bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving the therapeutic monitoring of cyclosporin A
Authors: Warrens AN , Waters JB , Salama AD , Lechler RI
Published: March 2003

The narrow therapeutic window of cyclosporin A (CsA) and the variable pharmacokinetics of the traditional preparation, CsA‐SIM (Sandimmune™), have made it difficult to establish its optimal use. The introduction of a microemulsion preparation, CsA‐ME (Neoral™), with less variable pharmacokinetics, has made it possible to attempt to define its use more closely. One hundred and one renal allograft recipients were converted from CsA‐SIM to CsA‐ME. Absorption was monitored using a standard pharmacokinetic ‘profile’ measuring ‘whole blood’ CsA levels at several time points following drug administration. Areas under the resulting time‐versus‐CsA concentration curve (AUC) were calculated. Surprisingly, many patients showed very little fluctuation in ‘whole blood’ levels after administration of the conventional preparation: 31% had a difference between trough (t0) and maximal levels of <100 μg/L. On microemulsion cyclosporin, there was much better correlation between AUC and several parameters incorporating elements of trough and peak values. The best correlation was with t0+(t1/4), where t1 represents the concentration at 1 h following administration, (r2=0.779 for microemulsion cyclosporin). The use of this parameter is a practical possibility in an out‐patient setting. The very common, but under‐recognised, pattern of almost flat absorption profiles in patients on conventional CsA suggests that the use of CsA in numerous clinical contexts should be reviewed, since CsA immunosuppression may previously have been inadequately monitored.
The poor accuracy of indirect measurements of cadaveric donor kidney weights
Authors: Bunke M , Marx Ma , Abul‐Ezz S , Almquist G , Barone G , Ketel B
Published: March 2003

Reports that examined the issue of whether transplantation of inadequate nephron mass may be a risk factor for long‐term allograft failure yielded conflicting results. One of the more accurate methods of estimating glomerular mass is kidney weight. Most of the clinical studies used body surface area (BSA) or kidney length as estimates of kidney weight. To test the hypothesis that indirect measures of kidney weight are accurate estimates of kidney weight, we compared the kidney weight of 41 consecutive cadaveric kidneys to donor BSA, dimensions measured with calipers at the time of transplantation, and dimensions supplied by the Organ Procurement Agency (OPA). Linear regression analysis was used with kidney weight as the dependent variable and BSA, kidney length, or kidney volume as the independent variable. Kidney length measured with calipers was also compared to kidney length supplied by the OPA. Kidney weight had the best correlation with kidney volume and kidney length determined by caliper measurements (r=0.640 and 0.646, respectively). The regression analysis showed that the correlation of kidney weight with BSA was 0.487. The correlation of OPA‐provided kidney length with kidney weights was poor (r=0.410). The linear regression of caliper‐measured kidney length versus OPA length yielded a slope of 0.360, instead of an ideal slope of 1.The assumption has been made that kidney weight or a surrogate of kidney weight has an excellent correlation with nephron mass. Some of the variability in studies that attempted to examine the effect of transplanted nephron mass on allograft outcome may be due to inaccurate estimates used for kidney weight. Our data suggest that surrogate measurements of kidney weight may not be accurate. We recommend that measured kidney weight should be used in studies examining the effect of donor renal mass on allograft outcomes.
Interleukin‐10 in Epstein–Barr virus‐associated post‐transplant lymphomas
Authors: Garnier Jeanne‐Luce , Blanc‐Brunat Nelly , Vivier Geneviève , Rousset Françoise , Touraine Jean‐Louis
Published: March 2003

We used enzyme‐linked immunosorbent assays (ELISA) to investigate the presence of interleukin‐10 (IL‐10) in the serum of patients developing post‐transplant lymphomas. Serum IL‐10 was detected in 14 out of 19 cases with a lymphoma or Hodgkin's disease, with higher values being observed in patients who had developed a lymphoma within the first few months post‐transplantation, and who had an aggressive form of the disease. Eleven out of the 14 patients in whom IL‐10 was detected had Epstein–Barr virus‐positive tumors. And 11 out of 14 patients died of lymphomas. In most of the patients who had detectable IL‐10 at the time of diagnosis of the lymphoma, the IL‐10 had not been present previously, but it was found in the serum of 7 out of 9 dialysis patients, and in 8 out of 17 stable transplant patients. We conclude that IL‐10 plays a role in the development of the more severe forms of post‐transplant lymphomas, and may be secreted by tumor cells. However, data from patients with chronic renal failure or patients undergoing immunosuppressive therapy must be treated with caution.
Adhesion molecules in patients after lung transplantation
Authors: Bewig B , Tiroke A , Böttcher H , Padel K , Hirt S , Haverich A , Cremer J
Published: March 2003

Leukocyte adhesion molecules, such as intercellular adhesion molecule (ICAM)‐1 and its ligands, are involved in inflammatory processes of the lung. For ICAM‐1, differential expression during different kinds of complications after transplantation has been proposed.

We analyzed the role of ICAM‐1, CD18, CD11a, CD11b, and CD11c during episodes of rejection or infection in patients after lung transplantation and compared the results to episodes without apparent complication. A total of 98 bronchoalveolar lavage (BAL) samples and 90 serum samples were analyzed.

ICAM‐1, CD18, CD11a, CD11b, and CD11c expressions were detected immunocytochemically on alveolar macrophages. Soluble ICAM‐1 was quantified in serum and BAL. In the control group, 49.8±18% of macrophages stained positive for CD11b. During rejection, the mean of cells showing CD11b on the surface was significantly higher (64.6±11.4%), with no difference compared to episodes of infection (59.7±22.7). All other epitopes were not expressed differently with regard to a normal clinical course or episodes of infection and rejections.

In summary, assessment of ICAM‐1 and corresponding ligands did not allow for a reliable discrimination between episodes of rejection or infection in lung transplantation.
Low‐dose dopamine after kidney transplantation: assessment by Doppler ultrasound
Authors: Spicer St , Gruenewald S , O'connell Pj , Chapman Jr , Nankivell Bj
Published: March 2003

Low‐dose dopamine (LDD) is commonly used after kidney transplantation as a renoprotective agent, although the benefits of dopamine (DA) in this setting are controversial. LDD increases renal blood flow, decreases resistive index (RI) and causes diuresis in normal kidneys. We hypothesised that the vasculature of a denervated renal transplant may not respond to DA in the same way as healthy native kidneys. In a prospective, controlled study, renal blood flow velocity and vascular resistance were measured by Doppler ultrasound in recent kidney transplants (n=20) over a range of DA doses (0–5 μg/kg/min). Main renal artery velocity was lower in kidneys with acute renal dysfunction than in those with normal function (0.60±0.31 vs. 0.81±0.24, respectively, p<0.05). There was no demonstrable haemodynamic effect of LDD on either RI or main renal artery velocity as measured by Doppler ultrasound. Interestingly, the only significant correlation with mean RI was trough cyclosporin A level (r=0.57, p<0.001). Technical or timing factors cannot be used to explain the absence of DA effect, with equivalent doses capable of producing vasodilatation and reduced RI in studies of normal kidneys. In summary, these findings contrast the DA response of healthy native kidneys and may explain studies showing no clinical benefit of LDD in the early post‐transplant period. These data suggest an insensitivity of recently implanted kidneys to the vasodilatory effects of LDD, that other factors such as cyclosporin A vasoconstriction may also be important, and question the rationale for routine LDD after kidney transplantation.
Arteriolopathy in non‐episode biopsies of renal transplant allograft
Authors: Toki Kiyohide , Kyo Masahiro , Takahara Shiro , Morozumi Kunio , Ichimaru Naotsugu , Tanaka Toshiyuki , Wang Jing‐Ding , Permpongkosol Sompol , Oka Kazumasa , Imai Enyu , Miyamoto Makoto , Kyakuno Miyaji , Nakamura Takayuki , Kojima Yasuyuki , Kokado Yukito , Okuyama Akihiko
Published: March 2003

Purpose. We have been performing protocol biopsies since 1995 to predict the outcome of renal allograft. However, histopathological findings in renal allograft with stable function remain unclear. For this reason, we performed non‐episode biopsy on long‐surviving renal allograft and investigated the histopathological changes. Among the several diseases seen in non‐episode biopsies, arteriolopathy, such as drug‐induced nephropathy, is one of the most frequent diseases. However, it is unrelated to the dosage and the concentration of cyclosporine or tacrolimus. Consequently, we evaluated the clinicopathological findings of arteriolopathy in this study in order to clarify whether cyclosporine (CsA) or tacrolimus (FK506) is responsible for these findings.  Materials and methods. We defined non‐episode biopsy as a case with a serum creatinine level less than 2.0 mg/dL and containing less than 500 mg/dL of urinary protein. Final results showed that 71 cases were identified as non‐episode biopsy. We then evaluated the histopathological findings and the clinical characteristics of these cases.  Results. Thirty‐two of the 71 non‐episode biopsy specimens showed findings of arteriolopathy. The frequency and the severity of arteriolopathy are not concerned with dosage and concentration of CsA or FK506. The arteriolopathy seen in non‐episode biopsy was related to the time of the biopsy and the kidney age. Arteriolopathy in non‐episode biopsy also had a relationship with hypertension, suggesting that it is important to strictly control blood pressure for graft survival.
Influence of anti‐rejection therapy on the timing of cytomegalovirus disease and other infections in renal transplant recipients
Authors: Jamil Bilal , Nicholls Kathy M , Becker Gavin J , Walker Rowan G
Published: March 2003

Infections are an important cause of mortality and morbidity in renal transplant recipients. To study the impact of anti‐rejection therapy on the timing of infections, the records of 599 consecutive renal transplants, performed prior to 31 December 1996 at the Royal Melbourne Hospital, were reviewed. Patients were grouped according to acute rejection (AR) episode and treatment during the first 6 months after transplantation. Group 1 [n=168 (35%)] patients did not experience any episode of AR. Group 2 [n=169 (35%)] patients had one or more episodes of AR and received high doses of steroids. Group 3 [n=141 (30%)] patients had more than one episode of AR and received anti‐lymphocyte antibodies in addition to high doses of steroids. Infections were more common in Groups 2 and 3 but only cytomegalovirus (CMV) disease occurred earlier in patients treated with lympholytics. Given the high incidence and early onset of CMV disease in patients receiving lympholytics and considering that an effective prophylactic protocol remains undetermined, pre‐emptive treatment with ganciclovir in this high risk group appears justified.
Immunization of renal transplant recipients with pneumococcal polysaccharide vaccine
Authors: Kazancıoğlu Rümeyza , Sever Mehmet Ş , Yüksel‐Önel Derya , Eraksoy Haluk , Yıldız Alaattin , Çelik A Vedat , Kayacan Seyit M , Badur Selim
Published: March 2003

Background: Streptococcus pneumoniae, a common pathogen leading to pneumonia, is a cause of morbidity and mortality in immunosuppressed patients. Vaccination against this agent can be recommended for immunosuppressed patients, including those with chronic renal failure, nephrotic syndrome and renal transplant recipients; however, a diminished immune response and loss of protective antibodies have been observed.Patients and methods: In our prospective study, the efficacy and side effects of polyvalent pneumococcal vaccination were investigated in renal transplant recipients. A total of 21 patients (6 female, 15 male) with well‐functioning renal allografts, who had transplant surgery at least 2 months before, were included in the study. The patients were stratified according to the immunosuppressive protocol and 8 received double, while 13 received triple, immunosuppresive agents. After obtaining basal serum samples, all cases were vaccinated with the 0.5 mL intramuscular administration of polyvalent polysaccharide pneumococcal vaccine (Pneumo 23 Pasteur–Merieux, lot No: K 1131).Results: Following a mean of 6 wk in all patients and also a mean of 12 wk in 12 patients, serum samples were again obtained to measure pneumococcal antibodies. Antibody titers following 6 and 12 wk of vaccination were significantly higher, as compared with basal values in all patients, except one. These titers did not show any statistically significant difference between double and triple therapies. There was no significant difference between the 12th and 6th wk postvaccination antibody titers. No systemic or local adverse effects were observed.Conclusion: Pneumococcal vaccination is safe and effective in patients with well‐functioning renal allografts, at least in the short term. This vaccination policy may be useful for preventing invasive pneumococcal disease in immunosuppressed patients.
Erythropoiesis and renal transplant pregnancy
Authors: Magee Laura A , Von Dadelszen Peter , Darley John , Beguin Yves
Published: March 2003

Objective. To examine erythropoiesis in renal transplant pregnancies.  Methods. Retrospective cohort study of 30 renal transplant cases and 30 age, smoking and parity‐matched healthy controls with normal index pregnancy. Retrospective chart review and assay of frozen antenatal serum (for serum erythropoietin concentration [serum EPO]), transferrin receptor protein [TfR], ferritin, folate and B12) were performed. The linear regression equation for normal pregnancy controls was used to calculate predicted [serum EPO] and the observed/predicted (O/P) log [serum EPO] was plotted. The relationship between [serum EPO] and haemoglobin (Hb) among transplant cases was considered to be different from that among controls if the slope of the O/P log [serum EPO] versus Hb regression was significantly different from zero.  Results. The transplant (14 cadaveric) to conception interval was (median [range]) 33.5 [4, 189] months. Immunosuppressants were azathioprine (n=25), cyclosporine (n=22) and/or prednisone (n=25). Cases were more often primiparous (20 vs. 7 [controls]; p=0.01), had pre‐existent hypertension (20 vs. 0 [controls]; p<0.001), developed new/increased hypertension or pre‐eclampsia (28 vs. 0 [controls]; p<0.001) and an antenatal rise in creatinine (14 vs. 2 [controls]; p<0.001). In early pregnancy, cases had similar EPO (15.2 [2.6, 84.6] vs. 15.7 [6.4, 41.0] [controls] U/L) but lower Hb (101 [65, 129] vs. 116 [106, 150] g/L; p<0.001). Twenty‐two (73%) cases had Hb<100 g/L (vs. 4 [controls]; p<0.0001); Hb was comparable at 6 wk postpartum. With advancing gestational age (GA), Hb remained stable and serum EPO increased in both groups. The slope of the O/P log [serum EPO] versus Hb for transplant cases was significantly different from zero within both the 17–28 wk (slope±SEM: 0.010±0.002; p<0.0001) and the 29–42 wk GA categories (0.006±0.003; p=0.02). Cases showed smaller rises in serum TfR (change 481 [−1 471, 2 780]) vs. 1119 [−698, 4 195] [controls] ng/mL; p=0.005).  Conclusions. Anaemia frequently complicates renal transplant pregnancies, in which serum EPO is inappropriately low and the rate of erythropoiesis blunted.
The beneficial effects of calcium channel blockers on long‐term kidney transplant survival are independent of blood‐pressure reduction
Authors: Mehrens Thomas , Thiele Stefanie , Suwelack Barbara , Kempkes Manuela , Hohage Helge
Published: March 2003

There is a growing body of evidence suggesting that calcium channel blockers (CCB) exert beneficial effects on kidney transplant survival. However, it is not completely understood if these agents act independently of blood‐pressure reduction. In the present study, the 5‐yr follow‐up of 45 kidney transplant recipients receiving CCB during the 60‐month follow‐up period was compared to that of recipients with lower blood pressure and an antihypertensive treatment without CCB. During the whole follow‐up, systolic (127.4±2.5 vs. 139.4±2.1 mmHg, p<0.05) as well as diastolic blood pressure (78.8±1.1 vs. 84.8±1.8 mmHg, p<0.05) was higher in the group receiving CCB. Moreover, in CCB‐treated recipients, a significant (p<0.05) higher increase in proteinuria was detected (from 759±120 to 1690±359 mg/24 h vs. 180±45 to 340±45 mg/24 h). Despite higher blood pressure and higher proteinuria, the increase in serum creatinine in the group of CCB‐treated recipients was significantly lower (0.01 mg/dL/month) in comparison to that of the controls (0.02 mg/dL/month, p<0.05). Moreover, the 5‐yr transplant survival was significantly higher in CCB‐treated recipients (62.3 vs. 31.8%, p<0.05). The results of the present study further support the beneficial effects of CCB in kidney transplant recipients, which are independent of blood‐pressure reduction.
Effect of homocysteine on carotid intima‐media thickness after renal transplantation
Authors: Suwelack Barbara , Gerhardt Ulf , Witta Jan , Rahn Karl Heinz , Hohage Helge
Published: March 2003

The common carotid intima‐media thickness (CC IMT) is a strong predictor for cardiovascular disease in patients with end‐stage renal failure. However, little is known about possible associations between potential cardiovascular risk factors such as serum total homocysteine concentrations (tHcy) and the CC IMT. Thus, we investigated (a) the course of tHcy levels after renal transplantation (RTX) and (b) the relationship between CC IMT and tHcy in 53 renal allograft recipients with chronic renal failure before transplantation and 3, 6, and 12 months after transplantation. Exclusion criteria were volume overload, symptomatic coronary artery disease, symptomatic cerebrovascular disease, peripheral artery disease, heart failure, valvular heart disease, diabetes mellitus, severe hypercholesterolemia, and blood pressure above 159/89 mmHg at the time of the investigation. In all renal allograft recipients, a carotid high‐resolution B‐mode ultrasound measurement of the CC IMT was performed.  Eighteen patients had normal (<20 μmol/L) pre‐transplant (U0) tHcy, 25 had moderately elevated (20–40 μmol/L) pre‐transplant (U0) tHcy, and 10 had severely elevated (>40 μmol/L) pre‐transplant (U0) tHcy. After 12 months of follow‐up time (U12), no statistically significant differences concerning the tHcy levels could be detected between the groups (average serum tHcy 16.4 μmol/L±1.1 μmol/L). The CC IMT did not differ significantly between the three tHcy groups at any time within the present follow‐up. This was also true for the ‘wall‐to‐lumen ratio’. A multiple forward stepwise regression analysis showed that the reduction of the CC IMT was positively correlated with gender (p<0.01), glucose levels at U12 (p<0.05; r2=0.96), systolic arterial blood pressure at U12 (p<0.05; r2=0.97), and with the intact parathyroid hormone levels at U0 (p<0.01; r2=0.98).  In conclusion, (a) tHcy decreases significantly after RTX, but (b) does not influence the CC IMT thickness independently.
Conversion from cyclosporin A to tacrolimus is safe and decreases blood pressure, cholesterol levels and TGF‐β1 type I receptor expression
Authors: Baan Carla C , Van Riemsdijk‐van Overbeeke Iza C , Balk Aggie HMM , Vantrimpont Pascal MAJ , Mol Wendy M , Knoop Chris J , Niesters Hubert GM , Maat Lex PWM , Weimar Willem
Published: March 2003

To determine whether conversion from cyclosporin A (CsA) to tacrolimus (TAC)‐based immunosuppressive therapy is safe and might lead to improvement in the clinical side effect profile we studied 55 cardiac allograft recipients. Ten stable patients were electively converted (0.2–1.5 yr after transplantation; group I) and 45 patients were converted on indication (0.5–14 yr after transplantation; group II).  We studied blood pressure, cholesterol level and renal function in all patients. To unravel the mechanisms by which CsA may exert its toxic effects and to evaluate whether conversion is associated with immune activation, we analyzed the transforming growth factor (TGF)‐β1 system and intragraft interleukin (IL)‐2 and IL‐15 mRNA expression by real‐time reverse transcription‐polymerase chain reaction (RT‐PCR) and quantitative flow cytometry in the selectively converted patients (group I).  Conversion did not result in immune activation as no clinical, histological or molecular signs of immune activation (increased intragraft IL‐2 and IL‐15 messenger RNA (mRNA) expression) leading to rejection were found. It did not improve renal function neither in patient group I nor in patient group II. However, after conversion the blood pressure decreased (group I: systolic 154±16 vs 143±21 mmHg, p=0.03, diastolic: 99±11 vs 90±11, p=0.02 and group II: systolic 155±17 vs 142±14, p<0.001, diastolic: 99±11 vs 91±8 mmHg, p<0.001). Likewise, the cholesterol levels improved (group I: 6.6±0.5 vs 5.7±0.3 mmol/L, p=0.001 and group II: 7.1±1.7 vs 6.1±1.7 mmol/L, p=0.001). When patients were treated with TAC the ongoing rejections (n=4) resolved and gum hyperplasia disappeared (n=5). Conversion was associated with a two‐fold lower TGF‐β1 type I receptor expression on peripheral lymphocytes and monocytes (p=0.02 and p=0.002, respectively).  Conversion from CsA to TAC results in improvement of blood pressure and cholesterol levels and does not induce immune activation. These beneficial effects were accompanied with lower TGF‐β1 type I receptor expression.
Good metabolic control using tacrolimus‐based immunosuppressants in primary cadaveric renal transplantation in Chinese – a preliminary report
Authors: Chow Kai Ming , Szeto Cheuk Chun , Li Philip Kam‐Tao
Published: March 2003

Metabolic complications are common with tacrolimus therapy. Recent evidence suggests that there is ethnical variability in the side‐effect profile of tacrolimus. We performed an open‐label study to examine the metabolic profile of tacrolimus‐based immunosuppressive therapy in 10 consecutive adult Chinese patients after cadaveric renal transplantation. One case withdrew because of parvovirus infection. The mean age of the remaining nine cases was 33 ± 2.9 yr. Mean tacrolimus whole blood trough level at 0 and 12 months were 11.4 ± 1.8 and 7.0 ± 0.7 ng/mL, respectively. The dosage at corresponding time points were 0.31 ± 0.001 and 0.10 ± 0.003 mg/kg, respectively. We found no difference in lipid profile, blood pressure control, and most importantly, fasting glucose level, before and 1 yr after tacrolimus therapy. Standard 75‐g oral glucose tolerance test and whole blood HbA1c level were normal in all patients. Our preliminary data suggest good short‐term safety among Chinese renal transplantation recipients after tacrolimus‐based immunosuppressants, with a very low incidence of hyperglycemia, hypertension and dyslipidemia. The long‐term implications and the underlying explanation for this ethnical difference require further investigations.
Diabetic muscle infarction after simultaneous pancreas‐kidney transplant
Authors: Delis Spiros , Ciancio Gaetano , Casillas Javier , Figueiro Jose , Garcia Alvaro , Miller Joshua , Burke George W
Published: March 2003

Diabetic muscle infarction (DMI) is a rare entity that occurs in patients with long‐standing type 1 insulin dependent diabetes mellitus (IDDM). We describe DMI occurring on an average of 5 months after SPK in four patients with IDDM and end stage renal disease (ESRD). These patients had evidence of other long‐term diabetic complications including retinopathy and neuropathy, as well as microangiopathy and hypercoagulability, both of which are pre‐disposing factors for DMI. The etiology of DMI is not well understood. Despite establishment of normoglycemia after kidney–pancreas transplantation, DMI may occur as a result of tissue damage/fragility secondary to the pre‐existing long‐term labile glycemic control and hypertension. This may be exacerbated by the pro‐coagulant effects of the calcineurin‐inhibitors and the use of steroids as part of the immunosuppressive regimen.
A theoretical reappraisal of mixed states: dysphoria as a third dimension
Authors: Dayer Alexandre , Aubry Jean‐Michel , Roth Loraine , Ducrey Séverine , Bertschy Gilles
Published: March 2003

Mixed states are heterogeneous clinical entities difficult to define precisely. The stringent actual DSM IV criteria are unsatisfactory for current clinical use. Many frequently encountered mixed patients benefit without an accurate diagnosis from biological therapeutic interventions such as the introduction of mood stabilizers. We propose a brief review of the definition and characteristics of mixed states and propose a new approach to the typology of mixed states. Based on recent literature data, we add to the depressive and manic syndrome the concept of dysphoria as a third dimension. Integrating this three dimensional approach with recent factor analysis, we describe in addition to the DSM IV mixed state (type I) two new subtypes of mixed states (type IIM and IID). This new typology can give the clinician a more accurate understanding of the complex and polymorphous reality of mixed states and help him make more specific therapeutic interventions. These subtypes of mixed states will need validation through prospective clinical studies. Biological differences, differential outcome over time, and differential response to treatment will be important validation criteria.
Genetic factors and treatment of mood disorders
Authors: Alda Martin
Published: March 2003

Objectives:
This paper reviews the pharmacogenetics of mood disorders.   Methods: We have searched the literature for published studies and abstracts relevant for genetic effects in acute antidepressant treatment and in long‐term prophylactic treatment.   Results: The most promising findings to date show an association of the serotonin transporter (5‐HTT) gene and the response to serotonin reuptake inhibitors. Genetic factors also appear to play a significant role in the outcome of long‐term lithium treatment. The phenotype of lithium‐responsive bipolar disorder is associated with stronger genetic effects as well as with an increased phenotypic homogeneity.   Conclusions: Genetic factors likely influence treatment response in mood disorders. Clarifying their precise role will have implications for treatment as well as for understanding the pathophysiological mechanisms of these disorders.
Insight into illness in patients with mania, mixed mania, bipolar depression and major depression with psychotic features
Authors: Dell'Osso Liliana , Pini Stefano , Cassano Giovanni B , Mastrocinque Concettina , Seckinger Regine Anna , Saettoni Marco , Papasogli Alessandra , Yale Scott A , Amador Xavier F
Published: March 2003

Dell'Osso L, Pini S, Cassano GB, Mastrocinque C, Seckinger RA, Saettoni M, Papasogli A, Yale SA, Amador XF. Insight into illness in patients with mania, mixed mania, bipolar depression and major depression with psychotic features. Bipolar Disord 2002: 4: 315–322. © Blackwell Munksgaard 2002

Background:
Poor insight into illness is a common feature of bipolar disorder and one that is associated with poor clinical outcome. Empirical studies of illness awareness in this population are relatively scarce with the majority of studies being published over the previous decade. The study reported here sought to replicate previous report findings that bipolar patients frequently show high levels of poor insight into having an illness. We also wanted to examine whether group differences in insight exist among bipolar manic, mixed and unipolar depressed patients with psychotic features.

Methods:
A cohort of 147 inpatients with DSM‐III‐R bipolar disorder and 30 with unipolar depression with psychotic features, were evaluated in the week prior to discharge using the Structured Clinical Interview for DSM‐III‐R‐Patient Edition (SCID‐P), the Brief Psychiatric Rating Scale (BPRS) and the Scale to assess Unawareness of Mental Disorder (SUMD).

Results:
Insight into specific aspects of the illness was related to the polarity of mood episode: patients with mania showed significantly poorer insight compared with those with mixed mania, bipolar depression and unipolar depression. A linear regression analysis using SUMD score as the dependent variable and symptoms of mania as the independent variable found that specific manic symptoms did not account for level of insight. Similar results were obtained when the mean insight scores of patients with and without grandiosity were contrasted.

Conclusions:
We hypothesize that the lack of association between level of insight and total number of manic symptoms or with specific manic symptoms may be related to the persistence of subsyndromal symptoms in patients remitting from a manic episode.
Right prefrontal TMS versus sham treatment of mania: a controlled study
Authors: Kaptsan Alex , Yaroslavsky Yuri , Applebaum Julia , Belmaker RH , Grisaru Nimrod
Published: March 2003

Objective:  Left prefrontal transcranial magnetic stimulation (TMS) has been reported to have ECT‐like effects in depression and we therefore planned a study of TMS in mania. Sixteen patients completed trial of right versus left prefrontal TMS at 20 Hz, 2‐sec duration per train, 20 trains per day for 10 treatment days. Mania was evaluated using the Mania Scale, the Brief Psychiatric Rating Scale and the Clinical Global Impression. Significantly more improvement was observed in patients treated with right prefrontal TMS than with left prefrontal. We now report a follow‐up study of right active TMS versus right sham TMS with the same indications and parameters.

Methods:  Twenty‐five patients entered and 19 completed right TMS versus sham right TMS.

Results:  Right TMS was no more effective than sham TMS.

Conclusions:  It is possible that the previous results were due to an effect of left TMS to worsen mania. Alternatively, it is noted that the present patient group had much more psychosis than the previous study of TMS in mania, and depression studies have reported that psychosis is a poor prognostic sign for TMS response.
A new bipolar spectrum concept: a brief review
Authors: Angst Jules , Gamma Alex
Published: March 2003

Angst J, Gamma A. A new bipolar spectrum concept: a brief review.  Bipolar Disord 2002: 4(Suppl. 1): 11–14. © Blackwell Munksgaard, 2002

Research on the broad bipolar spectrum is dependent on the definition of hypomania. We recently proposed a new, softer syndromal definition with clinical validity. This broadens the diagnosis of bipolar II (BP‐II) disorder at the expense of major depressive disorder (MDD). There is evidence for a third group of suspected BP‐II manifesting major depression plus hypomanic symptoms. The two bipolar‐II groups together are as prevalent as MDD. A new concept of minor bipolar disorder embracing dysthymia, minor and recurrent brief depression with hypomanic syndromes and symptoms is discussed. Some methodological pitfalls of research on drug‐induced hypomania as an element of the bipolar spectrum are also summarized.
Dimensions of psychopathology in bipolar disorder versus other affective and non‐affective psychoses among an epidemiologically complete population
Authors: Scully PJ , Owens JM , Kinsella A , Waddington John L
Published: March 2003

Scully PJ, Owens JM, Kinsella A, Waddington JL. Dimensions of psychopathology in bipolar disorder versus other affective and non‐affective psychoses among an epidemiologically complete population. Bipolar Disord 2002: 4(Suppl. 1): 43–44. © Blackwell Munksgaard, 2002
Can we conduct some large simple trials in bipolar disorder?
Authors: Geddes John R
Published: March 2003

Geddes JR. Can we conduct some large simple trials in bipolar disorder?  Bipolar Disord 2002: 4(Suppl. 1): 62–63. © Blackwell Munksgaard, 2002
Outcome measures in treatment trials in bipolar disorder
Authors: Nolen WA
Published: March 2003

Nolen WA. Outcome measures in treatment trials in bipolar disorder.  Bipolar Disord 2002: 4(Suppl. 1): 64–65. © Blackwell Munksgaard, 2002
Response to ECT in major depression: are there differences between unipolar and bipolar depression?
Authors: Grunhaus L , Schreiber S , Dolberg OT , Hirshman S , Dannon PN
Published: March 2003

Grunhaus L, Schreiber S, Dolberg OT, Hirshman S, Dannon PN. Response to ECT in major depression: are there differences between unipolar and bipolar depression?  Bipolar Disord 2002: 4(Suppl. 1): 91–93. © Blackwell Munksgaard, 2002
The long‐term outcome of retropubic urethrocystopexy (sutures and fibrin sealant) and pubococcygeal repair
Authors: LALOS OTHON , BERGLUND ANNA‐LENA , BJERLE PER
Published: March 2003

Background. To evaluate the results of retropubic urethrocystopexy (with sutures and fibrin sealant) and pubococcygeal repair five to seven years postoperatively.

Material and methods. Thirty women with genuine stress urinary incontinence were subjected to retropubic urethrocystopexy (n=30) and 15 women to pubococcygeal repair (n=15). The preoperative assessment included both subjective and objective methods. The results evaluated three months, one year and five to seven years after the surgical treatment.

Results. One year after surgery 71% of the women in the urethrocystopexy group reported that they were continent, compared with only 43% five to seven years after surgery. In the pubococcygeal repair group 80% were continent at one‐year follow‐up, compared with 60% at the long‐term follow‐up. According to pad test 79% of the women in the urethrocystopexy group had ceased leaking urine at minimal activity and 64% at maximal activity five to seven years after surgery. However, in the pubococcygeal repair group the corresponding percentage was 71% under both conditions. Intravesical pressure and Body Mass Index increased significantly in the whole group but urethra conductance and maximal urine flow decreased only in the urethrocystopexy group five to seven years after the surgical treatment.

Conclusions. Accurate assessment of the results of any surgical treatment of stress urinary incontinence is difficult. During long term follow‐up period significant changes may occur among the women, e.g. menopause and increase of Body Mass Index both predisposing to urinary incontinence.
Increased risk of preterm delivery with elevated maternal alpha‐fetoprotein and plasma zinc levels in African‐American women
Authors: NEGGERS YASMIN H. , GOLDENBERG ROBERT L. , DUBARD MARY B. , CLIVER SUZANNE P.
Published: March 2003

Background. This study evaluated the relationship of maternal serum alpha‐fetoprotein (MSAFP) and plasma zinc levels (PZn) to pregnancy outcome.

Methods. The subjects for this investigation consisted of 917 African‐American women, who on registration for prenatal care between 7–22 weeks gestational age (GA), had PZn levels determined and also had MSAFP recorded in their charts.

Results. MSAFP levels greater than the 90th percentile significantly increased the risk of PTD (adjusted odds ratio or AOR=2.5, 95% C.I.=1.5−4.2) but not of IUGR. There was no significant relationship between maternal PZn level and PTD or IUGR. When subjects were stratified by MSAFP levels, in women with MSAFP greater than the 90th percentile, the AOR for PTD was 4.0 (95% C.I.=1.2−13.5) for women with PZn levels greater than the median vs. those with PZn equal to or less than the median. In women with MSAFP equal to or less than the 90th percentile, there was no such difference. Multiple regression analyses, using GA at birth as the dependent variable, indicated an interaction between MSAFP and PZn levels.

Conclusion. In this population, the adverse pregnancy outcome associated with elevated MSAFP was seen only in women with PZn levels greater than the median. The reason for this association is not currently apparent.
The prevalence of anemia in pregnant Nepali women – a study in Kathmandu
Authors: BONDEVIK GUNNAR T. , ULSTEIN MAGNAR , LIE ROLV T. , RANA GEETHA , KVÅLE GUNNAR
Published: March 2003

Background. Anemia in pregnancy is associated with maternal and perinatal morbidity and mortality. The World Health Organization has suggested that where up‐to‐date information is not available, prevalence studies should be undertaken.

Methods. The distribution of hematocrit in 2280 pregnant women attending Patan Hospital, Kathmandu, for their first antenatal visit in a twelve month period, 1994–95, was studied. Anemia was defined as a hematocrit value ≤34% in the first and third trimesters, or ≤33% in the second trimester. Severe anemia was defined as a hematocrit value ≤24%. The prevalence of anemia and severe anemia, and associations with socio‐demographic (age, ethnic group, living area, maternal and paternal education and occupation) and biological (height, body mass index, parity, gestation) variables were investigated.

Results. The hematocrit values ranged from 11–49% with a mean value of 32.6% (s.d. 3.9). The prevalences of anemia and severe anemia were 62.2% and 3.6%, respectively. High prevalence of anemia was observed among teenagers, farmers, women of short height, the ethnic groups Lama/Sherpa/Tamang, and women married to industrial workers or illiterate men. Also, the risk of anemia increased with gestation. Work within the service professions, higher education and high body mass index, were associated with a lower risk of anemia.

Conclusions. A high prevalence of anemia among pregnant women in Kathmandu was observed. The hematocrit values were related to socio‐demographic and biological factors. In order to plan focused and effective intervention, studies on the etiology of anemia among pregnant women in rural and urban areas of Nepal need to be carried out.
Adequate timing of fetal ultrasound to guide metabolic therapy in mild gestational diabetes mellitus
Authors: ROSSI GABRIELE , SOMIGLIANA EDGARDO , MOSCHETTA MARTA , BOTTANI BARBARA , BARBIERI MAURIZIO , VIGNALI MARIO
Published: March 2003

Background. Ultrasound assessment of abdominal circumference early in the third trimester had been proposed to introduce insulin therapy in order to prevent fetal overgrowth in women with mild gestational diabetes mellitus. The purpose of this study was to investigate adequate weeks gestation timing for testing this parameter.

Methods. One hundred and forty‐one women were included in a randomized trial. Seventy‐three women were evaluated at both 28 and 32 weeks gestation whereas 68 women were investigated only at 32 weeks gestation. In both groups, insulin therapy was promptly started when abdominal circumference exceeded the 75th percentile. Macrosomic rates were compared using the Fisher's exact test.

Results. Twenty‐nine women whose fetal abdominal circumference exceeded the 75th percentile were considered eligible for insulin therapy. In this group, we observed a statistically significant increase in the percentage of macrosomic infants born from women whose ultrasound abdominal circumference assessment was performed only at 32 weeks gestation when compared to women evaluated at both 28 and 32 weeks gestation (71.43% vs 33.33%, p<0.05).

Conclusions. Our results support the need for fetal ultrasound at 28 weeks gestation to direct metabolic therapy since insulin administration introduced after 32 weeks gestation has a poor effect on fetal growth.
Management of pregnancies with suspected intrauterine growth retardation in Sweden
Authors: BRODSZKI JANA , MARŠÁL KAREL
Published: March 2003

Background. Diagnosis and management of intrauterine growth retardation during pregnancy remain a major challenge in obstetric care. The objective of this survey was to evaluate the routine clinical management of pregnancies with suspected intrauterine growth retardation at obstetric departments in Sweden.

Methods. In 1997, a questionnaire was sent to all 59 obstetric departments in Sweden. Forty‐two departments, caring for 83% of all deliveries in Sweden, replied. Four major topics were addressed: definition and diagnosis of intrauterine growth retardation; magnitude of the problem; clinical management; use of Doppler ultrasound in clinical decision‐making.

Results. Intrauterine growth retardation is diagnosed by a combination of serial fundal height measurements and ultrasonic fetal biometry at 40 departments, two departments perform routine fetal biometry at 32 weeks. The diagnosis is most often made at 32–36 gestational weeks. Five departments use 1.5 s.d. below the mean as cut‐off point for diagnosis of small for gestational age fetuses; 35 departments use mean – 2 s.d. and two departments mean – 2.5 s.d. Intrauterine growth retardation is suspected in 1.6–6.3% pregnancies. About 19% of patients with suspected intrauterine growth retardation are hospitalized. On average, 63% of all small‐for‐gestational age babies are diagnosed prenatally. Thirty‐nine out of 42 obstetric departments use formalized management protocols. All departments use cardiotocography, repeat ultrasound scans and Doppler ultrasound for antenatal surveillance.

Conclusions. In Swedish obstetric units, the diagnostic procedures and methods of fetal surveillance in pregnancies suspected of intrauterine growth retardation are more or less uniform. Doppler examination of umbilical artery is used at all responding departments and is considered a valuable asset in clinical decision‐making.
Influence of chorioamnionitis on survival and morbidity in singletons live‐born at <32 weeks of gestation
Authors: KOSUGE SHUICHI , OHKUCHI AKIHIDE , MINAKAMI HISANORI , MATSUBARA SHIGEKI , UCHIDA AKIRA , EGUCHI YUKARI , HONMA YOKO , SATO IKUO
Published: March 2003

Background. Chorioamnionitis (CAM) may accelerate lung maturation in fetuses. It is possible that CAM prevents infant death after live birth.

Methods. A retrospective study of live‐born singletons at <32 weeks of gestation between 1993 and 1997. Perinatal risk factors for adverse outcomes were analyzed using a logistic regression model, with special reference to the presence of histologically confirmed CAM. Adverse outcomes included infant death before 1 year of age, and survival with cerebral palsy and/or mental retardation.

Results. A total of 81 infants, weighing 1181±426 g, were born at 28.1±2.3 weeks of gestation. Of those, 15 (19%) died before 1 year of age, while 16 (20%) infants developed major handicaps by 1.5 years of age (six with cerebral palsy, eight with mental retardation, and two with both cerebral palsy and mental retardation). CAM, present in 44 women, was significantly associated with a reduced risk of death after live birth, with an odds ratio of 0.11 (p=0.01). Only the presence of such intracranial lesions as periventricular leukomalacia and intraventricular hemorrhage were significantly associated with an increased risk of major handicaps (odds ratio of 11.0, p=0.04). Adverse outcomes occurred in a similar proportion of infants in groups without CAM (14/37) and with CAM (17/44). However, among infants with adverse outcomes, the number of deaths was significantly higher in the group without CAM (10/14) vs. with CAM (5/12) (p<0.05).

Conclusions. The presence of CAM may somehow prevent infant death after live birth. Larger studies are required to confirm this phenomenon.
Socio‐economic, demographic and obstetric risk factors for late fetal death of unknown etiology in Lithuania:
Authors: Maleckiene Laima , Nadisauskiene Ruta , Bergström Staffan
Published: March 2003

Background. The purpose of this study was to evaluate the association between third trimester unexplained prelabor fetal deaths and various socio‐economic, demographic and obstetric factors in Lithuania.

Methods. A case–referent study on 58 women with third trimester fetal death and 116 women with live fetus at term was carried out. Inclusion criteria for women in the first group (cases) were: prelabor fetal death of unknown etiology, singleton pregnancy >26 weeks of gestation and intact fetal membranes. For each case two referent women were recruited, admitted during the same period in active phase of labor at term (>37 weeks of gestation) with intact fetal membranes and fetus alive. Data were obtained by interview, anthropometry and by reviewing the medical records. Several potential socio‐economic, demographic and obstetrical risk factors for unexplained fetal death were investigated.

Results. Univariate analyses determined several factors that were associated with fetal death of unknown etiology: low educational level, single marital status, low income, etc. After secondary logistic regression analysis only three independent variables remained significantly associated with otherwise unexplained stillbirth: small for gestational age fetus (OR 29.6; 95% CI 6.2–141.6), low income (OR 7.4; 95% CI 3.1–17.6), and maternal white blood cell count more than 16,000/mm3 (OR 5.4; 95% CI 1.4–21.6). Body mass index, smoking, occupation of women and other evaluated parameters were not confirmed to be significant risk factors.

Conclusion. Small for gestational age fetus, low income and elevated maternal white blood cell count are factors significantly associated with late prelabor fetal death in Lithuania.
Tumor cell spillage to the vaginal cavity and vaginal stump during the surgery of endometrial carcinoma
Authors: Ryo Eiji , Yorinaga Yasuko , Nagasaka Tsuneki , Yoshikawa Hiroyuki , Taketani Yuji
Published: March 2003

Background. Our purpose was to investigate the spillage of the endometrial carcinoma cells to the vaginal cavity and vaginal stump during the surgery.

Methods. Cytologic examination of specimens obtained from the vaginal cavity and vaginal stump during surgery performed on 15 patients with endometrial carcinoma. And the risk factors of carcinoma cell spillage to the vaginal cavity were investigated.

Results. Carcinoma cells from the vaginal cavity were negative for nine patients and positive for six patients. Those from the vaginal stump were negative for l4 patients and positive for one patient. In one patient, both were positive. Total abdominal hysterectomy might be one risk of carcinoma cell spillage to the vaginal cavity compared with modified radical hysterectomy and radical hysterectomy.

Conclusions. Endometrial carcinoma cells were spilled into the vaginal cavity in not a few cases and their spillage from there to the vaginal stump could follow during the surgery.
Influences of perinatal factors on cord blood thyroid‐stimulating hormone level
Authors: Chan Louis Yik‐Si , Leung Tse Ngong , Lau Tze Kin
Published: March 2003

Background. Cord blood thyroid‐stimulating hormone level is affected by various perinatal factors. The aim of this study is to investigate the relative impact of these factors on the cord blood thyroid‐stimulating hormone results in singleton pregnancies.

Methods. The study group consisted of 20,086 consecutive singleton deliveries over a 3 year period. The effect of mode of delivery, infant sex, gestation at birth, birth weight, and duration of labor on the incidence of false elevation of cord blood thyroid‐stimulating hormone was assessed by univariate analysis and logistic regression.

Results. There was an independent positive association between false elevation of cord blood thyroid‐stimulating hormone (≥15.0 mIU/L) and birth weight (p=0.005), male infant sex (p<0.001), and instrumental delivery (p<0.001). Both elective and emergency cesarean section were negatively associated with elevated cord thyroid‐stimulating hormone level (p<0.001). When the cutoff level was raised to 40.0 mIU/L, none of the variables examined were significant. The incidence of false positive tests (≥15.0 mIU/L) was higher in neonates born by cesarean section for failed instrumental delivery and fetal distress than for failure to progress of labor (34.7% vs 4.5% vs 1.3% respectively, p<0.001).

Conclusions. While the incidence of false positive screening was significantly affected by various perinatal factors when the thyroid‐stimulating hormone cutoff level is low, it was unaffected at a high cutoff level. The present study also provides further evidence that cord blood thyroid‐stimulating hormone level reflects fetal response to perinatal stress events.