bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonoperative management of bile leaks following liver transplantation
Authors: Johnston Thomas D , Gates Robert , Reddy K Sudhakar , Nickl Nicholas J , Ranjan Dinesh
Published: March 2003

The biliary anastomosis has been called ‘the Achilles heel’ of liver transplantation (Rabkin JM, Orloff SL, Reed MH. Transplantation 1998: 65 [2]: 193; Davidson BR, Rai R, Kurzawinski TR. Br J Surg 1999: 86 [4]: 447). Biliary complications after liver transplantation reportedly occur at an incidence of 20–30%, 10–15% as bile leaks. The management of bile leaks, especially early bile leaks, is controversial. In the present study, we report our experience with the management of bile leaks after liver transplantation.

 In this retrospective study, we reviewed 85 liver transplants over a 3‐yr period. In 79, the biliary anastomosis was choledochocholedochostomy (CDCD) over a small‐caliber T‐tube, while choledochojejunostomy (CDJ) was used in 7. Over a mean follow up period of 13.5 months (median 10 months), 10 patients (12%) experienced a clinically significant bile leak within the first 3 months after liver transplantation.

 The early leaks, occurring within 1 month of transplant, were successfully managed by observation (Davidson BR, Rai R, Kurzawinski TR. Br J Surg 1999: 86 [4]: 447) or endoscopic retrograde cholangiopancreatography (ERCP) and the placement of a biliary stent for a duration of 6–12 wk (Randall HB, Wachs ME, Somberg KA. Transplantation 1996: 61 [2]: 258). One of these resulted from accidental dislodgement of the T‐tube on postoperative day 1; one resulted from necrosis at the CDCD anastomosis and required CDJ; the remaining four resulted from leaks along the T‐tube track.

 One of the late leaks occurred following the planned removal of the T‐tube at 3 months after liver transplantation; the other two were leaks along the T‐tube track. All were successfully treated by ERCP and stent placement, though in one case, ERCP was initially unsuccessful because of the inability to advance a guidewire, necessitating a fluoroscopically aided guide wire placement during a mini laparotomy. ERCP was then successfully performed with the placement of a stent.Table 1Conclusions: Our experience indicates that most bile leaks after liver transplantation, including early leaks, can be successfully managed nonoperatively. Most will require intervention, but ERCP and stent placement are usually sufficient.

Time
Total (n)
Observed (n)
ERCP (n)
Surgery (n)
Follow‐up

Early (≤1 month after liver transplantation)
5
1
3
1
All doing well, median FU 12 months

Late (>1 month after liver transplantation)
5
1
4
1*
All doing well, median FU 5 months

*Managed by combined mini laparotomy and ECRP. FU, follow‐up.
Hospital charges following simultaneous kidney–pancreas transplantation: enteric drainage versus bladder drainage
Authors: Reddy K Sudhakar , Johnston Thomas D , Karounas Dennis , Ranjan Dinesh
Published: March 2003

Background. Enteric drainage (ED) is associated with reduced morbidity compared with bladder drainage (BD) after simultaneous kidney–pancreas transplantation (SKPT) and is becoming increasingly common (more than 50% of SKPTs done in the US in 1998 were performed with enteric drainage). Although several studies have reported the morbidity and graft survival of ED compared with BD previously, there are limited data available comparing the length of stay and hospital charges between these two drainage procedures.  Methods. Fourteen SKPTs were performed during the period January 1995–May 1998 using BD and 20 during June 1998–August 1999 using ED. Hospital charges analyzed included the following categories: pharmacy, inpatient room, laboratory, operating room, medical–surgical supply, radiology/nuclear medicine, and miscellaneous. Organ acquisition charges and professional fees were not included in this analysis.  Results. The mean hospital stay for patients with ED was 7.8±2.2 d (range 5–12 d; median 7.5 d) compared with 15.9±7 d (range 8–38 d; median 15 d) for patients with BD (p=0.002). The mean hospital charges during initial hospitalization for the ED group were $36 582±11 424 compared with $64 555±29 054 for the BD group (p=0.005). There was a significant decrease in the charges relating to pharmacy, inpatient room, laboratory, radiology/nuclear medicine, and miscellaneous category in the ED group compared with the BD group, while the charges relating to operating room and medical–surgical supply were no different between the two groups. One‐year actuarial kidney and pancreas graft survival rates were 83% and 93%, respectively, for the BD group and 90% and 80%, respectively, for the ED group (p=NS).  Conclusions. SKPT patients with ED had a 43% reduction in hospital charges and equivalent pancreas and kidney graft survival rates compared with SKPT patients with BD. A shorter hospital stay and a reduction in pharmacy, radiology/nuclear medicine, and laboratory charges contributed to the decreased hospital charges in SKPT patients with ED.
A comparison of prednisolone and methylprednisolone for renal transplantation
Authors: Hirano Toshihiko , Oka Kitaro , Takeuchi Hironori , Sakurai Etsuo , Kozaki Koichi , Matsuno Naoto , Kozaki Masami , Nagao Takeshi
Published: March 2003

A large difference in immunosuppressive potency between methylprednisolone and prednisolone has been suggested in vitro. However, the selection of the best glucocorticoid for renal transplantation has been seldom considered so far. Thus, the present study was undertaken to compare therapeutic efficacy between prednisolone and methylprednisolone in renal transplantation. We studied 42 renal transplant recipients who were operated on between 1990 and 1994. The patients were divided into two treatment groups: a methylprednisolone/cyclosporine group (n=19) and a prednisolone/cyclosporine group (n=23). Clinical outcome and drug side effects were compared retrospectively between the treatment groups 24–84 months after transplantation. The overall graft survival time in patients treated with methylprednisolone/cyclosporine was superior to that in patients treated with prednisolone/cyclosporine (p<0.05). Among the recipients from cadaver donors, 5/16 (31.3%) treated with prednisolone required nephrectomy, whereas none of the 10 patients treated with methylprednisolone received nephrectomy (p<0.01). An examination of the recipients from living related donors revealed that serum creatinine levels 24–36 months after operation were significantly lower in the methylprednisolone group (p<0.05). Cyclosporine trough levels and glucocorticoid side effects were similar between the treatment groups. The results raised the possibility that methylprednisolone is superior to prednisolone when combined with cyclosporine for maintenance immunosuppressive therapy in renal transplantation.
Low infectious complications in segmental living related small bowel transplantation in adults
Authors: Cicalese Luca , Sileri Pierpaolo , Asolati Massimo , Rastellini Cristiana , Abcarian Herand , Benedetti Enrico
Published: March 2003

Clinical small bowel transplantation (SBTx) has been associated with a high rate of infectious complications. Laparotomy, preservation injury, abnormal motility, lymphatic disruption, aberrant systemic venous drainage, rejection and antibiotic therapy could all be implicated in the etiology of these complications. In addition to the underlying disease, total parental nutrition could determine infections and liver impairment. Recently, standardized techniques for segmental living related SBTx (LR‐SBTx) have been developed. This technique allows reduction of some of these factors, thus resulting in a reduced incidence of infections. We report the infectious complications observed in 3 patients with short bowel syndrome treated with LR‐SBTx at our institution. A segment of 180–200 cm of ileum was transplanted with a neglectably short cold ischemia time (CIT). The donor bowel was decontaminated. Oral tacrolimus, prednisone and IV induction with ATG were used for immunosuppression. Blood, stool, urine, sputum and peritoneal fluids were collected and cultured as a routine surveillance. All recipients are alive with a current follow‐up time up to 21 months. No bacterial infections were observed during the post‐transplant period. One patient developed cytomegalovirus (CMV) enteritis 4 months after LR‐SBTx and was treated successfully with IV ganciclovir. In our limited experience, LR‐SBTx is associated with a low infection rate. This could be due to optimal graft decontamination, short CIT and to the reduced incidence of rejection and lower immunosuppression used in this immunologically well‐matched combination.
Organ procurement organization (OPO), best practices
Authors: Bollinger R. R. , Heinrichs D. R. , Seem D. L. , Rosendale J. D. , Johnson K. S. , Metzger R. A. ,   the UNOS Council for Organ Availability
Published: March 2003

There are currently 59 organ procurement organizations (OPOs) in the United States which serve their assigned geographic areas with variable productivity. Knowledge of organizational characteristics, programs and practices of more successful OPOs may be useful to increase the productivity of less successful OPOs. A preliminary survey of all OPO executive directors in the United States ascertained the most important beneficial and detrimental factors affecting their success. Site visits were then conducted at OPOs based on a selection process utilizing population size, geographic location, minority population, donors per million population and donors per thousand deaths among potential donors. All OPOs were categorized and the highest ranking OPOs in each of seven categories, based on 4 years of national data, were selected for the site visits. Regression analysis and correlation analysis using Pearson's product‐moment correlation were performed. The survey to identify the important factors was returned by 47 (77%) of 61 OPOs existent in 1999. The most important beneficial factors identified by responding OPOs were adequate staffing and experience, allocation of responsibilities, hospital development and leadership. The most important detrimental factors were inadequate staffing and experience, poor donor hospital/transplant center/OPO relationships and failure in the consent process. Site visits of the highest‐ranking OPOs demonstrated all had respected, experienced leadership focused on the donation process; efficient mechanisms for resolving allocation or transplant center conflicts; systems for monitoring activity and tracking outcomes; excellent communication between OPO and transplant centers; open internal communication at all levels of the OPO; immediate, on‐site response to vascular donor referrals; and volunteer support of public and/or professional education. Regression and correlation analysis demonstrated that as minority population increases, OPO performance declines (P<0.03). Moreover, independent OPOs were associated with poorer performance regardless of minority population (P<0.05). All of the successful OPOs visited had strong leadership, excellent donor hospital and transplant center relationships, well‐developed communication and innovative methods to deal with their minority populations. Application of these practices within all OPOs could significantly enhance organ donation.
A case of rapid progressive glomerulonephritis with IgA deposits after renal transplantation
Authors: Shimizu Tomokazu , Tanabe Kazunari , Tokumoto Tadahiko , Shimmura Hiroaki , Koga Shoji , Ishikawa Nobuo , Oshima Tadashi , Toma Hiroshi , Yamaguchi Yutaka
Published: March 2003

Shimizu T, Tanabe K, Tokumoto T, Shimmura H, Koga S, Ishikawa N, Oshima T, Toma H, Yamaguchi Y. A case of rapid progressive glomerulonephritis with IgA deposits after renal transplantation. Clin Transplantation 2001: 15 (Supplement 5): 11–15. ©Munksgaard, 2001

A 46‐yr‐old Japanese male who underwent a second cadaveric kidney transplantation on 31 October 1996 after suffering Type II diabetic mellitus for 25 yr was admitted to our institute on 23 January 1999, because of colicky abdominal pain and abdominal discomfort. Elevated levels of serum creatinine, severe proteinuria and microscopic haematuria were observed. The allograft biopsy specimen disclosed crescentic glomerulonephritis. Immunofluorescence showed granular deposits of mainly IgA and C3 along glomerular capillary walls and mesangial areas. Electron microscopy showed extensive subepithelial and mesangial electron dense deposits. Rapid and irreversible worsening of graft function led to resumption of haemodialysis on 31 May 1999. We speculated that this case was an atypical form of de novo Henoch–Schönlein purpura nephritis (HSPN) in transplanted kidney because of the histopathological findings of the allograft biopsy and clinical symptoms.
A case of tacrolimus nephrotoxicity appearing in a second renal transplantation patient
Authors: Oka Kazumasa , Moriyama Toshiki , Imai Enyu , Kyo Masahiro , Toki Kiyohide , Tanaka Toshiyuki , Hori Masatsugu , Kokado Yukito , Okuyama Akihiko , Takahara Shiro
Published: March 2003

Oka K, Moriyama T, Imai E, Kyo M, Toki K, Tanaka T, Hori M, Kokado Y, Okuyama A, Takahara S. A case of tacrolimus toxicity appearing in a second renal transplantation patient. Clin Transplantation 2001: 15 (Supplement 5): 30–34. ©Munksgaard, 2001

We experienced a case of a second renal trans‐ plantation patient. With the use of cyclosporin, he lost his first graft because of chronic rejection; with the use of tacrolimus, his second graft suffered from drug nephrotox‐ icity. On his second renal transplantation, his graft function deteriorated and required haemodialysis with the use of tacrolimus. Repeated biopsies did not reveal the typical characteristics of acute tacrolimus nephrotoxicity and acute rejection. His tacrolimus trough level was not high during the clinical course; however, by reducing tacrolimus dosage, his graft function eventually recovered to mild renal dys‐ function. This observation was helpful for clinical diagnosis of the functional toxicity of tacrolimus. The case is interest‐ ing in considering the functional toxicity of tacrolimus and the difference between tacrolimus and cyclosporin in terms of immunosuppressive and nephrotoxic actions.
Sequential anastomosis of accessory renal artery to inferior epigastric artery in the management of multiple arteries in live related renal transplantation: a critical appraisal
Authors: Kumar Anant , Gupta Raj Shekhar , Srivastava Aneesh , Bansal Pradeep
Published: March 2003

In live related renal transplant program, management of multiple renal arteries (MRA) is technically demanding and used to be considered a relative contraindication because of increased risk of vascular and urologic complications. We present a retrospective analysis of the outcome of grafts with MRA and suggest certain guidelines. Of the 680 live related kidney transplantations done, 53 allografts had MRA. Cases were grouped according to the reconstruction technique: group A, MRA reconstructed ex vivo into a single renal artery (n=27); group B, MRA with multiple anastomoses in vivo (n =13); group C, MRA with sequential revascularization using inferior epigastric artery (n=11). We compared serum creatinine, acute tubular necrosis, rejection rates and the rewarm ischemia time between the three groups. Overall patient survival and graft survival were excellent (100 and 96%). Mean serum creatinine at 1 yr did not differ significantly between the three groups. Rewarm ischemia time was significantly less in group C (p<0.01). Incidence of acute tubular necrosis and rejection episodes was also less in group C although the difference was statistically significant only between group C and group B. We conclude that allografts with MRA can be used successfully in a live related renal transplantation program. Bench reconstruction should be done whenever possible. For reconstruction of an accessory vessel, inferior epigastric artery with sequential revascularization is recommended.
Transforming growth factor‐β1 expression in early biopsy specimen predicts long‐term graft function following pediatric renal transplantation
Authors: Ishimura Takeshi , Fujisawa Masato , Isotani Shuji , Higuchi Akihiro , Iijima Kazumoto , Arakawa Soichi , Hohenfellner Katharina , Flanders Kathleen C , Yoshikawa Norishige , Kamidono Sadao
Published: March 2003

The main cause of late graft loss or declining long‐term graft function is chronic allograft nephropathy (CAN), characterized by progressive interstitial fibrosis. Transforming growth factor (TGF)‐β1 plays a key role in fibrogenesis. We immunohistochemically investigated whether the degree of TGF‐β1 expression in early biopsy specimens routinely obtained from stable allografts at 100 d could predict fibrosis and graft dysfunction in the late phase. Patients were children with grafts from related donors. We immunohistochemically determined intracellular and extracellular expression of TGF‐β1 in the graft using LC antibody (LC) for intracellular TGF‐β1 and CC antibody (CC) for extracellular TGF‐β1. The change in creatinine clearance between 100 d and 3 yr after transplantation (ΔCcr) was used as an index of long‐term graft function. We also used image analysis to calculate the relative area involved by interstitial fibrosis in the trichrome‐stained section of graft biopsy specimens at 100 d and 3 yr, designating the change as ΔFI. ΔCcr was −4.2±9.4 mL/min in subjects with minimal early immunoreactivity for CC and −20.5±15.9 mL/min in subjects with strong reactivity (p<0.05). ΔCcr was −14.5±18.6 mL/min in subjects with minimal early immunoreactivity for LC and −11.7±12.8 mL/min in those with strong reactivity. ΔFI in subjects with minimal CC reactivity (1.28±4.11%) tended to be lower than that in subjects with strong reactivity (8.45±15.47%). Neither fibrosis at 100 d nor ΔFI differed between subjects with minimal and strong LC reactivity. Thus, strong extracellular TGF‐β1 expression in grafts at 100 d after transplantation is associated with a long‐term decline in graft function and tends to be associated with increased graft fibrosis at 3 yr.
Emotional issues after kidney transplantation: a prospective psychotherapeutic study
Authors: Baines Lyndsay S , Joseph John T , Jindal Rahul M
Published: March 2003

Abstract: Background:  Negative emotional states are the single most influential factor in determining quality of life after a successful kidney transplant. We designed a prospective study using psychotherapeutic principles to understand and intervene in emotional issues in adult recipients of first cadaver kidney transplants.

Methods:  Forty‐nine recipients of first cadaver kidney transplants were subjected to 12 sessions (at weekly intervals) of psychotherapy within 3 months of receiving their transplant. The Beck Depression Inventory (BDI) was utilized as a measure of change in emotional state, pretherapy, at 3, 6, 9 and 12 months. A higher score on BDI was suggestive of psychological dysfunction. In the first instance, data was analysed within a quantitative framework, by virtue of the BDI. In the second instance, data was considered in terms of recurring themes described by patients during psychotherapy and was analysed qualitatively. In the third instance, both qualitative and quantitative data was considered in terms of individual patient's ability to achieve some feeling of having implemented some social, relational and vocational equilibrium into their everyday life. Recipients of live kidneys, paediatric transplants and patients who received more than one transplant were excluded, as emotional issues are different in this cohort of patients. All patients have completed 1 yr of follow up. None of the patients were on antidepressant medication before or after therapy.

Results:  This is an ongoing study in which we are comparing individual vs. group therapy vs. controls (who receive no therapy). The total number of patients recruited will be 120 and the final report will be available in 2003–04. The results reported in this paper form the 49 patients in the individual arm of the study. All the patients in our study happened to be white people. There was significant improvement in the BDI scores following therapy. The mean score was 26.3 ± 7.9 before and 20.5 ± 8.8 after therapy (p = 0.001); the lowering of the scores remained sustained at 12 months. Multivariate analysis of age, gender, employment status, duration of dialysis (if in dialysis for more than 3 yrs) and psychotherapy given before transplantation did not affect the results of our study. For the qualitative aspect of the study, we grouped the emotional problems as expressed by the patients into three recurring themes (i) fear of rejection, (ii) feelings of paradoxical loss post‐transplant despite having received a successful transplant and (iii) the psychological integration of the newly acquired kidney.

Conclusions:  Psychotherapeutic intervention was an effective means of addressing emotional problems in recipients of kidney transplants. The recurring themes as identified above provided a baseline for psychotherapeutic exploration and resolution of these issues. Successful resolution of these issues was associated with lower BDI scores and the redefinition of normality in daily living post‐transplant.
Technique of bile duct reconstruction and management of biliary complications in right lobe living donor liver transplantation
Authors: Settmacher U , Steinmüller TH , Schmidt SC , Heise M , Pascher A , Theruvath T , Hintze R , Neuhaus P
Published: March 2003

Abstract:  From December 1999 to January 2002, 50 right lobe living donor liver transplantations were performed. The donor operations included an intraoperative cholangiography to elicit variations in bile duct anatomy. The biliary reconstruction was done whenever possible as an end‐to‐end microanastomosis of the donor right hepatic duct with the recipient's bile duct. As a result of the early segmental branching of the donor biliary tree, two segment bile ducts had to be anastomosed in 20 patients and three segment bile ducts in three patients. In 12 patients, a Roux‐en‐Y hepaticojejunostomy was performed. All anastomoses were drained externally. We observed two leakages at the resection surface which could be treated successfully by an external drainage. Six leaks occurred at the site of end‐to‐end biliary anastomoses. Twice the problem could be conservatively solved placing a stent percutaneously. In two patients a hepaticojejunostomy was performed after a bile duct necrosis. In two patients with an anastomotic leak, occurring 3 d, respectively, 3 month after the original transplantation, the bile duct could be directly reconstructed over a T‐tube. Two anastomotic stenoses were observed, one in combination with a leak treated by percutaneous stent implantation and the second, 3 month after transplantation which was treated surgically. Biliary reconstruction after living donor liver transplantation requires microsurgical techniques and can be performed as a direct end‐to‐end anastomosis in most cases. Biliary complications were treated by percutaneous drainage or surgical revision in all cases.
Renal allograft arteriovenous fistula and large pseudoaneurysm
Authors: Nakatani Tatsuya , Uchida Junji , Han Young S , Iwai Tomoaki , Nakamura Kenji , Kawashima Hidenori , Sugimura Kazunobu
Published: March 2003

Abstract:  The patient was a 51‐year‐old female. Post‐biopsy arteriovenous fistula (AVF) and pseudoaneurysm in a renal allograft were diagnosed 5 yr and 4 months after she received a renal transplantation. Four years after the diagnosis, interventional treatment for the AVF and pseudoaneurysm was performed because of a high risk of pseudoaneurysm rupture. Although the longitudinal diameter of the pseudoaneurysm was more than 5 cm, this AVF and pseudoaneurysm were treated successfully by a percutaneous transluminal embolization, and renal function has remained stable after embolization. A selective interventional procedure proved effective for the large pseudoaneurysm in the renal allograft. Therefore, when a transcutaneous needle biopsy of the renal allograft is performed, although there are no apparent symptoms or signs of vascular complications during the clinical course, periodical examinations such as echo‐Doppler imaging should be made on the allograft.
Inositol as an add‐on treatment for bipolar depression
Authors: Chengappa Kn Roy , Levine Joseph , Gershon Samuel , Mallinger Alan G , Hardan Antonio , Vagnucci Anthony , Pollock Bruce , Luther James , Buttenfield Joan , Verfaille Steve , Kupfer David J
Published: March 2003

Objective:

Inositol is a constituent of the intracellular phosphatidyl inositol (PI) second messenger system, which is linked to various neurotransmitter receptors. Inositol crosses the blood–brain barrier in pharmacological doses, and has shown efficacy in a small double‐blind study of unipolar depression. This pilot study evaluated its potential efficacy and safety in bipolar depression.   Methods: Twenty‐four consenting adult men and women with DSM‐IV bipolar depression (bipolar I=21; bipolar II=3) were randomly assigned to receive either 12 g of inositol or
d‐glucose as placebo for 6 weeks. Efficacy and safety ratings were done weekly. Thymoleptic medications (lithium, valproate, carbamazepine) in stable doses and at therapeutic levels at study entry were continued unchanged.   Results: Two subjects receiving placebo dropped out early due to worsening or non‐adherence to the protocol. Among the 22 subjects who completed the trial, six (50%) of the inositol‐treated subjects responded with a 50% or greater decrease in the baseline Hamilton Depression Rating Scale (HAM‐D) score and a Clinical Global Improvement (CGI) scale score change of ‘much’ or ‘very much’ improved, as compared to three (30%) subjects assigned to placebo, a statistically non‐significant difference. On the Montgomery–Asberg Depression Rating Scale (MADRS), eight (67%) of twelve inositol‐treated subjects had a 50% or greater decrease in the baseline MADRS scores compared to four (33%) of twelve subjects assigned to placebo (p=0.10). Inositol was well tolerated with minimal side effects, and thymoleptic blood levels were unaltered.   Conclusions: These pilot data suggest a controlled study with an adequate sample size, and the appropriate rating scale may demonstrate efficacy for inositol in bipolar depression. The tolerability and the ‘natural substance’ aspect of inositol may be particularly appealing to subjects with bipolar depression.
Relationship of childhood physical and sexual abuse to adult bipolar disorder
Authors: Hyun Mina , Friedman Seth D , Dunner David L
Published: March 2003

Objectives:

To characterize whether adult depressives with either bipolar or unipolar disorder differ in the prevalence of childhood sexual or physical abuse.   Method: The investigators reviewed data from patients who were evaluated over a 2‐year period by a semi‐structured clinical interview. In total, 333 cases with a bipolar or unipolar diagnosis were included in the present study.   Results: A childhood history of abuse, in particular sexual abuse, was significantly more frequent in bipolar subjects compared with unipolar subjects. Consistent with previous studies, women reported higher rates of sexual abuse than men, although no interaction by diagnosis was shown. Sexual abuse incidence in male samples was markedly dissimilar, with male bipolar subjects demonstrating a significantly increased rate of sexual abuse and combined sexual and physical abuse compared with unipolar male subjects.   Conclusion: The increased incidence of sexual abuse in women supports growing evidence of gender differences in sexual abuse among adult depressives. In contrast to literature reports, the finding that male bipolar patients have significantly increased rates of sexual abuse histories suggests differences in psychiatric depressive subgroups. This result may reflect the particular characteristics of our cohort (treatment resistant, privately insured, and educated). Further work will aid in characterizing sexual abuse prevalence in other male bipolar samples.
Neuroimaging in bipolar disorder
Authors: Strakowski Stephen M , DelBello Melissa P , Adler Caleb , Cecil Kim M , Sax Kenji W
Published: March 2003

Objective:

The authors reviewed neuroimaging studies of bipolar disorder in order to evaluate how this literature contributes to the current understanding of the neurophysiology of the illness.   Method: Papers were reviewed as identified, using the NIMH PubMed literature search systems that reported results of neuroimaging studies involving a minimum of five bipolar disorder patients compared with healthy comparison subjects.   Results: Structural neuroimaging studies report mixed results for lateral and third ventriculomegaly. Recent studies suggest subcortical structural abnormalities in the striatum and amygdala, as well as the prefrontal cortex. Proton spectroscopic studies suggest that abnormalities in choline metabolism exist in bipolar disorder, particularly in the basal ganglia. Additionally, phosphorous MRS suggests that there may be abnormalities in frontal phospholipid metabolism in bipolar disorder. Functional studies have identified affective state‐related changes in cerebral glucose metabolism and blood flow, particularly in the prefrontal cortex during depression, but no clear abnormalities specific to bipolar disorder have been consistently observed.   Conclusions: The current literature examining the neurophysiology of bipolar disorder using neuroimaging is limited. Nonetheless, abnormalities in specific frontal‐subcortical brain circuits seem likely. Additional targeted studies are needed to capitalize on this burgeoning technology to advance our understanding of the neurophysiology of bipolar disorder.
Does olanzapine have antidepressant properties? A retrospective preliminary study
Authors: Nassir Ghaemi S , Cherry Erica L , Katzow Jacob A , Goodwin Frederick K
Published: March 2003

Objective:

Mood‐stabilizing agents are ideally conceptualized as possessing antimanic and antidepressant properties. While research on olanzapine's antimanic effects is growing, data on its possible antidepressant properties are limited. We sought to determine if olanzapine is effective in the add‐on treatment of major affective disorders, particularly depressive symptoms, in a naturalistic setting.   Methods: All charts of patients meeting DSM‐IV criteria for bipolar disorder or unipolar major depressive disorder treated with olanzapine in a private psychiatric practice were reviewed and clinical response was assessed retrospectively using the Clinical Global Impression Scale for Improvement (CGI‐I).   Results: Olanzapine was moderately effective in 6/10 (60%) patients. Side‐effects were present in 8/10 (80%), most commonly weight gain.   Conclusions: Olanzapine appears to be moderately effective in open add‐on treatment in patients with mainly depressive symptoms. Accumulating evidence suggests that olanzapine, and atypical antipsychotics in general, possess mild to moderate adjunctive antidepressant properties.
Illness characteristics and their association with prescription patterns for bipolar I disorder
Authors: Levine Joseph , Chengappa Kn Roy , Brar Jaspreet S , Gershon Samuel , Kupfer David J
Published: March 2003

Introduction:
The present study explores the relationships among psychotropic medications, illness‐related parameters, patient demography, suicidality, and levels of functioning in a voluntary bipolar case registry.   Methods: Four hundred and fifty‐seven subjects with bipolar I disorder were selected from a voluntary registry for subjects with bipolar illness. Demographic characteristics, psychotropic medications, age at onset of illness, duration of illness, number of hospitalizations, the ability to live independently, employment and driving status as well as the history of suicidal attempts were obtained through a structured phone interview.   Results: Subjects treated with antidepressants had a shorter duration of illness, while patients treated with antipsychotic drugs had an earlier onset of illness. The number of hospitalizations for mania was fewer among patients taking a combination of lithium and carbamazepine as compared to patients not receiving them, while subjects taking neuroleptics had more hospitalizations as compared to subjects not receiving them. The number of psychotropic agents prescribed correlated positively with the number of hospitalizations for depressive episodes. Curiously, no correlations were found between the types of psychotropic agents prescribed and the levels of functioning or a history of suicidal attempts. Interestingly, our results suggest that more than half of the subjects were unable to live independently or to work due to their illness. Also, more than 50% of the subjects had at least one suicidal attempt, the majority occurred during depressive episodes.   Conclusions: Our results suggest that subjects with bipolar I disorder have high rate of suicidal attempts and may have serious functional impairments.
Electrophysiological and cognitive function in young euthymic patients with bipolar affective disorder
Authors: El‐Badri Selim M , Ashton C Heather , Moore P Brian , Marsh V Richard , Ferrier I Nicol
Published: March 2003

Objectives:
EEG abnormalities and neurocognitive deficits have been reported in patients with bipolar affective disorder. The aim of this study was to ascertain whether brain function remains impaired in young bipolar patients who have become euthymic in response to treatment.   Methods: Brain function was assessed by quantitative electroencephalographic (EEG) power‐spectral mapping and by a battery of neuropsychological tests. The subjects were 29 euthymic bipolar patients aged 18–40 years and 26 healthy volunteers of similar age, IQ and socioeconomic status.   Results: Grand means of spectral power of the resting EEG showed significantly (from p<0.01 to p<0.0001) greater power in all wave bands (delta, theta, alpha and beta) in patients compared with controls. The most marked increases were in right temporal theta and left occipital beta power (with eyes open) encompassing brain areas concerned in visuospatial processing. Neurocognitive performance was significantly impaired in the patients compared with controls in a range of visuospatial tasks.   Conclusions: The findings show significant disturbance of EEG activity and deficits in visuospatial processing in young bipolar patients despite clinical euthymia. The abnormalities were not related to age of onset or duration of illness and do not appear to be attributable to medication. The cognitive impairments were associated with the number of previous affective episodes.
The neuropsychology and neuroanatomy of bipolar affective disorder: a critical review
Authors: Bearden Carrie E , Hoffman Kathleen M , Cannon Tyrone D
Published: March 2003

Objectives:
To present a comprehensive review of the existing neuropsychological and neuroimaging literature on bipolar affective disorder. This review critically evaluates two common conceptions regarding the neuropsychology of bipolar disorder: 1) that, in contrast to schizophrenia, bipolar affective disorder is not associated with general cognitive impairment independent of illness episodes, and 2) relative right hemisphere (RH) dysfunction is implicated in bipolar illness patients, supported by reports of relatively greater impairment in visuospatial functioning, lateralization abnormalities, and mania secondary to RH lesions.  Methods: The major computerized databases (Medline and PSYCInfo) were consulted in order to conduct a comprehensive, integrated review of the literature on the neuropsychology and neuroanatomy of bipolar disorder. Articles meeting specified criteria were included in this review.  Results: In a critical evaluation of the above notions, this paper determines that: 1) while there is little evidence for selective RH dysfunction, significant cognitive impairment may be present in bipolar illness, particularly in a subgroup of chronic, elderly or multiple‐episode patients, suggesting a possible toxic disease process, and 2) the underlying functional correlate of these cognitive deficits may be white matter lesions (‘signal hyperintensities’) in the frontal lobes and basal ganglia, regions critical for executive function, attention, speeded information processing, learning and memory, and affect regulation. While this hypothesized neural correlate of cognitive impairment in bipolar disorder is speculative, preliminary functional neuroimaging evidence supports the notion of frontal and subcortical hypometabolism in bipolar illness.  Conclusions: The etiology of the structural brain abnormalities commonly seen in bipolar illness, and their corresponding functional deficits, remains unknown. It is possible that neurodevelopmental anomalies may play a role, and it remains to be determined whether there is also some pathophysiological progression that occurs with repeated illness episodes. More research is needed on first‐episode patients, relatives of bipolar probands, and within prospective longitudinal paradigms in order to isolate disease‐specific impairments and genetic markers of neurocognitive function in bipolar disorder.
Psychiatric diagnoses in the context of genetic studies of bipolar disorder
Authors: Duffy Anne , Grof Paul
Published: March 2003

Precise definition of the phenotype is an issue of critical importance for the future success of genetic studies of bipolar disorders. So far, an uncertain phenotypic spectrum and genetic heterogeneity are realities that have hampered progress in genetic studies. While recognition of a broader spectrum of related illnesses is important for some applications, for genetic studies a narrow spectrum of illness closely tied to the genotype is paramount. This paper highlights current dilemmas and trends associated with phenotype specification and traces historical approaches. Finally, we explore a number of strategic directions in the diagnostic approach to bipolar disorders that may better serve genetic studies.
Population isolates: their special value for locating genes for bipolar disorder
Authors: Escamilla Michael A
Published: March 2003

Objectives:
Population isolates offer several advantages for those hoping to identify predisposition genes for bipolar disorder (BP). In this review article, the rationale for performing gene mapping studies in this type of population and the results of genetic mapping studies performed to date in population isolates are presented.   Methods: This article begins with a brief review of the concepts involved in mapping genes for BP. The concept of populations that show some degree of historical isolation and their special utility for certain types of gene mapping is presented. Methods of statistical analysis particularly relevant for gene mapping of complex diseases like BP are presented. Finally, several BP gene studies conducted to date in several population isolates are reviewed.   Results: Genetic mapping studies of BP have occurred thus far in several isolates or sub‐isolates, including the Amish population, Costa Ricans, Finnish, and Canadians (in Quebec), and significant linkage scores have been identified in the latter three isolates.   Conclusions: Possible greater homogeneity and greater consistency of diagnosis are factors that have been cited in several studies of BP done in isolates to date. Another special advantage of working in certain types of population isolate is their appropriateness for using certain types of association or linkage disequilibrium‐based approaches at both the genome screening and fine mapping stages. These tests include mapping by linkage disequilibrium analyses, an approach that allows mapping to occur at the population, rather than the pedigree, level.
Evaluation of neuroprotection by lithium and valproic acid against ouabain‐induced cell damage
Authors: Hennion JP , El‐Masri M Adnan , Huff Mary O , El‐Mallakh Rif S
Published: March 2003

Background:
The pathophysiology of manic‐depression may be associated with dysregulation of ion homeostasis. Ouabain is a potent inhibitor of the sodium–potassium adenosine triphosphatase and has been purported to mimic abnormalities seen in acute mania. As manic episodes are believed to be neurotoxic and mood stabilizers have recently been implicated as neuroprotectants, it is of interest to determine if lithium and valproic acid antagonize ouabain‐induced neurotoxicity.

Methods:
 Human neuroblastoma SH‐SY5Y cells were differentiated for 12 days then pretreated with lithium or valproic acid for 24 h and then challenged with a 10 μM ouabain insult. Cellular damage was assessed with lactate dehydrogenase (LDH) release, and apoptotic potential of ouabain was evaluated with DNA fragmentation.

Results:
 Ouabain significantly increased LDH release after 72 h of treatment. Lithium pretreatment at 1 mM diminished ouabain‐induced LDH release. Valproic acid alone at 100 and 1000 μg/mL significantly increased LDH release from the cells. Furthermore, it significantly potentiated ouabain‐induced LDH release. DNA fragmentation suggests that ouabain induces apoptosis.

Conclusions:
 Lithium at the therapeutic level of 1 mM limits the extent of cellular damage caused by 10 μM ouabain in SH‐SY5Y cells as measured by LDH release. Valproic acid alone at the therapeutic concentration of 100 μg/mL induces LDH release and does not prevent ouabain‐induced LDH release.
Olanzapine in diverse syndromal and subsyndromal exacerbations of bipolar disorders
Authors: Janenawasin Suttiporn , Wang Po W , Lembke Anna , Schumacher Matthew , Das Bibi , Santosa Claudia M , Mongkolcheep Jenny , Ketter Terence A
Published: March 2003

Objective:  To evaluate effects of olanzapine in diverse exacerbations of bipolar disorders.

Methods:  Twenty‐five evaluable bipolar disorder [14 bipolar I (BPI), 10 bipolar II (BPII) and one bipolar disorder not otherwise specified (BP NOS)] outpatients received open olanzapine (15 adjunctive, 10 monotherapy). Thirteen had elevated (11 syndromal, two subsyndromal) and 12 depressed (four syndromal, eight subsyndromal) mood symptoms of at least mild severity, with Clinical Global Impression‐Severity (CGI‐S) scores of at least 3. Only one had psychotic symptoms.

Results:  With open olanzapine (15 adjunctive, 10 monotherapy), overall symptom severity (CGI‐S) as well as mood elevation (Young Mania Rating Scale), depression (Hamilton and Montgomery‐Asberg Depression Rating Scales), and anxiety (Hamilton Anxiety Rating Scale), rapidly decreased (significantly by days 2–3). Patients with the greatest baseline severity (CGI‐S) had the greatest improvement. Fifteen of 25 (60%) patients responded. Time to consistent response was bimodal, with five early (by 0.5 ± 0.3 weeks) and 10 late (by 7.0 ± 1.9 weeks) responders. Early compared with late responders had 51% lower final olanzapine doses. Olanzapine was generally well tolerated, with sedation and weight gain the most common adverse effects.

Conclusions:  Olanzapine was effective in diverse exacerbations of bipolar disorders. The bimodal distribution of time to response and different final doses are consistent with differential mechanisms mediating early compared with late responses. Controlled studies are warranted to further explore these preliminary observations.
Ziprasidone‐associated mania: a case series and review of the mechanism
Authors: Baldassano CF , Ballas C , Datto SM , Kim D , Littman L , O'Reardon J , Rynn MA
Published: March 2003

Atypical antipsychotics are now commonly used in the treatment of bipolar disorder, as they have been shown to have effects on mania as well as psychosis. Shortly after the introduction of atypical antipsychotics, several cases of associated hypomania and mania were reported. Ziprasidone is an atypical antipsychotic recently approved by the Food and Drug Administration for the treatment of psychosis. Although ziprasidone has also been shown to be effective in treating mania, it may be associated with the induction of mania or hypomania. We report four cases of mania associated with initiation of ziprasidone, which, to our knowledge, are the first reported for this drug in bipolar patients. As ziprasidone has substantial serotonergic and noradrenergic action, we hypothesize, it may more likely induce mania than other atypical antipsychotics. We advocate future studies to evaluate ziprasidone's efficacy in treating bipolar disorder and caution clinicians that induction of mania or hypomania may be possible with this agent.
Transcranial direct current stimulation: a new treatment for depression?
Authors: Nitsche MA
Published: March 2003

Nitsche MA. Transcranial direct current stimulation: a new treatment for depression?  Bipolar Disord 2002: 4(Suppl. 1): 98–99. © Blackwell Munksgaard, 2002
Is pelvic pain in pregnancy a welfare complaint?
Authors: BJÖRKLUND KENNETH , BERGSTRÖM STAFFAN
Published: March 2003

Background. Pelvic pain in pregnancy has been suggested to be more common in Scandinavia than in the rest of the world, to be culturally specific for the region and to reflect a change in attitude among pregnant women. Little is known of the prevalence of pelvic pain in pregnancy in low‐income countries.

Objective. To explore whether perceived pelvic pain among pregnant women differs between affluent and poor societies.

Subjects and methods. Four observational studies, comprising a total of 752 women, were carried out in circumstances ranging from wealth to poverty, focusing on the reported prevalence, location and degree of pelvic pain in pregnancy. In Uppsala, Sweden, and in Rufiji, Tanzania, the women were interviewed in late pregnancy. In Jakobstad, Finland, and in Zanzibar Town, Zanzibar, the women were approached after delivery before discharge.

Results. The reported prevalence of pelvic pain in pregnancy was 49% in Uppsala and 66% in Rufiji, 77% in Jakobstad and 81% in Zanzibar, with an overall similarity of location and degree of pain.

Conclusion. No geographical differences were found in perceived pelvic pain among pregnant women, irrespective of the socio‐economy of the countries.
DNA strand breaks in human spermatozoa: Correlation with fertilization in vitro in oligozoospermic men and in men with unexplained infertility
Authors: HØST ERIK , LINDENBERG SVEND , SMIDT‐JENSEN STEEN
Published: March 2003

Background. The purpose of this study was to examine the correlation between DNA strand breaks in human spermatozoa and semen quality, fertilization rate and IVF outcome.

Methods. A total of 50 men suffering from unexplained infertility and 50 men with oligozoospermia undergoing IVF treatment entered a prospective study. Sperm samples were assessed according to the WHO manual and for the presence of DNA strand breaks in spermatozoa. The study was blinded for the technician involved in assessment of DNA strand breaks. IVF was carried out according to a long down regulation protocol using GnRH, FSH and hCG. The ova were inseminated with 200,000 spermatozoa/ml. Embryos were transferred on day 2 after fertilization with a maximum of three embryos.

Results. This study demonstrates a negative correlation between the proportion of spermatozoa having DNA strand breaks and the proportion of oocytes fertilized after IVF.

Conclusion. The number of human spermatozoa with DNA strand breaks is a good predictor for fertilization rate in couples suffering from unexplained infertility and undergoing IVF treatment.