Association of location of BRCA1 and BRCA2 mutations with benefit from olaparib and bevacizumab maintenance in high-grade ovarian cancer: phase III PAOLA-1/ENGOT-ov25 trial subgroup exploratory analysis.

BACKGROUND: In the phase III PAOLA-1 study, the addition of maintenance olaparib to bevacizumab in patients with newly diagnosed high-grade ovarian cancer (HGOC) resulted in prolonged progression-free survival (PFS), particularly for homologous recombination deficiency-positive tumors, including those with a BRCA mutation (BRCAm). The magnitude of benefit from olaparib and bevacizumab according to the location of mutation in BRCA1/BRCA2 remains to be explored. PATIENTS AND METHODS: Patients with advanced-stage HGOC responding after platinum-based chemotherapy + bevacizumab received maintenance therapy bevacizumab (15 mg/kg q3w for 15 months) + either olaparib (300 mg b.i.d. for 24 months) or placebo. PFS was analyzed in the subgroup of patients with BRCA1m/BRCA2m according to mutation location in the functional domains of BRCA1 [Really Interesting Gene (RING), DNA-binding domain (DBD), or C-terminal domain of BRCA1 (BRCT)] and BRCA2 [RAD51-binding domain (RAD51-BD); DBD]. RESULTS: From 806 randomized patients, 159 harbored BRCA1m (19.7%) and 74 BRCA2m (9.2%). BRCA1m in RING, DBD, and BRCT domains was detected in 18, 40, and 33 patients, and BRCA2m in RAD51-BD and DBD in 36 and 13 patients, respectively. After a median follow-up of 25.5 months, benefit from maintenance olaparib + bevacizumab was observed irrespective of location of BRCAm. The benefit was particularly high for those with BRCA1m located in the DBD, with 24-month PFS estimated to be 89% and 15% [olaparib + bevacizumab versus placebo + bevacizumab hazard ratio = 0.08 (95% confidence interval 0.02-0.28); interaction P = 0.03]. In BRCA2m patients, 24-month PFS rates for those with mutations located in the DBD were 90% and 100% (olaparib + bevacizumab versus placebo + bevacizumab), respectively. CONCLUSIONS: Advanced-stage BRCA-mutated HGOC patients reported PFS benefit from maintenance olaparib and bevacizumab regardless of mutation location. The benefit is particularly high for patients with mutations located in the DBD of BRCA1. Mutations located in the DBD of BRCA2 are also associated with excellent outcome.

Olaparib plus bevacizumab first-line maintenance in ovarian cancer: final overall survival results from the PAOLA-1/ENGOT-ov25 trial.

BACKGROUND: In the PAOLA-1/ENGOT-ov25 primary analysis, maintenance olaparib plus bevacizumab demonstrated a significant progression-free survival (PFS) benefit in newly diagnosed advanced ovarian cancer patients in clinical response after first-line platinum-based chemotherapy plus bevacizumab, irrespective of surgical status. Prespecified, exploratory analyses by molecular biomarker status showed substantial benefit in patients with a BRCA1/BRCA2 mutation (BRCAm) or homologous recombination deficiency (HRD; BRCAm and/or genomic instability). We report the prespecified final overall survival (OS) analysis, including analyses by HRD status. PATIENTS AND METHODS: Patients were randomized 2 : 1 to olaparib (300 mg twice daily; up to 24 months) plus bevacizumab (15 mg/kg every 3 weeks; 15 months total) or placebo plus bevacizumab. Analysis of OS, a key secondary endpoint in hierarchical testing, was planned for ∼60% maturity or 3 years after the primary analysis. RESULTS: After median follow-up of 61.7 and 61.9 months in the olaparib and placebo arms, respectively, median OS was 56.5 versus 51.6 months in the intention-to-treat population [hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.76-1.12; P = 0.4118]. Subsequent poly(ADP-ribose) polymerase inhibitor therapy was received by 105 (19.6%) olaparib patients versus 123 (45.7%) placebo patients. In the HRD-positive population, OS was longer with olaparib plus bevacizumab (HR 0.62, 95% CI 0.45-0.85; 5-year OS rate, 65.5% versus 48.4%); at 5 years, updated PFS also showed a higher proportion of olaparib plus bevacizumab patients without relapse (HR 0.41, 95% CI 0.32-0.54; 5-year PFS rate, 46.1% versus 19.2%). Myelodysplastic syndrome, acute myeloid leukemia, aplastic anemia, and new primary malignancy incidence remained low and balanced between arms. CONCLUSIONS: Olaparib plus bevacizumab provided clinically meaningful OS improvement for first-line patients with HRD-positive ovarian cancer. These prespecified exploratory analyses demonstrated improvement despite a high proportion of patients in the placebo arm receiving poly(ADP-ribose) polymerase inhibitors after progression, confirming the combination as one of the standards of care in this setting with the potential to enhance cure.

Breech progression angle: new feasible and reliable transperineal ultrasound parameter for assessment of fetal breech descent in birth canal.

OBJECTIVE: To assess the feasibility and reliability of transperineal ultrasound in the assessment of fetal breech descent in the birth canal, by measuring the breech progression angle (BPA). METHODS: Women with a singleton pregnancy with the fetus in breech presentation between 34 and 41 weeks' gestation were recruited. Transperineal ultrasound images were acquired in the midsagittal view for each woman, twice by one operator and once by another. Each operator measured the BPA after anonymization of the transperineal ultrasound images. BPA was defined as the angle between a line running along the long axis of the pubic symphysis and another line extending from the most inferior portion of the pubic symphysis tangentially to the lowest recognizable fetal part in the maternal pelvis. Each operator was blinded to all other measurements performed for each woman. Intra- and interobserver reproducibility of BPA measurement was evaluated using the intraclass correlation coefficient (ICC). To investigate the presence of any bias, intra- and interobserver agreement was also analyzed using Bland-Altman analysis. Student's t-test and Levene's W0 test were used to investigate whether a number of different clinical factors had an effect on systematic differences and homogeneity, respectively, between BPA measurements. RESULTS: Overall, 44 women were included in the analysis. BPA was measured successfully by both operators on all images. Both intra- and interobserver agreement analyses showed excellent reproducibility in BPA measurement, with ICCs of 0.88 (95% CI, 0.80-0.93) and 0.83 (95% CI, 0.71-0.90), respectively. The mean difference between measurements was 0.4° (95% CI, -1.4 to 2.2°) for intraobserver repeatability and -0.4° (95% CI, -2.6 to 1.8°) for interobserver repeatability. The upper limits of agreement were 12.0° (95% CI, 8.9-15.1°) and 13.6° (95% CI, 9.9-17.3°) for intra- and interobserver repeatability, respectively. The lower limits of agreement were -11.2° (95% CI, -14.3 to -8.1°) and -14.4° (95% CI, -18.2 to -10.7°) for intra- and interobserver repeatability, respectively. No systematic difference between BPA measurements was found on either intra- or interobserver agreement analysis. None of the clinical factors examined (maternal body mass index, maternal age, gestational age at the ultrasound scan and parity) showed a statistically significant effect on intra- or interobserver reliability. CONCLUSIONS: BPA represents a new feasible and highly reproducible measurement for the evaluation of fetal breech descent in the birth canal. Future studies assessing its usefulness in the prediction of successful external cephalic version and breech vaginal delivery are needed. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Is it safe to perform rectal anastomosis in gynaecological debulking surgery without a diverting stoma?

AIM: Colorectal resection is frequently performed during cytoreductive surgery for gynaecological malignancy. The aim of this study was to assess the safety of colorectal anastomosis, and especially low rectal anastomosis, in the absence of a protective stoma in patients with gynaecological cancer and peritoneal metastasis. METHOD: Patient data were retrospectively collected from a database for gynaecological cancer procedures carried out between January 2013 and July 2015. All patients who underwent a colorectal resection during cytoreduction were included in the study. The primary outcome was anastomotic leakage in the presence or absence of a diverting stoma. Secondary outcome parameters were complications and reoperations. RESULTS: In the period of study, 43 major colorectal procedures were performed on 37 women. The most common colorectal procedure was low rectal resection (n = 22; 59%) followed by anterior rectal resection (n = 7; 19%) and sigmoid resection (n = 4; 11%). Five (14%) patients underwent Hartmann's procedure. In three (8%) patients, a diverting loop ileostomy was created. CONCLUSION: Low rectal resection during debulking procedures for gynaecological cancers with peritoneal carcinomatosis can safely be performed by an experienced surgeon without a diverting stoma.

Plasma adrenomedullin levels in children with asthma: any relation with atopic dermatitis?

BACKGROUND: Asthma is a chronic, inflammatory disease of the airway, and adrenomedullin (ADM) may have some effects against bronchoconstriction. However, the role(s) of ADM in asthmatic children have not been evaluated yet. The aims of this study were to determine if there are any changes in plasma ADM levels during acute asthma attack, and to search for any association between allergen sensitivity and ADM level in asthmatic children. METHODS: Twenty-seven children with acute asthma attack, ranging in age from 5 to 15 years were investigated and compared with 20 controls. Plasma ADM levels (ng/mL) were measured by ELISA method. RESULTS: No significant difference was found in ADM levels between the controls and patients in either the acute attack or remission period. Plasma ADM levels were significantly higher in the acute attack (p=0.043) compared to the remission period in patients who were considered as having a "severe attack" according to GINA (Global Initiative for Asthma) classification. There were statistically significant correlations between the patients' AlaTOP and Food Panel 7 levels and plasma ADM levels in the acute attack period (p=0.010, p=0.001, respectively). The ADM levels in patients with a history of atopic dermatitis were significantly higher in the acute attack period compared to those without a history of atopic dermatitis (p=0.007). CONCLUSION: We speculate that ADM may have a role in children with atopic dermatitis, and may also have a role in the immuno-inflammatory process of asthma.

Sphingosine-kinase-1 expression is associated with improved overall survival in high-grade serous ovarian cancer.

PURPOSE: Sphingosine-kinase-1 (SPHK1) is a key enzyme of sphingolipid metabolism which is involved in ovarian cancer pathogenesis, progression and mechanisms of drug resistance. It is overexpressed in a variety of cancer subtypes. We investigated SPHK1 expression as a prognostic factor in epithelial ovarian cancer patients. METHODS: Expression analysis of SPHK1 was performed on formalin-fixed paraffin-embedded tissue from 1005 ovarian cancer patients with different histological subtypes using immunohistochemistry. Staining intensity of positive tumor cells was assessed semi-quantitatively, and results were correlated with clinicopathological characteristics and survival. RESULTS: In our ovarian cancer collective, high levels of SPHK1 expression correlated significantly with complete surgical tumor resection (p = 0.002) and lower FIGO stage (p = 0.04). Progression-free and overall survival were further significantly longer in patients with high-grade serous ovarian cancer and overexpression of SPHK1 (p = 0.002 and p = 0.006, respectively). CONCLUSION: Our data identify high levels of SPHK1 expression as a potential favorable prognostic marker in ovarian cancer patients.

Completion of radical hysterectomy does not improve survival of patients with cervical cancer and intraoperatively detected lymph node involvement: ABRAX international retrospective cohort study.

BACKGROUND: The management of cervical cancer patients with intraoperative detection of lymph node involvement remains controversial. Since all these patients are referred for (chemo)radiation after the surgery, the key decision is whether radical hysterectomy should be completed as originally planned, taking into account an additional morbidity associated with extensive surgical dissection prior to adjuvant treatment. The ABRAX study investigated whether completing a radical uterine procedure is associated with an improved oncological outcome of such patients. PATIENTS AND METHODS: We performed retrospective analyses of 515 cervical cancer patients (51 institutions, 19 countries) who were referred for primary curative surgery between 2005 and 2015 (stage IA-IIB, common tumour types) in whom lymph node involvement was detected intraoperatively. Patients were stratified according to whether the planned uterine surgery was completed (COMPL group, N = 361) or abandoned (ABAND group, N = 154) to compare progression-free survival. Definitive chemoradiation was given to 92.9% patients in the ABAND group and adjuvant (chemo)radiation or chemotherapy to 91.4% of patients in the COMPL group. RESULTS: The risks of recurrence (hazard ratio [HR] 1.154, 95% confidence intervals [CI] 0.799-1.666, P = 0.45), pelvic recurrence (HR 0.836, 95% CI 0.458-1.523, P = 0.56), or death (HR 1.064, 95% CI 0.690-1.641, P = 0.78) were not significantly different between the two groups. No subgroup showed a survival benefit from completing radical hysterectomy. Disease-free survival reached 74% (381/515), with a median follow-up of 58 months. Prognostic factors were balanced between the two groups. FIGO stage and number of pelvic lymph nodes involved were significant prognostic factors in the whole study cohort. CONCLUSION: We showed that the completion of radical hysterectomy does not improve survival in patients with intraoperatively detected lymph node involvement, regardless of tumour size or histological type. If lymph node involvement is confirmed intraoperatively, abandoning uterine radical procedure should be considered, and the patient should be referred for definitive chemoradiation. CLINICAL TRIALS IDENTIFIER: NCT04037124.

Influence of the relapse and remission periods on hearing status in children with minimal change nephrotic syndrome.

OBJECTIVE: Minimal change nephrotic syndrome (MCNS) is characterized by the onset of NS (Nephrotic Syndrome) without systemic disease, hypocomplementemia, or other serious signs of renal disease. Hearing status is not very well known in MCNS. Our objective was to address this question and to find out remission and relapse periods of the syndrome would affect the hearing of the patients. METHODS AND PATIENTS: Otologic status of 26 children with clinical MCNS was investigated in relapse and remission periods using audiometry and tympanometry. The pure tones that were obtained at the frequencies 250, 500, 1000, 2000, 4000 and 6000 Hz were noted. Pure tone averages (PTAs) were calculated at 500, 1000, 2000 and 4000 Hz frequencies. RESULTS: In both remission and relapse periods, PTA of the patients did not change and was 13 dB. The frequency specific pure tone results were not significantly different between the right and left ears of the patients as well as between the remission and relapse periods (p > 0.05). In the relapsing and remission periods, type A tympanogram was encountered in 86.4% and 92.3% of the ears, respectively. Type B tympanogram was encountered in 11.5% and 3.8% of the ears in the relapsing and remission periods, respectively. Type C tympanogram was encountered in 3.8% of the ears both in the relapsing and remission periods. Differences between the tympanometry results were not significant (p > 0.05). CONCLUSION: MCNS in childhood is not associated with an alteration in the hearing status, both in remission and relapse periods of the disease.

Myocardial functions of children with acute poststreptococcal glomerulonephritis.

Left ventricular function was investigated by two-dimensional and M-mode echocardiography in 35 patients with acute poststreptococcal glomerulonephritis and in 25 healthy controls. Six of these patients were found to have myocardial dysfunction during the acute congestive phase and convalescent phases of APSGN. One of these 6 patients, later, died. No correlations were determined between myocardial dysfunction and hypertension, cardiac failure, pericardial and pleural effusion. As a result, left ventricular function may be impaired in acute congestive phase of APSGN and this may affect the course and prognosis of the disease.

Interpupillary index: a new parameter for hypo-hypertelorism.

AIM: To establish a new clinical index to evaluate the presence of hypo-hypertelorism with greater accuracy. MATERIAL AND METHODS: After screening a wide range of population, 310 elementary school children (185 boys, 125 girls) aged 7-15 years were included in this study. For this cross-sectional study, a millimetre ruler was used. The anatomical interpupillary distance was measured by a modified Viktorin's method. In addition, inner and outer intercanthal distances were obtained. The data were analyzed by Student's t-test for two independent samples using SPSS for Windows. There were children with clinical hypertelorism (n = 92, group 1), children with large fronto-occipital circumference (FOC) (n = 101, group 2), and age- and sex-matched normal controls (n = 117, group 3). Due to variations in FOC among healthy subjects, we introduced a new practical concept for evaluation of interpupillary distance, namely the interpupillary index, the simple product obtained by dividing the interpupillary distance by the FOC, multiplied by 100. RESULTS: The overall idiopathic benign macrocephalic children (group 2) had significantly (p < 0.001) larger interpupillary distances (6.13 +/- 0.36 cm) and FOCs (56.99 +/- 1.46 cm) than those of normal controls (5.70 +/- 0.26cm and 52.82 +/- 1.22 cm, respectively). But, the difference between the combined product of interpupillary distance and FOC, the interpupillary index, was not significant (10.76 +/- 0.50 and 10.79 +/- 0.35, respectively) (p > 0.05). On the other hand, the children with hypertelorism had significantly (p < 0.001) larger interpupillary distances (6.47 +/- 0.29cm) and FOCs (54.90 +/- 2.18cm) when compared with the controls. In addition, the interpupillary index was significantly (p < 0.001) higher (11.80 +/- 0.45) than both macrocephalic children (10.76 +/- 0.50) and controls (10.79 +/- 0.35). Intercanthal distances and intercanthal index of hyperteloric children were also significantly (p<0.001) larger than both macrocephalic children and controls. CONCLUSION: This new index offers a new concept for more accurate evaluation of the presence of ocular hypo-hypertelorism.

Sarcoma botryoides of the uterine endocervix: long-term results of conservative surgery.

Sarcoma botryoides, a variant of embryonal rhabdomyosarcoma, is the most common neoplasm of the lower genital tract in girls under 16 years of age. This neoplasm more frequently has a vaginal location in patients younger than 4 years, whereas a cervical location has its peak incidence in the second decade. Although the recommended therapy has been radical surgery alone or combined with other modalities, the use of neoadjuvant chemotherapy has changed the surgical approach to one employing a less radical procedure such as a simple hysterectomy or local excision. We present the case of a 12-year-old girl diagnosed with an embryonal rhabdomyosarcoma of the endocervix who received vincristine-Adriamycin-cyclophosphamide combination chemotherapy followed by a simple hysterectomy. The patient exhibits no evidence of disease 8 years after the initial diagnosis.

Eosinophilic fasciitis--progression to linear scleroderma: a case report.

Eosinophilic fasciitis is a rare disease in children. Although changes similar to linear scleroderma have been reported, the outcome is usually good. In this report, a 10-year-old boy who developed eosinophilic fasciitis without a good response to steroids is presented. He progressed to linear scleroderma within months. Our case reinforces the hypothesis that eosinophilic fasciitis may be an early manifestation or a variant of localized scleroderma similar to the other cases in the literature.

The effect of delivery on umbilical arterial cord blood gases and lipid peroxides: comparison of vaginal delivery and cesarean section.

Umbilical arterial blood gas analysis is the most objective method to assess fetal well being at birth, is the gold standard assessment of uteroplacental function and fetal oxygenation/acid-base status at birth, and it excludes the diagnosis of birth asphyxia in approximately 80% of depressed newborns at term. This study was designed to determine the effect of the type of delivery on umbilical cord blood gases and on free radical activity together with antioxidation in the fetus. Ninety-six pregnant women between 37 and 42 weeks of gestation were included to the study and randomly assigned to the one of three groups: Group 1 (n = 40) were vaginally delivered, Group 2 (n = 26) had cesarean section with epidural anaesthesia, and Group 3 (n = 30) had cesarean section under general anaesthesia. Umbilical artery blood gas analysis was performed just after the delivery of the fetus together with melondealdehyde and glutathione. The umbilical arterial PO2 was found to be higher in Group 3, and malondealdehyde and glutathione levels were lower in newborns of Group 2. It can be concluded that cesarean section with epidural anaesthesia is safer when lipid peroxides are concerned.

The effect of smoking and caffeine on the fetus and placenta in pregnancy.

The aim of this study was to determine the effects of tobacco use and consumption of caffeine in pregnancy on the fetus and placenta by measuring the body weights, head circumferences, and lengths of newborns, and also weights and diameters of placentas. In this prospective study, two main groups were chosen for the study: Group I: A total of 63 pregnant non-smokers; were separated into two subgroups according to their daily caffeine intake; less than 300 mg (Ia) (n = 44), and more than 300 mg (Ib) (n = 19). Group II: 60 pregnant smokers were also separated into two subgroups; daily caffeine intake less than 300 mg (IIa) (n = 43), and more than 300 mg (IIb) (n = 17). The newborns and placentas of both groups were examined. The body weights, lengths, and head circumferences of newborns and also weights and diameters of placentas were measured. The pregnant non-smokers consuming caffeine more than 300 mg/day had statistically significant lower weights of newborns and placentas (p < 0.05). However, there was no significant difference between groups according to the lengths, head circumferences of newborns and diameters of placentas. There were significantly lower body weights of newborns and placentas in pregnant smokers (p < 0.05). There was no difference according to the diameters of placentas, and lengths and head circumferences of newborns in either group. In conclusion, it is suggested that smoking in pregnancy should be prevented both for the health of newborns and mothers, and also caffeine including beverages like tea and coffee should be limited in pregnancy.

The relationship between mitral valve prolapse and acute rheumatic fever in pediatric patients.

Mitral valve prolapse (MVP) is a clinical syndrome of which mitral regurgitation and congestive heart failure are the late sequelae. It can be usually diagnosed by echocardiography. In this study, we reevaluated the patients with acute rheumatic fever (ARF) who were followed-up regularly for aspects of MVP. Physical examination, echocardiography and Doppler study were performed for all the patients. One hundred twenty-seven cases of polyarthritis (54.7%), and 105 cases of valvular involvement (45.3%) were diagnosed. Echocardiography demonstrated MVP in 46.8% with isolated mitral insufficiency, in 38.2% with combined valvular defect and in 12.6% with only polyarthritis. One hundred healthy children comprised the control group. Statistical analyses revealed a significant difference in favor of valvular involvement between the groups.

Adrenomedullin and nitrite levels in children with minimal change nephrotic syndrome.

Nitric oxide (NO) serves many functions within the kidney, and recent evidence suggests that NO contributes to glomerular injury. Adrenomedullin (AM) is a novel hypotensive peptide originally isolated from human pheochromocytoma. Recent studies showed that plasma AM concentrations correlated with the extent of proteinuria. We have examined the possible role of these two agents by studying plasma and urinary total nitrite (NO-2 + NO-3) and AM levels in children with minimal change nephrotic syndrome (MCNS). In comparison with healthy controls, children with MCNS had increased urinary nitrite excretion (micromol/mg urinary creatinine), irrespective of whether the disease was in relapse or remission (3.2+/-0.2 in relapse, n=13; 1.9+/-0.3 in remission, n=12; 1.0+/-0.2 in controls, n=10, P<0.05). Plasma nitrite levels (micromol/l) were high in relapse compared with controls (53.2+/-8.7 vs. 32+/-4.0, P<0.05). Plasma AM levels (pmol/ml) were decreased in relapse (27.6+/-1.4 in relapse, 43.3+/-1.2 in remission, 41.5+/-1.6 in controls, P<0.05). Urinary AM levels (pmol/mg urinary creatinine) were significantly higher in relapse than in remission and in controls (156+/-43 in relapse, 56+/-18 in remission, 36+/-16 in controls, P<0.05). Our data indicate that NO may play a role in mediating the clinical manifestations of MCNS in children. However, changes in AM levels may be the result of heavy proteinuria.

Sympathetic skin response in patients with chronic renal failure.

Sympathetic skin response (SSR) was measured in 20 normal healthy subjects and in 22 patients with chronic renal failure on regular hemodialysis, and its correlation with abnormalities of sensorimotor nerve conduction study and clinical autonomic symptoms was investigated. Nerve conduction studies (NCS) were abnormal in 17 of 22 patients (77.3%), and SSR was absent in 14 of 22 patients (63.6%). Patients were divided into three groups based on their SSR response: patients with normal SSR (n: 8, 36.4%), patients with absent SSR in the foot only (n: 9, 40.9%), and patients with absent SSR in both hand and foot (n: 5, 22.7%). Good correlation between abnormalities of NCS and absent SSR was observed. No correlation was noted between patient age, sex, duration of hemodialysis, duration of renal failure history, and absent SSR. However, statistically significant correlation was found between mean amplitude of the foot SSRs and sensorimotor nerve conduction velocities, and weekly frequency of hemodialysis.

Adrenomedullin and nitrite levels in children with dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is an important cause of chronic congestive cardiac failure in children. In patients with idiopathic DCM, endothelium vasomotor function is disturbed. There are many studies on the roles of nitric oxide (NO) and adrenomedullin (AM) in adult patients with DCM. However, to our knowledge, no studies have investigated the level of AM and NO in children with idiopathic DCM. We determined plasma and urinary AM and total nitrite concentrations in children with idiopathic DCM and investigated the correlation between these and other clinical and laboratory findings. Eleven patients with DCM, ranging in age from 5 month to 14 years, were compared to 10 healthy age- and sex-matched controls. Plasma (pmol/ml) and urinary (pmol/mg creatinine) AM levels were significantly lower than in the healthy controls (19.55 +/- 2.36 vs 51.61 +/- 7.22 and 28.29 +/- 20.66 vs 68.87 +/- 40.23, respectively; p <0.001). Plasma and urinary AM levels were negatively correlated with ejection fraction (EF) and fractional shortening (FS). The plasma (Mmol/L) and urinary nitrite levels (Mmol/mg creatinine) were not different between patients and controls [50.90 +/- 17.50 VS 53.40 +/- 26.05 (P > 0.05) and 1.98 +/- 1.24 vs 2.75 +/- 1.68 (p > 0.05), respectively]. In our study, the first to analyze AM and nitrite levels in children with DCM, plasma and urinary AM levels were found to be decreased. A possible explanation for this reduction could be depletion of the viable myocyte population. However, this hypothesis must be clarified by further studies.

Adrenomedullin and nitrite levels in children with Bartter syndrome.

Children with Bartter syndrome have lower than normal vascular reactivity with normotension in spite of biochemical and hormonal abnormalities which are typical of hypertension. Nitric oxide (NO) is a potent endogenous vasodilator, and plays an important role in the control of vascular tone. Adrenomedullin (AM) is a novel hypotensive peptide originally isolated from human pheochromocytoma. The possible role of NO and AM in maintaining this reduced vascular reactivity was examined by studying plasma and urinary nitrite, a stable metabolite of NO, and AM levels in ten children with Bartter syndrome, ten healthy controls, and five children with hypokalemia of causes other than Bartter syndrome (pseudo-Bartter). Urinary excretion of nitrite (mumol/mg urinary creatinine) was 8.9 +/- 1.2 in children with Bartter syndrome, 4.7 +/- 0.9 in healthy controls, and 2.9 +/- 0.8 in pseudo-Bartter (P < 0.05). Plasma nitrite levels (mumol/l) were 101.9 +/- 23.4, 59.9 +/- 14.7, and 65.0 +/- 29.7, respectively (P < 0.05), in the three groups. Urinary excretion of AM (pmol/mg urinary creatinine) was 187 +/- 40, 65 +/- 10, and 160 +/- 50, respectively (P < 0.05), in the three groups. Plasma AM levels were 47.4 +/- 1.8, 39.9 +/- 5.9, and 42.4 +/- 3.9, respectively (P > 0.05), in the three groups. The same parameters were repeated in the two groups of controls and in the Bartter patients in the 6th month of therapy. Urinary nitrite and AM levels were still higher in the Bartter patients than in the other groups. We conclude that in Bartter syndrome the increased NO production may be responsible for the reduced vascular response of the disease. Initially, increased levels of AM in Bartter syndrome and pseudo-Bartter may be a compensatory response to acute hypokalemia; however, continuation of a high level of urinary excretion of AM in children with Bartter syndrome may suggest also the possible role of AM in the reduced vascular response of the disease.