deep venous thrombosis (DVT) in the femoral and popliteal veins. The adherent nature of this clot, the extent of clot found less than 12 h after renal transplantation and the absence of leg edema suggested that the DVT existed prior to surgery. This case demonstrates that a pre‐existing, asymptomatic DVT can precipitate allograft thrombosis and highlights the importance of diagnosing thrombophilia in patients undergoing renal transplantation. Current practices in our unit have evolved to include screening for thrombophilia in all patients with a suggestive history. As thrombophilic states are increasingly appreciated in the end‐stage renal disease population, effective management of these patients while on hemodialysis and at the time of renal transplantation presents an ongoing challenge.
Factors contributing to long graft survival in non‐heart‐beating cadaveric renal transplantation in Japan: a single‐center study at Kitasato University
Authors: Yoshida Kazunari , Endo Tadao , Saito Takeshi , Iwamura Masatsugu , Ikeda Masae , Kamata Koju , Sato Koshi , Baba Shiro
Published: March 2003

Yoshida K, Endo T, Saito T, Iwamura M, Ikeda M, Kamata K, Sato K, Baba S. Factors contributing to long graft survival in non‐heart‐beating cadaveric renal transplantation in Japan: a single‐center study at Kitasato University. Clin Transplant 2002: 16: 397–404. © Blackwell Munksgaard, 2002

A total of 107 cadaveric kidneys from non‐heart‐beating donors (NHBDs) have been transplanted between 1974 and 2000 at Kitasato University Hospital, Sagamihara, Japan. The patient survival of the 107 recipients of cadaveric renal transplants at 1, 5 and 10 yr was 0.857, 0.770 and 0.746, respectively. The 50% graft survival was 3.8 yr. The 5 and 10‐yr graft survival was 0.457 and 0.337, respectively. Twenty of the 107 recipients of non‐heart‐beating cadaveric renal transplantation had graft survival longer than 10 yr. Of these 20 patients, 14 survivors still maintain functioning renal grafts and two died with functioning graft, although the remaining four reverted to dialysis because of chronic rejection and nephropathy. The average graft survival of these 20 patients at the time of study was 13.3 yr and the longest was 21.4 yr. The average serum creatinine level at 10 yr after transplantation was 1.63 mg/dL, almost identical to that at 5 yr post‐transplant. The donors aged on average 40.2 yr; 13 were male and seven were female. The youngest donor was 9‐yr‐old and the oldest was 66. The graft survival was significantly better in the group with donor age younger than 55 yr (Log‐rank: p=0.007). The average weight of the renal graft was not different between the long and shorter graft survival groups. The average warm ischemic time and total ischemic time were 9.7 and 539.7 min, respectively. The duration of post‐transplant acute tubular necrosis averaged 9.2 days. These parameters tended to be shorter than those in recipients with graft survival >10 yr, but with no statistical significance. The mean numbers of acute rejection (AR) episode within 3 months after transplantation were 0.25 ± 0.66 and 0.92 ± 0.90 (p=0.020) in long survival and shorter survival groups, respectively. Long survivors had a significantly lower incidence of AR. Two of 20 cases received conventional immunosuppression with prednisolone, azathioprine and mizoribin, and 18 had prednisolone and calcineurin inhibitor (CNI). Kaplan–Meier analysis showed a significant contribution of CNI to graft survival (p=0.036). However, the graft survival reduction rate after 1 yr post‐transplant did not differ between conventional and CNI immunosuppression. These data suggest that renal grafts retrieved with proper organ procurement procedures from NHBDs may survive long‐term and help to overcome donor shortage.
Enteric drainage of a pancreas allograft is safe for patients with celiac sprue
Authors: Akoad Mohamed , Giraldo Mauricio , Monaco Anthony P , Hanto Douglas W , Uknis Marc E
Published: March 2003

Akoad M, Giraldo M, Monaco AP, Hanto DW, Uknis ME. Enteric drainage of a pancreas allograft is safe for patients with celiac sprue. Clin Transplant 2002: 16: 387–388. © Blackwell Munksgaard, 2002

Enteric drainage of exocrine secretions in whole organ pancreas transplantation is generally avoided in patients with pre‐existing small bowel disease; however, bladder drainage is associated with a 20% rate of urinary tract‐related complications. This is a case report of a type 1 diabetic patient with celiac sprue and renal failure. We performed a simultaneous cadaveric kidney pancreas transplant enterically draining the exocrine pancreas. There were no complications. The patient is now more than 6 months post‐transplant with excellent function of both renal and pancreas allografts. We conclude that enteric drainage of pancreas allografts in patients with celiac sprue may be performed safely.

Whole organ pancreas transplantation is being performed with greater success than ever before, mostly as a result of lessons learned from past experience (1). Enteric drainage of allograft exocrine secretions is preferred for simultaneous pancreas/kidney (SPK) recipients to avoid urinary tract complications associated with bladder drainage. However, most agree that diabetics with pre‐existing bowel disease should have bladder drainage of allograft exocrine secretions, so as to prevent the devastating complication of a bowel leak. We describe here a successful case of enteric drainage of an SPK transplant in a patient with celiac sprue. We believe that, when carefully performed, enteric drainage of pancreas allografts is a safe approach for diabetic patients with celiac sprue, and may avert the serious complications associated with bladder drainage.
Concomitant intramyocardial and epicardial vasculitis in an autopsied heart allograft for cardiac rhabdomyosarcoma
Authors: Chang Yih‐Leong , Lin Chien‐Yu , Wang Shoei‐Shen , Kuo Kuan‐Ting , Lee Yung‐Chie , Wu Chen‐Tu
Published: March 2003

Chang Y‐L, Lin C‐Y, Wang S‐S, Kuo K‐T, Lee Y‐C, Wu C‐T. Concomitant intramyocardial and epicardial vasculitis in an autopsied heart allograft for cardiac rhabdomyosarcoma. Clin Transplant 2002: 16: 461–464. © Blackwell Munksgaard, 2002

Primary cardiac tumours are rare, with only one quarter of the patients being malignant. The vast majority of malignant neoplasms of the heart are sarcomas. We describe a patient of primary cardiac rhabdo‐myosarcoma presented as coronary artery disease and recurrent myocardial infarction. Histopathologic finding of the excised native heart revealed a high grade pleomorphic rhabdomyosarcoma in the myoepi‐cardial portion of the anterior wall with rupture. The accompanying unusual feature was myocardial infarction because of tumour emboli of the left anterior descending and left circumflex coronary arteries. After transplantation, the patient developed mild to moderate acute cellular rejection of the transplanted heart on post‐transplantation day 1, 8, and 44, respectively. Unfortunately, he expired on the post‐transplantation day 47 because of acute rejection, presenting as concomitant intramyo‐cardial and epicardial lymphocytic vasculitis and multifocal myocardial ischaemia. We found that this uncommon medial lymphocytic vasculitis lesion was mediated by T cells and also by antibody directly against smooth muscle cells of small arteries. The consequence of such immune response would be compromised myocardial oxygenation resulting in allograft failure.
A standardized protocol for the treatment of severe pneumonia in kidney transplant recipients
Authors: Sileri Pierpaolo , Pursell Kenneth J , Coady Noreen T , Giacomoni Alessandro , Berliti Stefano , Tzoracoleftherakis Evangelos , Testa Giuliano , Benedetti Enrico
Published: March 2003

Abstract:  Although the incidence of pneumonia after kidney transplantation is the lowest among all solid organ transplants, it is associated with high mortality rate (40–50%). We evaluated the efficacy of a protocol consisting of bronco‐alveolar‐lavage (BAL) for early microbiological diagnosis, reduction of the immunosuppressive therapy, and prompt administration of standardized antibiotic regimen in renal transplant recipients with severe pneumonia. Between 6/1989 and 5/1999, 40 kidney transplant recipients developed 46 episodes of severe pneumonia (hypoxia and/or infiltrate on the chest X‐ray). According to protocol, in all these cases, a BAL was immediately performed and empirical antibiotic therapy was initiated with erythromycin and trimethoprim‐sulfamethoxazole i.v. Furthermore, the immunosuppressive therapy was drastically reduced. Analyses of BAL fluid included cell differential count, cytopathologic examination and cultures for bacteria, fungi and viruses. Within 48 h, the therapy was switched to proper i.v. antibiotics, if necessary, according to the results of sensitivity testing of BAL specimens. The mortality rate was 12.5% (5 of 40). Mechanical ventilation was required in 20 cases (34.5%) and four of the patients that required intubation died. BAL alone established a diagnosis in 67.4% (31 of 46) of the patients. Bacteria were responsible for 61% of the episodes, with fungi responsible for 29% and viruses for 10%. Seven cases of Pneumocystis carinii pneumonia were treated with the prolongation of the initial therapy. We conclude that a combination of early detection of the responsible pathogen by BAL, aggressive reduction of the immunosuppressive therapy and the immediate empirical administration of erythromycin and trimethoprim‐sulfamethoxazole is an effective strategy to treat pneumonia kidney transplantation (KTX) recipients.
The apo A‐I gene promoter region polymorphism determines the severity of hyperlipidemia after heart transplantation
Authors: González‐Amieva Angel , López‐Miranda José , Marín Carmen , Pérez‐Martinez Pablo , Gómez Purificación , Paz‐Rojas Elier , Arizón Josè M. , Jiménez‐Perepérez José A. , Concha Manuel , Pérez‐Jiménez Francisco
Published: March 2003

Abstract: Background: To study whether the Apolipoprotein A‐I (apo A‐I) promoter region gene polymorphism produces changes in the lipid profile of heart transplant recipients.

Methods: One hundred and three heart transplant recipients (93 men and 10 women, with a mean age of 47 ± 13 yr) receiving triple immunosuppressive therapy were submitted to a genetic study of the apo A‐I gene promoter region. Anthropometric and analytical data, including lipid profile, arterial blood pressure, were collected prior to transplantation and 3, 6, 12, and 24 months after transplantation.

Results: Sixty‐three subjects had the GG genotype and 40 the GA genotype. Carriers of the GA genotype had higher triglyceride levels at 6 months and 2 yr (2.50 ± 1.20 versus 1.93 ± 0.98 mmol/L and 2.46 ± 1.58 versus 1.60 ± 0.68 mmol/L, respectively, p < 0.001), and a greater rise in LDL‐cholesterol at 1 yr than the GG subjects (4.57 ± 1.16 versus 4.16 ± 1.18 mmol/L, p < 0.05). Multiple regression analyses showed that genetic variants at the apo A‐I promoter region are responsible for 11% of the variability in triglyceride levels at 6 months (p = 0.005).

Conclusions: The GA genotype of the apo A‐I promoter region produces a greater rise in plasma triglyceride and LDL‐cholesterol levels in heart transplant patients.
Repetitive transcranial magnetic stimulation: perspectives for application in the treatment of bipolar and unipolar disorders
Authors: Nahas Ziad , Molloy Monica A , Hughes Patrick L , Oliver Nicholas C , Arana George W , Risch S Craig , George Mark S
Published: March 2003

Objectives:

Transcranial magnetic stimulation (TMS) affects the brain by non‐invasively stimulating the cerebral cortex and inducing electrical currents in neurons. The powerful magnetic field acts as a vector that passes across the scalp and the skull, and then converts into an electrical energy within the brain. Originally used in neurophysiology, TMS has since been applied in a variety of neuropsychiatric conditions, including mood disorders. Imaging studies in mood‐disordered patients have pointed to dysfunctional limbic and prefrontal cortex activity. TMS researchers have thus postulated that dorsolateral prefrontal cortex (DLPFC) stimulation might change brain activity both locally and in paralimbic areas through transynaptic connections, and alter mood.   Methods: We will describe the technology of TMS, its applications to date, and explore its mechanisms of action.   Results: Several clinical trials have demonstrated TMS effects on mood in health and disease. There is a growing consensus that TMS has antidepressant effects, although little is known about the role played by a variety of stimulation parameters such as the intensity or frequency of stimulation. One study has found an antimanic effect of right prefrontal TMS.   Conclusion: TMS is relatively safe; however, much more research is needed before TMS can be integrated into routine clinical practice.
Abnormalities of cAMP signaling in affective disorders: implications for pathophysiology and treatment
Authors: Perez Jorge , Tardito Daniela , Mori Silvia , Racagni Giorgio , Smeraldi Enrico , Zanardi Raffaella
Published: March 2003

Objective:

During the last decade, much attention has been given to the role of signal transduction pathways in affective disorders. This review describes the possible role of the cAMP signaling in such disorders.   Methods: Among the components of cAMP signaling, this review focuses on the cAMP‐dependent phosphorylation system. We analyzed the basic components of the cAMP‐dependent phosphorylation system and the preclinical evidence supporting their involvement in the biochemical action of antidepressants and mood stabilizers. The clinical data available until now, concerning the possible link between the cAMP‐dependent phosphorylation system and the pathophysiology of affective disorders, are also reviewed.   Results: The studies herein presented demonstrated that the levels and the activity of cAMP‐dependent protein kinase are altered by antidepressants and mood stabilizers. Furthermore, these medications are able to modify the phosphorylation state, as well as the levels of some of the cAMP‐dependent protein kinase substrates. More recently, clinical studies have reported abnormalities in the cAMP‐dependent phosphorylation system in both peripheral cells and the postmortem brain of patients with affective disorders.   Conclusions: Overall, these studies support an involvement of cAMP signaling in affective disorders. The precise knowledge of the findings has the potential to improve the understanding of pharmacotherapy and to provide directions for the development of novel biochemical and genetic research strategies on the pathogenesis of affective disorders.
Psychotropic drug prescription patterns among patients with bipolar I disorder
Authors: Levine Joseph , Chengappa Kn Roy , Brar Jaspreet S , Gershon Samuel , Yablonsky Eric , Stapf Deborah , Kupfer David J
Published: March 2003

Introduction:

Combination treatment, rather than monotherapy, is prevalent in the treatment of subjects with bipolar disorder, probably due to the complex and phasic nature of the illness. In general, prescription patterns may be influenced by the demographic characteristics of patients as well. We evaluated prescription patterns and the influence of demographic variables on these patterns in a voluntary registry of subjects with bipolar disorder.   Methods: A subset of data from a larger voluntary registry was extracted for demographic variables and psychotropic medication use that had been reported in the month prior to registration by ambulatory, non‐hospitalized subjects with bipolar I disorder in 1995/96 (n=457).   Results: Among the thymoleptic agents, lithium was prescribed in over 50% of subjects, valproate in approximately 40%, and carbamazepine in 11% of subjects. Eighteen percent of subjects had no prescription for thymoleptic agents. Nearly one‐third of all subjects were receiving antipsychotic agents, of whom two‐thirds were receiving the traditional neuroleptic agents. More than half of all subjects were receiving concomitant antidepressants, of whom nearly 50% received the SSRI antidepressants and nearly 25% received buproprion. Approximately 40% of subjects received benzodiazepines. Only 18% of subjects received monotherapy, and nearly 50% received three or more psychotropic agents. In general, no associations were noted between demographic parameters including age, gender, marital or educational status, and psychotropic prescriptions.   Conclusion: Consistent with the anecdotal reports, these data confirm that combination treatment is far more common than monotherapy. Demography appears to have a minimal impact on cross‐sectional prescription patterns in subjects with bipolar disorder. Given that combination treatments are the rule rather than the exception, we should strive to achieve rational, yet pragmatic, treatment guidelines and algorithms to minimize the risks while maximizing the benefits of these combination treatments for patients with bipolar disorder.
An open longitudinal study of patients with bipolar rapid cycling treated with lithium or lamotrigine for mood stabilization
Authors: Walden Joerg , Schaerer Lars , Schloesser Sandra , Grunze Heinz
Published: March 2003

Objectives:
Patients with rapid cycling bipolar disorder are frequently observed to fail conventional treatment. We conducted a preliminary study to explore the potential efficacy of lamotrigine in the treatment of this refractory patient population.   Methods: In an open longitudinal investigation, 14 patients with rapid cycling bipolar disorder were treated for 1 year with either lithium or lamotrigine as mood stabilizer.   Results: Out of the seven patients with lithium, three out of seven (43%) had less than four and four out of seven (57%) had four or more episodes. In the lamotrigine group, six out of seven (86%) had less than four and one out of seven (14%) had more than four affective episodes (depressive, manic, hypomanic or mixed). In fact, three out of seven (43%) of the patients who were on lamotrigine therapy were without any further affective episodes. There was no evidence of a preferential antidepressant versus antimanic efficacy.   Conclusions: Although the study is limited by the small number of patients, the results are in line with other investigations, suggesting efficacy for lamotrigine and a suboptimal response for lithium in rapid cycling bipolar disorder. These preliminary data need to be confirmed with controlled double blind studies.
Choline, myo‐inositol and mood in bipolar disorder: a proton magnetic resonance spectroscopic imaging study of the anterior cingulate cortex
Authors: Moore Constance M , Breeze Janis L , Gruber Staci A , Babb Suzann M , DeB Frederick Blaise , Villafuerte Rosemond A , Stoll Andrew L , Hennen John , Yurgelun‐Todd Deborah A , Cohen Bruce M , Renshaw Perry F
Published: March 2003

Objectives:

Alterations in choline and myo‐inositol metabolism have been noted in bipolar disorder, and the therapeutic efficacy of lithium in mania may be related to these effects. We wished to determine the relationship between anterior cingulate cortex choline and myo‐inositol levels, assessed using proton magnetic resonance spectroscopic imaging (MRSI), and mood state in subjects with bipolar disorder.

  Methods: Serial assessments of anterior cingulate cortex choline and myo‐inositol metabolism were performed in nine subjects with bipolar disorder, taking either lithium or valproate, and 14 controls. Each bipolar subject was examined between one and four times (3.1±1.3). On the occasion of each examination, standardized ratings of both depression and mania were recorded.

  Results: In the left cingulate cortex, the bipolar subjects’ depression ratings correlated positively with MRSI measures of Cho/Cr‐PCr. In the right cingulate cortex, the Cho/Cr‐PCr ratio was significantly higher in subjects with bipolar disorder compared with control subjects. In addition, bipolar subjects not taking antidepressants had a significantly higher right cingulate cortex Cho/Cr‐PCr ratio compared with patients taking antidepressants or controls. No clinical or drug‐related changes were observed for the Ino/Cr‐PCr ratio.

  Conclusions: The results of this study suggest that bipolar disorder is associated with alterations in the metabolism of cytosolic, choline‐containing compounds in the anterior cingulate cortex. As this resonance arises primarily from phosphocholine and glycerophosphocholine, both of which are metabolites of phosphatidylcholine, these results are consistent with impaired intraneuronal signaling mechanisms.
Health care utilization and costs among privately insured patients with bipolar I disorder
Authors: Bryant‐Comstock Lynda , Stender Monika , Devercelli Giovanna
Published: March 2003

Objective:  This study examined health care resource utilization and direct health care costs among patients diagnosed with bipolar I disorder in a privately insured population.

Methods:  Health care claims data for 2883 patients with a primary diagnosis of bipolar disorder were compared over a 1‐year period (1997) with claims data for 2883 randomly selected, age‐ and sex‐matched, non‐bipolar patients, all covered under the same large private insurer in USA. Resource use (i.e. original and refill pharmaceutical dispensing, medical and procedural services received, inpatient hospitalization, outpatient services, physician visits and emergency room treatment) and their costs are described overall, as well as by bipolar disorder diagnosis (based on ICD‐9 codes) and type of care (i.e. mental health versus non‐mental health).

Results:  Bipolar patients utilized nearly three to four times the health care resources and incurred over four times greater costs per patient compared with the non‐bipolar group during the 1‐year period ($7663 versus $1962). Inpatient care (hospitalizations) accounted for the greatest disparity between groups, as it was the single‐most costly resource in the bipolar group ($2779 versus $398). Patients with bipolar depression (among the single bipolar diagnostic categories of mixed, manic or depressed) incurred the highest health care costs. While mental health care cost was a significant component of total cost in the bipolar group, it accounted for only 22% of the total per‐patient cost; in comparison, it accounted for only 6% of the total per‐patient cost in the non‐bipolar group.

Conclusion:  Treatment of bipolar disorder, particularly inpatient care, is costly to patients and health insurers. Further study is needed to find ways to reduce the overall cost of managing these patients without jeopardizing patient care.
Impact of concurrent alcohol misuse on symptom presentation of acute mania at initial evaluation
Authors: Salloum Ihsan M , Cornelius Jack R , Mezzich Juan E , Kirisci Levent
Published: March 2003

Objectives:  The aim of this study was to evaluate the impact of current alcohol misuse on symptom presentation of acute mania.

Methods:  The impact of concurrent alcohol misuse on symptom presentation of acute mania was examined by comparing comorbid subjects with acute bipolar mania complicated by current alcohol misuse (n=60) with subjects with acute bipolar mania without current alcohol misuse (n=196).

Results:  Age‐ and gender‐controlled analysis revealed that the comorbid group presented with more severe psychopathology, as indicated by higher number of total mood‐related symptoms as well as of higher total number of manic symptoms. Specifically, they presented with significantly higher rates of mood lability and impulsivity, and also demonstrated higher rates of violent behavior, and other drug use.

Conclusions:  Acute mania complicated by current alcohol misuse is differentiated from acute mania without alcohol misuse by the presence of higher numbers of manic symptoms and increased high risk behavior such as mood lability, impulsivity, violence, and other drug abuse.