bluuebunny/crossref_metadata_2025 huggingface dataset:
SCA8 in the Spanish population including one homozygous patient
Authors: Tazón B , Badenas C , Jiménez L , Muñoz E , Milà M
Published: March 2003

Controversial data have been reported about SCA8 since its description in 1999. The most accepted hypothesis is that CTG expansions within the CTA/CTG combined repeat expansion in the SCA8 locus causes SCA8. It is inherited as a dominant trait with reduced penetrance. The present study, reports the first data regarding SCA8 in the Spanish population and the clinical findings in patients carrying expanded alleles, including one homozygous patient. Two hundred and forty‐six individuals from the Spanish population,

including controls (149) and ataxic patients (97), were studied. DNA was extracted from blood samples using standard methods. Amplification of the CTA/CTG 3′untranslated region was achieved by PCR using primers SCA8‐F3 and SCA8‐R4 and conditions described previously. Neurological revaluation was done in individuals carrying the expanded allele. We detected five unrelated expanded alleles corresponding to three affected patients (one of them homozygous) and one healthy individual. SCA8 represents 4% of the total dominant spinocerebellar ataxias studied in our group (Spanish population) (three index patients out of 75 dominant ataxic independent nucleus). The patient that resulted homozygous for the expansion is a 25‐year‐old man with a clinical picture of progressive ataxia and dysarthria that began at the age of 12. On neurological examination, he showed ataxia, slight dysarthria and nystagmus to the extreme lateral gaze. A cranial MRI showed global atrophy of cerebellum but the brainstem was spared. Family history showed the presence of ataxia in his grandfather and father. His mother is healthy at the age of 52 and a molecular study of SCA8 reveals one allele that could be considered as premutated. She has no ataxia antecedents in her family. Our results provide additional information about the SCA8 expansion, within the Spanish population. These results are in agreement with the hypothesis of the CTG expansion in the SCA8 locus being responsible for the SCA8 ataxia showing reduced penetrance. Besides homozygous status, advancing age at onset (as previously described for other SCAs) supports this idea.
Genetic origins in a South American clefting population
Authors: Vieira AR , Karras JC , Orioli IM , Castilla EE , Murray JC
Published: March 2003

Vieira AR, Karras JC, Orioli IM, Castilla EE, Murray JC. Genetic origins in a South American clefting population.  Clin Genet 2002: 62: 458–463. © Blackwell Munksgaard, 2002

It has been proposed that susceptibility to clefting in South America is related to Amerindian ancestry, where clefting is present at a higher frequency than in the other admixed populations (Caucasian and African) that make up the diverse racial mix of current South Americans. To clarify the genetic origins and establish a method for genetic mapping, mitochondrial DNA variation and Y‐chromosome markers were studied in a South American population affected with clefting. Two‐hundred and seventeen subjects and matched controls were selected through the Latin‐American Collaborative Study of Congenital Malformations (ECLAMC). The case group showed a higher frequency of Native American haplogroups and a lower frequency of African haplogroups (p < 0.00001). In addition, the case group showed a much higher frequency of the specific native American haplogroup D than the control group (p < 0.00001). For the Y‐chromosome markers, the case group showed a lower frequency of the African‐specific marker, YAP (p = 0.002), and a higher frequency of the Native American‐specific marker, DYS199 (p < 0.00001). Even though differences were found in the frequencies of the markers studied, the contribution of each founder population was similar for both groups. Results suggest a strong Native American maternal contribution and a strong Caucasian (Spanish and Portuguese) paternal contribution to the population studied. The implications of this finding include the possibility of using admixture mapping approaches to this population.
Expression of Γ‐IFN mRNA in bronchoalveolar lavage fluid correlates with early acute allograft rejection in lung transplant recipients
Authors: Moudgil A , Bagga A , Toyoda M , Nicolaidou E , Jordan SC , Ross D
Published: March 2003

Various cytokines are upregulated in acute allograft rejection (AR). Local production of Th‐1 cytokines is suggested to play a pathogenic role in AR, and Th‐2 cytokines in the development of allograft tolerance. The purpose of this study was to correlate the expression of Th‐1 [interleukin‐2 (IL‐2) and Γ‐interferon (Γ‐IFN)], and Th‐2 [interleukin‐10 (IL‐10)] cytokines in bronchoalveolar lavage (BAL) fluid with AR in lung transplant (LT) recipients. The role of Th‐1 dominance expressed as IgG2/IgG1 ratio in BAL in AR was also examined. The mRNA expression for IL‐2, Γ‐IFN and IL‐10 was examined in 64 BAL specimens from 23 LT recipients using reverse transcriptase‐polymerase chain reaction (RT‐PCR). IgG1 and IgG2 levels were measured in 55 BAL specimens by enzyme‐linked immunosorbent assay (ELISA). The expression of mRNA for these cytokines, and the ratio of IgG2/IgG1 was correlated with AR (early AR occurring within 3 months of transplant and late AR occurring after 3 months). Ten patients had 17 episodes of biopsy proven AR. Twelve episodes of AR (6 patients) occurred within the first 3 months of transplantation. In 5 patients, AR was diagnosed 4, 5, 6, 9 and 24 months post‐transplantation. Detection of Γ‐IFN mRNA correlated significantly with early AR (p<0.001), whereas it lacked correlation with late AR. Expression of IL‐2 and IL‐10 mRNA did not correlate with AR. IL‐10 was present in most samples irrespective of the presence or absence of AR. The ratio of IgG2/IgG1 was similar in patients with or without AR. Our findings suggest that the detection of Γ‐IFN mRNA in BAL by RT‐PCR is useful for immune monitoring of early AR in LT recipients. Absence of elevated IgG2/IgG1 ratio, and presence of IL‐10 in BAL during AR suggests that Th‐1 cytokines may not be the sole mediator of rejection in LT recipients.
Influence of hyperglycemia and hyperuricemia on long‐term transplant survival in kidney transplant recipients
Authors: Gerhardt U , Große Hüttmann M , Hohage H
Published: March 2003

Long‐term prognosis in kidney transplant recipients depends on multiple factors. The purpose of this study was to quantify the influence of hyperuricemia and hyperglycemia (elements of the so‐called ‘syndrome X’, i.e., a combination of metabolic disorders like hyperuricemia, diabetes mellitus, hyperlipidemia, and hypertension) on organ function in 350 kidney transplant recipients who had received 375 kidney transplants up to 1990 and in whom sex, age of recipient and donor, nephrologic disease, duration of dialysis, human leukocyte antigen (HLA) classification, and duration of transplant ischemia had been well matched. We found the influence of hyperuricemia on graft survival to be statistically significant (p≤0.05), while a statistically significant correlation between hyperglycemia and graft survival could not be detected in the present study. The transplant survival rates 2, 4, and 5 yr post‐kidney‐transplantation were 96.7, 80.7, and 78.7 in normogylcemic patients vs. 96.9, 85, and 82.7% in hyperglycemic (>100 mg/dL) kidney transplant recipients (p>0.05). Transplant survival in hyperuricemic patients (male,> 8 mg/dL; female,> 6.2 mg/dL) 2, 4, and 5 yr post‐transplantation was significantly reduced (92.2, 70.6, and 68.8% vs. 98.1, 85.6, and 83.3%), as compared to normouricemic recipients. A combined presence of both hyperuricemia and hyperglycemia probably influencing the prognosis post‐kidney‐transplantation failed to reach the level of statistical significance. We found a significant correlation between age of recipients and plasma glucose (p≤0.01) and between serum uric acid concentrations and diuretic therapy (p≤0.05) and gender (p≤0.05).

In conclusion, hyperuricemia after kidney transplantation seems to reduce graft survival, whereas an influence of the carbohydrate metabolism has to be denied.
Changes in liver regenerative factors in a case of living‐related liver transplantation
Authors: Eguchi Susumu , Okudaira Sadayuki , Azuma Takashi , Ohno Yasuharu , Fujioka Hikaru , Furui Junichiro , Tanaka Koichi , Kanematsu Takashi
Published: March 2003

Liver regeneration in a patient with fulminant hepatic failure (FHF) who underwent living‐related partial liver transplantation (LRLT) was investigated regarding hepatic growth factors. The patient was a 16‐yr‐old Japanese male who developed severe subacute FHF. LRLT was performed using an extended left lobe of the ABO matched patient's mother. In the recipient, the pre‐transplant levels of both plasma hepatocyte growth factor (HGF) and transforming growth factor (TGF)‐β were extremely high and rapidly decreased following the liver replacement. The liver volume evaluated using a CAT scan increased 195% after 2 wk in graft liver and 110% after 2 wk in the hepatectomized donor. The explanted liver (FHF liver), the liver from donor (normal liver), and the graft liver [the 3rd post‐transplant day (POD 3)] were all investigated immunohistochemically. FHF liver: No liver regeneration was observed [proliferative cell nuclear antigen (PCNA) labeling index (L.I.): 0%]. In the liver, both HGF in the hepatocytes and c‐met on the membrane of the hepatocytes were positive. TGF‐β was positive in the hepatocytes and no apoptosis was detected by the TUNEL method. Donor liver (POD 0): Few PCNA stained hepatocytes were detected. No HGF was detected but c‐met was clearly detected on the cell membrane of the hepatocytes. Neither TGF‐β nor apoptosis was detected. Graft liver (POD 3): The PCNA L.I. was conspicuous at 40%. HGF was positive in non‐parenchymal cells and c‐met was positive in the cytoplasm of the hepatocytes. TGF‐β was negative while apoptosis was positive in the zone 3 hepatocytes. In conclusion, these findings suggested that the liver of the patient with FHF did not respond to liver regenerative stimulus, in part, through involvement of inhibitor TGF‐β. On POD 3, the transplanted graft was in a vigorous regenerative status in comparison to that in the hepatectomized donor. The HGF/c‐met system is thought to be involved in the mechanism of regeneration. Intrahepatic apoptosis was detected in the graft on the 3rd post‐transplant day probably due to transient ischemia in the liver, which was not related to the Fas/Fas‐ligand system.
A case of fever of unknown origin with severe stomatitis in renal transplant recipient resulting in graft loss
Authors: Katafuchi Ritsuko , Saito Shoichiro , Yanase Tetsuro , Ikeda Kiyoshi , Hirano Tatsuya , Mizumasa Tohru , Fujita Emi , Tanaka Hiroshi , Fujimi Satoru
Published: March 2003

We present a case of fever of unknown origin and life‐threatening stomatitis developed about 60 months after renal transplantation. He was 15 yr old at the transplantation. Bacterial, fungal, and viral infections were not evident. Fever and stomatitis were resistant to acyclovir and to any anti‐bacterial or anti‐fungal treatment. Graft biopsy revealed a small focus of acute vascular rejection, but the findings were not severe enough to be an etiology of the fever in this case. The administration of cyclosporine (CYA) was stopped 19 d before graftectomy, but the clinical picture was unchanged. Fever and stomatitis was resolved immediately after graftectomy and the discontinuation of immunosuppressants such as mizoribine (MZ) and prednisolone. Pathological changes of the graft included chronic transplant glomerulopathy, acute glomerulitis, and lymphocyte infiltration in peritubular capillaries. Thus we suppose that immunosuppressants were the cause of both fever and stomatitis in this case. We speculate that a fever in this case might be due to the immunosuppressant itself, i.e., CYA or MZ, or viral infection – probably herpes‐simplex virus infection. It is probably the immunosuppressive state per se that may cause the resistance of his muco‐cutaneous lesion to anti‐viral agent.
Comparing quality of life following liver transplantation for Laennec's versus non‐Laennec's patients 1
Authors: Cowling T , Jennings LW , Jung GS , Goldstein RM , Molmenti E , Gonwa TA , Klintmalm GB , Levy MF
Published: March 2003

The overall success of orthotopic liver transplantation (OLTX) includes not only survival, but quality of life (QOL) as well. We studied one controversial group of OLTX recipients, patients transplanted for alcoholic liver disease (Laennec's), to determine if their post‐OLTX QOL was similar to that of patients transplanted for non‐alcoholic liver disease (non‐Laennec's). Over a 10‐yr period, patients undergoing OLTX at our institution were asked to complete a QOL questionnaire addressing a wide range of topics from demographics and employment to symptom distress/frequency, activities of daily living, and effect of loss of health on daily life. Twenty‐four Laennec's and 100 non‐Laennec's OLTX recipients completed the questionnaire at both their 2‐ and 5‐yr follow‐up visits at our institution. Both groups were well‐matched in age, race, and patient location status at the time of OLTX. No significant differences could be detected between Laennec's and non‐Laennec's scores regarding overall QOL, including one's ability to function, health perception, and self‐perception at 2 and 5 years post‐OLTX, and between 2 and 5 years post‐OLTX. Although not between groups, a significant difference was noted regarding patients’ satisfaction with life, with less satisfaction reported at the 5‐yr versus the 2‐yr time point post‐OLTX. Rates of current/recent employment between both groups were also similar at 2 years post‐OLTX, and again at 5 years post‐OLTX. We conclude that overall QOL and employment levels appear similar between patients transplanted for alcoholic and non‐alcoholic liver disease. This similarity appears to extend to 5 years post‐OLTX.
Effect of recipient sensitization (peak PRA) on graft outcome in haploidentical living related kidney transplants
Authors: Barama A , Oza U , Panek R , Belitsky P , MacDonald As , Lawen J , McAlister V , Kiberd B
Published: March 2003

Objective. To evaluate the influence of pre‐transplant recipient sensitization on the outcome of 1‐haploidentical live related donor (LRD) kidney transplants.  Method. We reviewed 141 consecutive cyclosporine‐treated adult haploidentical first transplants for which panel reactive antibody (PRA) levels were available. Patients were divided into three groups according to their peak PRA levels: group I, PRA=0 (n=97); group II, PRA =1–50% (n=24); and group III, PRA=51–100% (n=20).  Results. Differences in PRA were associated with significant differences in short‐ and longer‐term graft survival, unrelated to patient survival. Graft survival at 1, 3, and 5 yr was only 74, 40, and 27% in group III, compared to 92, 87, and 52% in group II, and 96, 91, and 85% in group I (p<0.001). Increasing PRA was associated with shorter time‐to‐graft failure. In group III, 20% lost their transplant from acute rejection in the first 6 months, versus 4% in group II and 3% in group I (p<0.01). Graft survival in group II diverged from that of group I only after 3 yr, due to an increase in loss from chronic rejection. Hospitalization was longer in group III, in association with a significantly higher incidence of acute rejection during the first 3 months after transplantation (p<0.02). Serum creatinine was higher in sensitized than nonsensitized patients at all time points.  Conclusions. Sensitization has a significant negative impact on the outcome of haploidentical LRD kidney transplants. Sensitized potential recipients and their potential donors should be aware of this in arriving at informed decision‐making for transplantation. These patients may benefit from more sensitive cross‐match testing, more intense or more novel immunosuppression, or immunomodulation to modify their immune responsiveness.
Chronic cyclosporin nephropathy: long‐term effects of cyclosporin on renal allografts
Authors: Takeda Asami , Uchida Kazuharu , Haba Toshihito , Tominaga Yoshihiro , Katayama Akio , Yoshida Atsuhiro , Oikawa Tadashi , Morozumi Kunio
Published: March 2003

Takeda A, Uchida K, Haba T, Tominaga Y, Katayama A, Yoshida A, Oikawa T, Morozumi K. Chronic cyclosporin nephropathy: long‐term effects of cyclosporin on renal allografts. Clin Transplantation 2001: 15 (Supplement 5): 22–29. ©Munksgaard, 2001.

Cyclosporin (CSA) has significantly reduced both incidence and severity of acute rejection, and brought excellent graft survival rates. Chronic CSA nephrotoxicity seems to be the second most important diagnosis responsible for the late graft failure. CSA‐associated arteriolopathy (CAA) is well known as a characteristic lesion of chronic CSA nephrotoxicity by graft biopsies. There are few reports on the long‐term outcome of renal transplant patients with biopsy‐proven chronic CSA nephrotoxicity after diagnosis of CAA. We conducted two studies, the long‐term outcome of the patients with CAA, and the FGS lesion related to CAA. Seventy‐four CAA patients continued on CSA therapy after diagnosis of CAA were classified into two groups by outcome of the graft after follow‐up: the functioning graft group (n=30) and the graft‐loss group (n=44). There was no significant difference in severity of CAA grade between the functioning and graft‐loss groups. Concomitant lesion of chronic rejection but not severity of CAA was the most important risk factor of graft loss for CAA patients in our study. Of a total of 54 recipients with FGS lesion, 32 patients (59%) were diagnosed as CAA‐associated glomerulopathy (CAG) accompanied with severe CAA. Eighteen of 32 CAG patients lost their grafts after follow‐up. Their serum creatinine level at biopsy was higher than that of the functioning group; however, there was no significant difference in daily proteinuria at biopsy between two groups. We have tried to reduce CSA dosage to maintain lower blood levels than the usual optimal target levels, but did not discontinue CSA after diagnosis of severe CAA and FGS lesion. In 15 isolated pure CAG patients, those with increasing daily proteinuria exceeding 2 g lost their graft function even after reducing CSA administration. The change in daily proteinuria seems to be a useful indicator for late graft loss in the patients of FGS lesion with severe CAA. CAA is not specific for chronic CSA nephrotoxicity, and FGS lesion is also a non‐specific lesion often developed in renal allografts. Our study revealed clinicopathological characteristics of chronic CSA nephrotoxicity. Isolated chronic CSA arteriolopathy of severe degree has a fairly good prognosis under controlled CSA therapy. FGS lesion accompanied by CAA is considered as a new concept of CAG, and increasing proteinuria in patients with CAG is a good indicator for poor outcome. These results will contribute towards an appropriate therapeutic plan for renal transplant patients undergoing long‐term CSA treatment.
Clotrimazole increases tacrolimus blood levels: a drug interaction in kidney transplant patients
Authors: Vasquez Em , Pollak R , Benedetti E
Published: March 2003

In order to substantiate a previous case report of a drug interaction between tacrolimus and clotrimazole, we randomly assigned tacrolimus‐treated renal allograft recipients to therapy with either clotrimazole or nystatin for oral thrush prophylaxis immediately following transplantation. Patients receiving other agents known to interact with cytochrome P450 were excluded from the study. The clotrimazole group consisted of 17 patients and the nystatin group, which served as the control group, consisted of 18 patients. An oral loading dose (∼0.3 mg/kg) of tacrolimus was given pre‐operatively. Post‐transplant, tacrolimus (∼0.15 mg/kg) was orally administered twice daily. Clotrimazole therapy consisted of a 10‐mg troche administered three times daily. Nystatin therapy consisted of the oral suspension (5 mL) administered as a ‘swish and swallow’ four times daily. We evaluated tacrolimus trough blood levels and tacrolimus doses on days 1, 3, 5, and 7 following transplantation. On post‐transplant day 1, mean tacrolimus trough levels did not differ between clotrimazole‐ and nystatin‐treated patients. Mean tacrolimus blood trough levels were significantly higher in clotrimazole‐treated patients on days 3, 5, and 7 post‐transplant, 42±14, 53±7, and 33±17 ng/mL, respectively, compared to 15±8, 15±7, and 14±6 ng/mL in nystatin‐treated patients (p<0.05). The mean tacrolimus dose was significantly lower in the clotrimazole group by day 7 post‐transplant (p<0.05). We conclude that clotrimazole therapy may cause a significant rise in tacrolimus trough blood levels. Recognition of this potential drug interaction is essential to minimize tacrolimus‐associated toxicities in the early post‐transplant period.
Hyperhomocysteinemia and transplant coronary artery disease in cardiac transplant recipients
Authors: Miner Steven ES , Cole David EC , Evrovski Jovan , Verma Atul , Daly Paul A , Ross Heather J
Published: March 2003

Background: In cardiac transplant recipients, long‐term survival may be limited by transplant coronary artery disease (TxCAD). Hyperhomocysteinemia (Hhcy) has been associated with vascular disease and is common in transplant recipients. The objective of this study was to determine the relationship between fasting homocysteine (Hcy) concentrations and TxCAD in a cohort of cardiac transplant recipients.  Methods: Forty‐eight patients more than 5 yr after transplant were recruited from a cohort of 72 consecutive patients with in‐depth analysis of homocysteine levels from the Cardiac Transplant Clinic. Early morning fasting blood was obtained, and the plasma separated and frozen within 30 min. Hcy concentrations were determined by high‐performance liquid chromatography (HPLC) with pulsed integrated amperometry. Coronary angiograms were reviewed in a blinded fashion. TxCAD was diagnosed, using the most recent angiogram, when a >25% lesion was present anywhere in the coronary tree.  Results: Forty‐eight patients transplanted between 1985 and 1994 were studied. The mean Hcy concentration for the cohort was 23.5±5.0 μmol/L, all patients had homocysteine levels above the upper range of normal (5–15 μmol/L). Hcy concentrations were significantly higher in patients with angiographic evidence of TxCAD: 25.0±5.9 vs. 21.9±3.4 μmol/L, p=0.03. This effect persisted when covariates were taken into account using logistic regression analysis.  Conclusions: Hhcy is associated with TxCAD. Prospective studies are required to confirm this association and to assess the efficacy of Hcy‐lowering therapy in this patient population.
Comparison of palpation‐guided and ultrasound‐guided biopsies in transplanted kidneys
Authors: Antonopoulos Ioannis M , Nahas William C , Mazzucchi Eduardo , Ianhez Luiz E , Saldanha Luiz B , Arap Sami
Published: March 2003

Biopsy is the gold standard for the diagnosis of conditions affecting the function of renal allografts. Obtaining representative tissue in biopsies is critical but these procedures are associated with up to 9% of complications and 20% of inadequate material. Although ultrasound guidance allows perfect control of depth and location of the graft, there is controversy regarding the cost–benefit of its use and reports of unsuitable material in ultrasound‐guided biopsies are still high.  Purpose: To compare ultrasound with the palpation method to guide biopsies in order to see if there is any difference between both methods and which one is better.  Patients and methods: The casuistic consisted of 82 renal transplant patients (32 female and 50 male patients, age ranging between 5 and 64 yr; m=31.2 yr) randomized into two groups: GI, palpation‐guided; GII, ultrasound‐guided. Fifty‐six biopsies were performed in GI and 66 in GII.  Results: Number of glomeruli, arcuate, and interlobar arteries and arterioles were compared in the two groups and were 503 (m=10) vs. 801 (m=12.9), 24 (m=0.5) vs. 38 (m=0.6), 104 (m=2.1) vs. 154 (m=2.5), and 174 (m=3.5) vs. 264 (4.3), respectively (p<0.05). Inadequate material for analysis in GI and GII was 7.1 and 7.6%, respectively (p=0.72).  Conclusions: Although ultrasound guidance improves the number of glomeruli, arcuate, and interlobar arteries, as well as arterioles, compared with palpation‐guided biopsies, there is no difference in the rate of adequate material between the two methods.
Plasma exchange and heart–liver transplantation in a patient with homozygous familial hypercholesterolemia
Authors: Offstad Jon , Schrumpf Erik , Geiran Odd , Søreide Odd , Simonsen Svein
Published: March 2003

A female patient born in 1950 underwent plasma exchange and concomitant drug therapy for 20 yr due to homozygous familial hypercholesterolemia. Plasma exchange reduced total cholesterol levels from 25–30 mmol/L (967–1160 mg/dL) before treatment to 9.5 mmol/L (363 mg/dL) with regression of xanthomas and no side effects of long‐term treatment. Due to end‐stage calcific left ventricular outflow tract obstruction not amenable to standard valve reconstructive surgery, a combined heart–liver transplantation was successfully performed in 1996. She is without symptoms and living a normal life 4 yr after transplantation. Total cholesterol value is normal (4.7 mmol/L [182 mg/dL]) using a moderate dose of statins. Selective coronary angiography is without signs of graft vascular disease and the liver function is normal.
Mycobacterium tuberculosis infection and laboratory diagnosis in solid‐organ transplant recipients
Authors: Cavusoglu Cengiz , Cicek‐Saydam Candan , Karasu Zeki , Karaca Yeser , Ozkahya Mehmet , Toz Hüseyin , Tokat Yaman , Bilgic Altinay
Published: March 2003

Tuberculosis (TB) is an unusual infection in transplant recipients. We evaluated (i) the frequency of TB, (ii) the duration to develop the TB infection, and (iii) clinical consequences, in 380 solid‐organ recipients from January 1995 to December 2000. A total of 10 (2.63%) patients (eight renal, two liver transplant recipients) were found to have post‐transplantation TB. The frequency of TB in this patient population is 8.5‐fold higher than the prevalance in the general Turkish population. Tuberculosis developed within 2–33 months after transplantation, with a median of 15 months. In all of these 10 patients, Mycobacterium tuberculosis (MTB) was isolated from the culture. All the patients continued to have low dose immunosuppressive treatment, and also quadriple antituberculosis treatment [isoniazid (INH), rifampin (RIF), pyrazinamide (PRZ) and ethambutol (ETB)] has been given. The two recipients had died of disseminated form of TB. Relapse was detected in one patient 6 months after the completion of the treatment. As post‐transplant TB infection develops mostly within the first year after transplantation, clinicians should be more careful for early and fast diagnosis and treatment should be started immediately.
Psychosomatic interrelations following liver transplantation
Authors: Walter Marc , Moyzes Dierk , Rose Matthias , Neuhaus Ruth , Danzer Gerhard , Klapp Burghard F
Published: March 2003

It is well described that quality of life (QoL) improved after liver transplantation. The aim of the present study was to investigate how psychosocial parameters develop after liver transplantation (LTX) and whether post‐operative complaints are the result of osteoporosis or patient somatization. The prospective study looks into biomedical and psychosocial parameters of 82 LTX patients before, 1 and 3 yrs after transplantation. Osteoporosis was measured by bone mineral density (BMD) and psychosocial parameters were assessed with validated questionnaires measuring complaints, mood and overall QoL. Overall QoL and mood improved after liver transplantation, while back and limb pain increased continuously. Back and limb pain were highly correlated with reduced bone density and high values for tiredness and depressive anxiety. Back and limb pain of patients following liver transplantation may indicate the development of a post‐operative depression in some cases. The treatment offered by an essentially biologically based medicine may promote the manifestation of this depression as a somatization disorder.
Sequential monitoring of intragraft cytokine mRNA expression in relation to diastolic left ventricular wall thickness and function early after heart transplantation
Authors: De Groot‐Kruseman Hester A , Baan Carla C , Hagman Elly M , Mol Wendy M , Niesters Hubert G , Maat Alex P , Vantrimpont Pascal J , Zondervan Pieter E , Weimar Willem , Balk Aggie H
Published: March 2003

Abstract:  Because production of immune regulatory proteins may play a role in early graft dysfunction after heart transplantation, we analyzed whether intragraft cytokine messenger RNA (mRNA) expression levels are associated with diastolic left ventricular function in cardiac allografts. We intensively monitored 16 cardiac allograft recipients during the first 3 months after transplantation. The mRNA expression levels of tumor necrosis factor (TNF‐α), monocyte chemoattractant protein‐1 (MCP‐1), transforming growth factor (TGF‐β), platelet derived growth factor (PDGF‐A), and basic fibroblast growth factor (bFGF) were measured in endomyocardial biopsies (n = 123) by quantitative RT‐PCR. To determine diastolic allograft function, concurrent M‐mode and two‐dimensional Doppler echocardiograms were analyzed for the following parameters: left ventricular total wall thickness, maximal early and atrial mitral flow velocity, deceleration time of maximal early mitral flow velocity, and isovolumetric relaxation period. During the first 3 months post‐transplant an overall decrease in mRNA expression levels of almost all measured cytokines was observed, which paralleled an improvement in diastolic left ventricular wall thickness and function. However, no straightforward relationship could be found between a specific cytokine mRNA expression pattern and the studied echocardiographic parameters. Our data suggest that the improvement in diastolic left ventricular function is associated with a general reduction of inflammation within the allograft, rather than related to a specific cytokine expression pattern.
Valproate treatment and the risk of hyperandrogenism and polycystic ovaries
Authors: Soares Jair C
Published: March 2003

Long‐term administration of valproate to women with epilepsy has been suggested to result in increased risk of hyperandrogenism and polycystic ovaries. In preliminary reports involving patients treated for several years, the reported rates were as high as 43% for polycystic ovaries and 17% for hyperandrogenism. In particular, when therapy started before the age of 20 years, the rates of either one of these complications were as high as 80%. Surprisingly, these reports have been relatively ignored in the psychiatric literature to date. As increasing numbers of bipolar patients are in long‐term treatment with valproate, there is an important need for further research that clarifies the relationship between long‐term administration of valproate and other mood stabilizers and the potential development of reproductive endocrinologic abnormalities, and for increased awareness among clinicians and patients of the unknown potential for these worrisome side‐effects.
The high affinity inositol transport system – implications for the pathophysiology and treatment of bipolar disorder
Authors: Calker Dietrich van , Belmaker Robert H
Published: March 2003

The ‘inositol‐depletion hypothesis’ postulates that the therapeutic effects of lithium are due to inhibition of inositol monophosphatase, which leads to depletion of brain cells of myo‐inositol and consequently to dampening of phosphoinositide (PI) signaling. This article examines the potential relevance of an alternative mechanism for inositol depletion: inhibition of myo‐inositol uptake that proceeds via the sodium/myo‐inositol cotransport (SMIT). We discuss recent in vitro experiments that show a pronounced downregulation of SMIT after chronic treatment with lithium, carbamazepine, and valproate at therapeutically relevant concentrations. It is concluded that downregulation of SMIT could represent a common mechanism of action of mood stabilizers.
Calcium channel antagonists for the treatment of bipolar disorder
Authors: Levy Naomi A , Janicak Philip G
Published: March 2003

Calcium channel antagonists (CCAs) have many clinical applications, including their possible use in the treatment of bipolar disorder. Two justifications for this last application are some overlap in physiological activities of CCAs with those of lithium, and a possible association between bipolar disorder and calcium dysregulation. While the data from earlier studies support the use of verapamil in treating bipolar mania, more recent better‐controlled trials have not. This paper reviews the available body of data regarding CCAs in the treatment of bipolar disorder, concluding there is presently limited support for their efficacy.
Cognitive‐behavioral therapy: applications for the management of bipolar disorder
Authors: Patelis‐Siotis Irene
Published: March 2003

Objectives:
This paper reviews cognitive‐behavioral therapy (CBT) for bipolar disorder (BD). Data on the poor outcome of about 50% of patients diagnosed with BD supports the addition of a psychosocial intervention for the treatment of this recurring disorder. The psychoeducational nature of CBT, the effectiveness of CBT in increasing compliance to pharmacological treatment, and the ability of CBT to prevent relapse in unipolar depression (UD) are well suited to the treatment of BD.   Method: Psychosocial interventions for BD will be briefly reviewed. Individual and group CBT interventions (published and unpublished) will also be reviewed. The significance of comorbid anxiety disorders regarding response to treatment will also be discussed. A review of the treatment protocol with the specific cognitive‐behavioral interventions as applied to BD will be presented. Finally, a case example will be presented to illustrate the application of CBT to BD.   Results: Preliminary results indicate that CBT may be an effective adjunctive, intervention for the treatment of BD. Specifically CBT may be helpful in increasing compliance, improving quality of life and functioning, help early symptom recognition, decrease relapse and decrease depressive symptomatology.   Conclusions: Preliminary data on CBT for BD are promising but more rigorous randomized clinical trials are needed to confirm the efficacy of CBT for BD. An other area of research should be to pursue the understanding of cognitive processes in BD which would allow us to refine and develop CBT interventions unique to this disorder.
The influence of successful prophylactic drug treatment on cognitive dysfunction in bipolar disorders
Authors: Wolf Thomas , Müller‐Oerlinghausen Bruno
Published: March 2003

Background:
 Cognitive variables such as negative self‐evaluations have been discussed as vulnerability factors for depressive syndromes. In the context of bipolar disorders dysfunctional cognitive structures have received little interest as these patients seem to be less disturbed during the euthymic interval than patients with major depression.

Methods:
 In the present study, the self‐esteem of remitted patients with DSM‐III‐R diagnosis of major depression (n=20), bipolar disorder (n=20) and healthy controls (n=20) was measured with the Frankfurt Self‐concept Scale (FSKN).

Results:
 1) Statistical analysis by analysis of variance (ANOVA) showed no significant differences as to age, sex, etc. between the psychiatric groups. The clinical groups showed lower self‐esteem ratings in comparison to healthy controls. 2) Four groups (T1–T4) of remitted patients with bipolar disorders (20 in each group) were successfully maintained on mood stabilizers (lithium or carbamazepine) and classified by the duration of their episode‐free period. T1 included those who were episode‐free for only the week before discharge from hospital. T2 were symptom‐free for <30 months. T3 were episode‐free for >30 months and <60 months. T4 were episode‐free for >60 months. The comparison of their FSKN self‐esteem ratings by ANOVA suggests that self‐esteem improves during successful prophylactic treatment. A posteriori contrasts indicate a normalized self‐esteem after a bipolar episode‐free period of at least 47 months.

Conclusions:
 Dysfunctional cognitions can be demonstrated in unipolar as well as in bipolar patients. Successful episode‐preventive medication with mood stabilizers seems to counteract lowered self‐esteem. Adjunctive cognitive therapy might help to optimize the long‐term course of bipolar disorder.
A double‐blind, placebo‐controlled trial of eicosapentanoic acid in rapid cycling bipolar disorder
Authors: Keck Paul E , Freeman Marlene P , McElroy Susan L , Altshuler Lori L , Denicoff Kirk D , Nolen Willem A , Suppes Trisha , Frye Mark , Kupka Ralph , Leverich Gabriele S , Grunze Heinz , Walden Jörg , Post Robert M
Published: March 2003

Keck Jr PE, Freeman MP, McElroy SL, Altshuler LL, Denicoff KD, Nolen WA, Suppes T, Frye M, Kupka R, Leverich GS, Grunze H, Walden J, Post RM. A double‐blind, placebo‐controlled trial of eicosapentanoic acid in rapid cycling bipolar disorder. Bipolar Disord 2002: 4(Suppl. 1): 26–27. © Blackwell Munksgaard, 2002
Rapid prenatal diagnosis of chromosome aneuploidies by interphase fluorescence in situ hybridization: a one‐year clinical experience with high‐risk and urgent fetal and postnatal samples
Authors: BRYNDORF THUE , LUNDSTEEN CLAES , LAMB ALLEN , CHRISTENSEN BRITTA , PHILIP JOHN
Published: March 2003

Objectives. To evaluate the clinical utility of rapid prenatal and postnatal detection of common chromosome aneuploidies by interphase fluorescence in situ hybridization (FISH) analysis with DNA probes.

Design. Four hundred and seventy‐seven high‐risk and/or urgent amniotic fluid, chorionic villus and fetal and postnatal blood samples were prospectively examined by FISH with probes specific for chromosomes 13, 18, 21, X, and Y and results were reported within 48 hours. All FISH results were followed by conventional chromosome analysis, if possible.

Setting. Cytogenetic service laboratory at the tertiary referral center, Rigshospitalet in Copenhagen.

Main outcome measures. The fraction of clinically significant chromosome aneuploidies that was detected by FISH analysis, and the fraction of terminations that was based on FISH and ultrasound results rather than on conventional cytogenetic results.

Results. The FISH assay detected 76% of the clinically significant chromosome abnormalities as determined by subsequent cytogenetic analysis. Seventy‐two percent of the terminations of the chromosomally abnormal pregnancies were based on FISH and ultrasound results rather than on conventional cytogenetic results.

Conclusion. FISH analysis is a clinically useful adjunctive tool to conventional pre‐ and postnatal cytogenetic analysis. The assay rapidly detects the majority of clinically significant chromosome abnormalities, thus facilitating difficult pre‐ and postnatal clinical decisions.
A hypothesis to explain the occurrence of inner myometrial laceration causing massive postpartum hemorrhage
Authors: HAYASHI MASATOSHI , MORI YOSHIOMI , NOGAMI KEN‐ICHI , TAKAGI YOSHITAKE , YAOI MASAYUKI , OHKURA TAKEYOSHI
Published: March 2003

Background. Inner myometrial lacerations were found in three patients who developed uncontrollable postpartum massive bleeding despite the usual treatment for uterine atony. Because all the patients suffered from hemorrhage shock and their medical status deteriorated, their uteri were surgically removed to stop bleeding. After removal, one of them died. Postpartum hemorrhage was caused by inner myometrial laceration. We hypothesized a cause of inner myometrial laceration, using the three resected uteri, an assumed model of the uterine body, and 34 women.

Methods. The subjects were 37 women, of whom three were patients with inner myometrial laceration, 23 were women without inner myometrial laceration who underwent cesarean section, and 11 were women in the first stage of labor. The three resected uteri were examined both macroscopically and microscopically. We measured the thickness of the wall of the uterine muscle at the widest point of the uterine corpus and the thickness of the myometrial wall at a transverse section of the uterine cervix, as well as the radius of the inner lumen at the widest point of the uterus in 23 women during cesarean section. We also measured the thickness of the myometrial wall at the widest point of the uterine corpus in 11 women at the end of the first stage of labor during ultrasonic examination. The data were then used to estimate the stress on the uterine muscle.

Results. The stress on the uterine cervix was stronger than that on the uterine corpus during labor. When the stress on the uterine muscle is stronger than a specific value, inner myometrial lacerations develop on the right and/or left side of the uterine cervix. These lacerations may involve large vessels.

Conclusions. We have discovered another cause of postpartum hemorrhage which we have named inner myometrial laceration. These lacerations appeared to result from a strong stress on the uterine cervix caused by an abnormal rise in intrauterine pressure during labor.
Perinatal deaths in the Faroe Islands during 1986–95
Authors: JOENSEN FRÓĐI , OLSEN SJÚRĐUR FRÓĐI , HOLM TURIĐ , JOENSEN HØGNI DEBES
Published: March 2003

Objective. To examine causes of perinatal mortality in the Faroe Islands, where it has been increased compared to other Nordic societies.

Method. Cases were classified according to a fetal/obstetric, a fetal/neonatal, and a fetal/obstetric/neonatal classification (classifications C1, C2, and C3, respectively).

Setting. The Faroe Islands 1986–1995; as reference materials were used a) the preceding decade in the Faroes and b) a parallel period in Denmark.

Subjects. We examined all available information regarding each case from hospital records, midwife records, birth certificates, death certificates and autopsy records.

Results. The perinatal mortality was 10.3 per 1,000 total births (83/8,096) compared with 13.7 (102/7,458) in the preceding decade; the fall could be attributed to fewer cases with preeclampsia, antepartum bleedings (C1) and antepartum asphyxia (C2) and the number fell despite an increased occurrence of cases attributed to congenital malformations. Perinatal mortality in Denmark was 8.3 (4,574/550,971), where rates were lower of cases with congenital malformations and fetoplacental dysfunction, but where the rate was higher of cases related to preterm birth (C3).

Conclusions. Although the perinatal mortality rate still is higher in the Faroes than Denmark, the rate had fallen in the Faroes from 1976–85 to 1986–1995. The fall was mainly due to fewer cases attributable to antepartum asphyxia, preeclampsia, antepartum bleedings, and hyaline membrane disease, a pattern compatible with a more efficient perinatal service in the Faroes in the latter period.
Predictive value of a screen for gestational diabetes mellitus: influence of associated risk factors
Authors: JIMÉNEZ‐MOLEÓN JOSÉ J. , BUENO‐CAVANILLAS AURORA , LUNA‐DEL‐CASTILLO JUAN D. , LARDELLI‐CLARET PABLO , GARCÍA‐MARTÍN MIGUEL , GÁLVEZ‐VARGAS RAMÓN
Published: March 2003

Background. There is a need for solid evidence of the relative advantages of universal vs. selective screening for gestational diabetes mellitus. Our study of a broad obstetric population determines the positive predictive value of the 50‐g oral glucose challenge test for screening in the presence and absence of classical gestational diabetes risk factors.

Methods. A retrospective cohort study was carried out with a total of 2,574 pregnant women. Clinical information was obtained from hospital records and each patient's medical history, and gestational diabetes risk factors were quantified for each pregnant woman. The positive predictive value of a screen was determined with respect to the number of risk factors.

Results. Age 30 or over, family history of diabetes, obesity ( BMI≥27) and previous fetal macrosomia were established as the most frequent risk factors. Just over half (54.2%) of our population presented one or more risk factors. Screening covered 75% of the population, and was positive in 15% of the cases. Diagnosis was confirmed in 64 cases, 57 of them at risk, and seven with no risk factors. We obtained an overall positive predictive value of 21.8% (CI 17.3–27.0). This figure increases with the number of risk factors, from 12% for the women with no risk factors, to 40% for those presenting three or more risk factors.

Conclusions. A selective screening program that takes into account the clinical background and characteristics of each pregnant woman allows a high yield of true positives while reducing the possible undesirable effects associated with false positives.
Intrapartum external cephalic version of footling‐breech presentation
Authors: KANETI HAGAI , ROSEN DORON , MARKOV SHLOMO , BEYTH YORAM , FEJGIN MOSHE D.
Published: March 2003

Background. External cephalic version is attempted prior to the onset of labor. Women who present in labor with footling breech presentation are usually delivered by cesarean section. We present our experience of external version in women in labor.

Material and methods. External cephalic version was attempted in thirteen patients in labor with footling breech presentation with the breech out of the pelvis.

Results. The procedure was successful in twelve of the thirteen patients. Ten of them delivered vaginally. There were no maternal or neonatal complications.

Conclusions. It may be reasonable to attempt external cephalic version in patients in labor prior to performing a cesarean section.
Ethical implications of aggressive obstetric management at less than 28 weeks of gestation
Authors: Ahner Regine , Bikas Diana , Rabl Michaela , Al‐Kouatly Huda B. , Krauss Alfred N. , Mccullough Laurence B. , Chervenak Frank A.
Published: March 2003

Background. The purpose of this study is to evaluate the outcome of infants born between 23 and 28 completed weeks of gestational age for whom aggressive obstetric management was performed.

Methods. Prenatal data were collected retrospectively from medical records. Neonatal mortality, early morbidity, and the outcome at one year corrected for postconceptional age (corrected age) were determined.

Results. Ninety‐seven infants were included in the study. Serious early morbidity decreased with increasing gestational age. All the infants born prior to 24 weeks showed serious early morbidity: only 26% of the infants born at 24 weeks or later did. There was a significant decline in mortality with increasing gestational age, as there was also in birth weight (p<0.001, p<0.001). Sixty‐seven percent of the infants prior to 24 weeks showed disability at one year corrected age whereas only 13% at 24 weeks or older did. The likelihood of having a surviving child without disability was 12.5% at 23 weeks, 39% at 24 weeks, 50% at 25 weeks, 52% at 26 weeks, and 70% at 27 weeks.

Conclusion. Viability of fetuses at 23 and 24 weeks of gestation remains ethically and clinically controversial. It cannot be reliably established at that time that there is a fair balance of clinical goods over harms for the survivor at 23 weeks. On the other hand we should continue to treat fetuses at 24 weeks as viable, because 50% of them survived and 78% of those survived without disability. Neonatal mortality and survival with disability further decreases with increasing gestational age.