Proposed Cutoff Level Research Articles

Socioeconomic status is related to pubertal development in a German cohort

INTRODUCTION Current health literature suggests that there has been a decline in the age of pubertal onset and that pubertal onset/duration of puberty may, besides weight status, be influenced by socioeconomic context. OBJECTIVE The goal of this study was to determine whether pubertal onset/duration and puberty-triggering hormones luteinizing hormone (LH) and follicle-stimulating hormone (FSH) vary according to socioeconomic status (SES). Moreover, we aimed to propose cutoff values of serum LH and FSH for predicting gonadarche in boys. METHODS 2,657 apparently healthy children and adolescents between 5.5 and 18 years from the area of Leipzig were recruited from the LIFE Child study. Age at pubertal onset/end of puberty was given in 738/573 children, respectively. Anthropometric parameters of puberty, blood measurements of LH and FSH, and questionnaires assessing SES were evaluated. RESULTS Lower SES was associated with earlier thelarche and longer duration of puberty in overweight/obese girls, whereas age of menarche was not affected. In boys with low SES, a trend versus earlier puberty onset can be seen. Lower SES was significantly associated with boys' age at mutation. No significant differences in boys' and girls' serum levels of LH and FSH during puberty according to SES were observed. Serum LH levels of 0.56 IU/L and serum FSH levels of 1.74 IU/L showed the best prediction of gonadarche in boys. CONCLUSION Puberty onset/duration and boys' age at mutation is affected by SES. The proposed cutoff levels for serum LH and FSH could provide a serological tool to determine gonadarche in boys.

Socioeconomic Status Is Related to Pubertal Development in a German Cohort

Introduction: Current health literature suggests that there has been a decline in the age of pubertal onset and that pubertal onset/duration of puberty may, besides weight status, be influenced by socioeconomic context. Objective: The goal of this study was to determine whether pubertal onset/duration and puberty-triggering hormones luteinizing hormone (LH) and follicle-stimulating hormone (FSH) vary according to socioeconomic status (SES). Moreover, we aimed to propose cutoff values of serum LH and FSH for predicting gonadarche in boys. Methods: 2,657 apparently healthy children and adolescents between 5.5 and 18 years from the area of Leipzig were recruited from the LIFE Child study. Age at pubertal onset/end of puberty was given in 738/573 children, respectively. Anthropometric parameters of puberty, blood measurements of LH and FSH, and questionnaires assessing SES were evaluated. Results: Lower SES was associated with earlier thelarche and longer duration of puberty in overweight/obese girls, whereas age of menarche was not affected. In boys with low SES, a trend versus earlier puberty onset can be seen. Lower SES was significantly associated with boys’ age at mutation. No significant differences in boys’ and girls’ serum levels of LH and FSH during puberty according to SES were observed. Serum LH levels of 0.56 IU/L and serum FSH levels of 1.74 IU/L showed the best prediction of gonadarche in boys. Conclusion: Puberty onset/duration and boys’ age at mutation is affected by SES. The proposed cutoff levels for serum LH and FSH could provide a serological tool to determine gonadarche in boys.

(TIMP2) x (IGFBP7) as early renal biomarker for the prediction of acute kidney injury in aortic surgery (TIGER). A single center observational study.

ObjectivePostoperative acute kidney injury (po-AKI) is frequently observed after major vascular surgery and impacts on mortality rates. Early identification of po-AKI patients using the novel urinary biomarkers insulin-like growth factor-binding-protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) might help in early identification of individuals at risk of AKI and enable timely introduction of preventative or therapeutic interventions with the aim of reducing the incidence of po-AKI. We investigated whether biomarker-based monitoring would allow for early detection of po-AKI in patients undergoing abdominal aortic interventions.MethodsIn an investigator-initiated prospective single-center observational study in a tertiary care academic center, adult patients with emergency/ elective abdominal aortic repair were included. Patients were tested for concentrations of urinary (TIMP-2) x (IGFBP7) at baseline, after surgical interventions (PO), and in the mornings of the first postoperative day (POD1). The primary endpoint was a difference in urinary (TIMP-2) x (IGFBP7) levels at POD1 in patients with/ without po-AKI (all KDIGO stages, po-AKI until seven days after surgery). Secondary endpoints included sensitivity/ specificity analyses of previously proposed cut-off levels and clinical outcome measures (e.g. need for renal replacement therapy).Results93 patients (n = 71 open surgery) were included. Po-AKI was observed in 33% (31/93) of patients. Urinary (TIMP-2) x (IGFBP7) levels at POD1 did not differ between patients with/ without AKI (median 0.39, interquartile range [IQR] 0.13–1.05 and median 0.23, IQR 0.14–0.53, p = .11, respectively) and PO (median 0.2, IQR 0.08–0.42, 0.18, IQR 0.09–0.46; p = .79). Higher median (TIMP-2) x (IGFBP7) levels were noted in KDIGO stage 3 pAKI patients at POD1 (3.75, IQR 1.97–6.92; p = .003). Previously proposed cutoff levels (0.3, 2) showed moderate sensitivity/ specificity (0.58/0.58 and 0.16/0.98, respectively).ConclusionIn a prospective monocentric observational study in patients after abdominal aortic repair, early assessment of urinary (TIMP-2) x (IGFBP7) did not appear to have adequate sensitivity/ specificity to identify patients that later developed postoperative AKI.Clinicaltrials.govNCT03469765, registered March 19, 2018.

30-Minute Delta Cortisol Post-ACTH Stimulation Test and Proposed Cut-Off Levels for Adrenal Insufficiency Diagnosis.

The ACTH stimulation test is used to diagnose adrenal insufficiency (AI). This study evaluated the diagnostic performance of serum delta cortisol from ACTH stimulation tests and determined appropriate cut-off levels of serum 30-minute delta cortisol for the diagnosis of AI, allowing a reduction in the number of 60-minute cortisol tests. A 6-year retrospective study in 471 patients was conducted. The performance of the serum delta cortisol in diagnosing AI was assessd using a multivariable logistic regression model and the area under ROC curves (AuROC). Both serum 30-minute and 60-minute delta cortisol demonstrated equally high diagnostic accuracy for AI (AuROC for LDT : 0.91 vs 0.90 ; HDT : 0.91 vs 0.92, respectively). The 30-minute delta cortisol test was chosen to develop proposed diagnostic cut-off levels due to its simplicity. The proposed lower cut-off level for 30-minute delta cortisol was Δ < 1.8 µg/dL for both LDT and HDT. The upper cut-off levels were Δ > 11.8 µg/dL for LDT and Δ > 10.5 µg/dL for HDT. These cut-off levels yielded high sensitivity and specificity > 90%. The 30-minute serum delta cortisol using the proposed cut-off levels provides diagnostic performance for AI equal to that of the 60-minute test and is more convenient, requires less time, less invasive and is cost-saving. 67 : 95-101, February, 2020.

Vibrio profundi sp. nov., isolated from a deep-sea seamount.

A Gram-stain negative, rod-shaped, facultative anaerobic, motile bacterial strain, designated TP187T, was isolated from a seamount near the Yap Trench in the tropical western Pacific. Phylogenetic analysis based on the 16S rRNA gene sequence showed that strain TP187T is related to members of the genus Vibrio and has high 16S rRNA gene sequence similarity with the type strains of Vibrio chagasii (97.3%) and Vibrio gallaecicus (97.1%). Sequence similarities to all other type strains of current species of the genus Vibrio were below 97%. The polar lipids profile was found to contain diphosphatidylglycerol, phosphatidylglycerol, an aminophospholipid, two aminolipids, four phospholipids and eleven unidentified polar lipids. Ubiquinone Q-8 was detected as the predominant quinone. The genomic DNA G + C content of strain TP187T was determined to be 43.7mol%. In addition, the maximum values of in silico DNA-DNA hybridization (isDDH) and average nucleotide identity (ANI) between strain TP187T with V. chagasii LMG 21353T were 22.40 and 77.50% respectively. Both values are below the proposed cutoff levels for species delineation, i.e. 70 and 95%, respectively. Combined data from phenotypic, phylogenetic, isDDH and ANI data demonstrated that the strain TP187T is representative of a novel species of the genus Vibrio, for which we propose the name Vibrio profundi sp. nov. (type strain TP187T = KACC 18555T = CGMCC 1.15395T).

Evaluation of Liver Graft Recipient Workup in Predicting of Early Cardiovascular Events During Liver Transplantation: A Single-Center Experience

BackgroundCardiovascular events (CVE) contribute to serious complications and death after liver transplantation (LT). Troponin I (TnI) level >0.07 mg/L and prior cardiac disease are known to be the independent predictors for posttransplant CVE. We evaluated single-center cardiac workup to predict early cardiovascular morbidity and mortality after LT. Patients and methodsWe recruited 105 consecutive liver transplant recipients (male/female, 59/46; mean age, 51.66 ± 11.67 years). The cardiological assessment at evaluation for LT included medical history, electrocardiogram, echocardiography, Holter monitoring, and exercise test. We collected data regarding CVE including hypotonia with catecholamine usage, arrhythmia, sudden cardiac death, pulmonary edema, and myocardial infarction within 7 days after LT. ResultsCVE during LT occurred in 42 recipients (40%) and after LT in 9 patients (8.57%). Proposed cutoff level of TnI >0.07 mg/L did not correlate with CVE during operation (P = .73) or after LT (P = .47). CVE during LT was associated with arterial hypertension in medical history (P <.001), right ventricular systolic pressure (P< .05), and clinical scores: Child-Pugh (P = .04), Model for End-Stage Liver Disease (MELD) (P = .04), MELD incorporating serum sodium (P<.03), and integrated MELD score (P = .01). CVE after LT correlated only with arrhythmia (P<.001) and catecholamine usage (P < .05) perioperatively. Of interest, catecholamine usage during LT was associated with prolonged stay at the intensive care unit (P < .05). ConclusionThe single-center algorithm with noninvasive cardiac procedures without TnI assessment is optimal in evaluation before LT; however, medical history and severity of the liver disease are crucial for short-term cardiovascular morbidity after LT.

Vibrio fujianensis sp. nov., isolated from aquaculture water

A Gram-stain-negative, facultatively anaerobic strain, designated FJ201301T, was isolated from aquaculture water collected from Fujian province, China. Phylogenetic analysis of 16S rRNA gene sequences indicated that strain FJ201301T belonged to the genus Vibrio, formed a distinct cluster with Vibriocincinnatiensis ATCC 35912T and shared the highest similarity with Vibriosalilacus CGMCC 1.12427T. A 15 bp insertion found in the 16S rRNA gene was a significant marker that distinguished strain FJ201301T from several phylogenetic neighbours (e.g. V. cincinnatiensis). Multilocus sequence analysis of eight genes (ftsZ, gapA, gyrB, mreB, pyrH, recA, rpoA and topA; concatenated 4135 bp sequence) showed that, forming a long and independent phylogenetic branch, strain FJ201301T clustered with V. cincinnatiensis ATCC 35912T, Vibrioinjenensis KCTC 32233T and Vibriometschnikovii CIP 69.14T clearly separated from V. salilacus CGMCC 1.12427T. Furthermore, the highest in silico DNA-DNA hybridization and average nucleotide identity values between strain FJ201301T and the closest related species were 26.3 and 83.1 % with V. cincinnatiensis ATCC 35912T, less than the proposed cutoff levels for species delineation, i.e. 70 and 95 %, respectively. Biochemical, sequence and genomic analysis suggested the designation of strain FJ201301T representing a novel species of the genus Vibrio, for which the name Vibrio fujianensis sp. nov. is proposed. The type strain is FJ201301T (=DSM 104687T=CGMCC 1.16099T).

Proteus columbae sp. nov., isolated from a pigeon in Ma'anshan, China.

A Gram-negative, facultatively anaerobic bacillus, strain 08MAS2615T, was isolated from the flesh of a pigeon specimen collected in Ma'anshan, Anhui province, China. Phylogenetic analysis of 16S rRNA gene sequences confirmed that strain 08MAS2615T belonged to the genus Proteus, and formed an independent branch which was clearly separated from the other six known species of Proteus. Strain 08MAS2615T was more closely related to Proteus vulgaris ATCC 29905T and Proteus penneri NCTC 12737T than other Proteus species. Similar independent phylogenetic results were obtained using rpoB gene sequence analysis, whereas strain 08MAS2615T clustered near the species of Proteus cibarius JS9T and Proteus terrae N5/687T. Furthermore, the genome-wide core-single nucleotide polymorphism-based phylogenetic tree confirmed that strain 08MAS2615T formed a monophyletic and robust clade. Based on whole-genome sequences, the range of in silico DNA-DNA hybridization and average nucleotide identity between strain 08MAS2615T and the six Proteus species were 25.5-48.8 % and 82.8-92.9 %, respectively, less than the proposed cutoff level for species delineation, i.e. 70 and 95 %. In addition, the major cellular fatty acid profile of strain 08MAS2615T was C14 : 0 (12.4 %), C16 : 0 (23.8 %), C17 : 0cyclo (14.4 %), summed feature 2 (C16 : 1iso I/C14 : 0 3-OH) (11.0 %), summed feature 3 (C16 : 1ω7c/16 : 1ω6c) (18.5 %) and summed feature 8 (C18 : 1ω6c) (18.6 %). On the basis of these results, strain 08MAS2615T represents a novel species of the genus Proteus, for which the name Proteuscolumbae sp. nov. is proposed with strain 08MAS2615T (=DSM 104686T=CGMCC 1.15982T) designated as the species type strain.

Risperidone and Venlafaxine Metabolic Ratios Strongly Predict a CYP2D6 Poor Metabolizing Genotype.

To investigate the predictive value of the risperidone and venlafaxine metabolic ratios and CYP2D6 genotype. The determination of risperidone, 9-hydroxyrisperidone, and venlafaxine, O-desmethylvenlafaxine, N-desmethylvenlafaxine and CYP2D6 genotype was performed in 425 and 491 patients, respectively. The receiver operator characteristic method and the area under the receiver operator characteristic curve were used to illustrate the predictive value of risperidone metabolic ratio for the individual CYP2D6 genotype. To evaluate the proposed cutoff levels of >1 to identify individuals with a poor CYP2D6 genotype, the sensitivity, specificity, positive predictive values, and negative predictive values were calculated. Area under the receiver operator characteristic curve to predict poor metabolizers for risperidone/9-hydroxyrisperidone and N-desmethylvenlafaxine/O-desmethylvenlafaxine ratios was 93% and 99%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value (confidence interval) of a risperidone/9-hydroxyrisperidone ratio >1 to predict a CYP2D6 poor metabolizer genotype were 91% (76%-97%), 86% (83%-89%), 35% (26%-46%), and 99% (97%-100%), respectively. The corresponding measures for N-desmethylvenlafaxine/O-desmethylvenlafaxine were 93% (76%-97%), 87% (83%-89%), 40% (32%-51%), and 99% (98%-100%). Risperidone/9-hydroxyrisperidone and N-desmethylvenlafaxine/O-desmethylvenlafaxine metabolic ratios >1 strongly predict individuals with poor metabolizer genotype, which could guide psychotropic drug treatment to avoid adverse drug reactions and to increase their therapeutic efficacy in patients prescribed these drugs.

Performance of waist circumference and proposed cutoff levels for defining overweight and obesity in Nigerians

Background:Waist circumference (WC) is a simple tool for measuring central obesity in routine clinic settings. Gender- and ethnic-specific optimal cutoff points for WC are encouraged for populations lacking such data.Objectives:To derive WC cutoff values, predictive of overweight and obesity in Nigerians and to evaluate the performance of currently recommended values.Subjects and Methods:Apparently, healthy urban dwellers from six cities spread across Nigeria were selected for this cross-sectional study. Biophysical profiles such as blood pressure and anthropometric indices were measured according to the World Health Organization's STEPs instrument protocol. Receiver operating characteristics curve analysis was used to determine the optimal cutoff levels using the decision rule of maximum (sensitivity + specificity). The level of significance was set at P < 0.05.Results:A total of 6089 subjects (3234 males and 2855 females) were recruited for the study. WC demonstrated a high area under the curve in both genders. Selected cutoff points ranged from 83 to 96 cm with high sensitivities and specificities.Conclusions:The currently recommended gender-specific WC cutoff values proved inappropriate in this study group, but WC remains a reliable tool for measuring obesity.

Risperidone metabolic ratio as a biomarker of individual CYP2D6 genotype in schizophrenic patients

The purpose of the present study was to investigate the predictive value of the risperidone metabolic ratio for the individual CYP2D6 genotype. The determination of risperidone, 9-hydroxyrisperidone, and CYP2D6 genotype was performed in 89 schizophrenic patients. The receiver operator characteristic (ROC) method and the area under the ROC curve (AUC) were used to illustrate the predictive value of risperidone metabolic ratio for the individual CYP2D6 genotype. The area under the ROC curve (AUC) was used as a global measure of this predictive value. To evaluate the proposed cutoff levels of >1 and <0.1 to identify individuals with a poor or ultrarapid CYP2D6 genotype the sensitivity, specificity, positive predictive value and negative predictive were calculated. The area under the ROC curve (AUC) for poor and ultrarapid metabolisers was 0.85 and 0.86, respectively. The sensitivity, specificity, positive predictive value and negative predictive value of a risperidone/9-OH-risperidone ratio >1 to CYP2D6 poor metaboliser genotype were 75 %, 95 %, 60 % and 97 %, respectively. The corresponding measures for a metabolic ratio < 0.1 to predict ultrarapid metabolisers were 80 %, 77 %, 18 % and 98 %. A metabolic ratio > 1 or < 0.1 may be a useful therapeutic biomarker to recommend CYP2D6 genetic testing to guide the present or future treatment of patients in need of psychotropic drugs.

The Value of Specific IgE to Peanut and Its Component Ara h 2 in the Diagnosis of Peanut Allergy

To avoid unnecessary oral food challenges, which are time consuming, stressful, and risky, improved in vitro diagnostic methods for food allergy such as component resolved diagnostics are still under investigation. To investigate the role of whole peanut- and peanut-component (Ara h 1, Ara h 2, Ara h 3, Ara h 6 and Ara h8)-specific IgE levels in the diagnostic procedure of peanut allergy as well as the diagnostic properties of peanut-specific IgG and IgG4. Sixty-one children underwent oral peanut challenge tests for diagnostic purposes irrespective of their peanut-specific IgE levels. Peanut-specific serum IgE, IgG, and IgG4 levels were determined by ImmunoCAP FEIA and specific IgE against individual peanut proteins by Immuno Solid-phase Allergen Chip. Thirty-four of 61 patients (56%) had a peanut allergy. No significant difference was observed for peanut-specific IgG or peanut-specific IgG4 levels between patients who were allergic and tolerant patients, whereas peanut-specific IgE was significant higher in patients who were allergic than in tolerant patients (P < .005). Twenty-five of 61 children had peanut-specific IgE above a previously proposed cutoff level of 15 kUA/L; however, 7 of these 25 children (28%) were clinically tolerant. Ara h 2-specific IgE was significantly lower in tolerant than in patients with allergies (P < .0001). Interestingly, 94% of the patients with peanut allergies showed IgE-binding to Ara h 2. Unfortunately, 26% of the sensitized but tolerant patients have shown IgE binding to Ara h 2 too. Neither the level of specific IgE to peanut nor to Ara h 2 was able to clearly distinguish patients with clinical relevant peanut allergy from those who were clinical tolerant in our population. As expected, peanut-specific IgG and IgG4 did not improve the diagnostic procedure.

Proposed cutoff level of waist circumference in Japanese men: evaluation by homeostasis model assessment of insulin resistance levels.

The aim of this study is to propose the cutoff level of waist circumference (WC) on the basis of homeostasis model assessment of insulin resistance (HOMA-IR) levels in order to diagnose metabolic syndrome (MetS). We examined a total of 798 non-diabetic men (40-65 years of age) by using a receiver operating characteristic (ROC) curve to determine the cutoff level that yielded the maximum sensitivity plus specificity. According to the criteria proposed by the International Diabetes Federation (IDF), and the Japanese Society of Internal Medicine (JSIM), subjects with ≥ 2 metabolic components other than abdominal obesity, were considered to have MetS. The overall prevalence rates of IDF- and JSIM-MetS were 17.4% (n=139) and 15.5% (n=124), respectively. The median levels of WC and HOMA-IR were 83.1 [interquartile range (IQR): 78.5-88.4] cm and 0.84 (IQR: 0.61-1.19), respectively. HOMA-IR was highly correlated with each metabolic parameter (each p<0.05), and in addition, multiple linear regression analysis of HOMA-IR (adjusted R2=0.459) showed that WC level was the strongest independent predictors of HOMA-IR level (F=141.1, p<0.05). According to ROC curve analysis, the cutoff level of HOMA-IR for predicting IDF- and JSIM-MetS was 0.92 for both (sensitivity: 79.9% and 78.2%, specificity: 64.9% and 63.6%). Based on the HOMA-IR level, the proposed WC cutoff level was 82.7 cm (sensitivity: 75.4%, specificity: 63.8%). This study suggests that WC level should be more strictly managed than current criteria, for preventing the development of MetS in non-diabetic middle-aged Japanese men.

ORAL PRESENTATION

ORAL PRESENTATION

Estructura factorial y propiedades psicométricas de una escala de depresión en universitarios de Colombia

To determine the psychometric properties and factor structure of the Center for Epidemiological Studies depression scale (CES-D) with a sample of Colombian university students. A non-probabilistic convenience sample of 355 students from two universities (62% women and 38% men) were selected according to quotas from the educational institutions, a random sample of groups, and volunteer participants. The Spanish version of the CES-D was modified by extending the evaluation period to two weeks. The total score was calculated for each scale and factor; the exploratory factor analysis was conducted using the method of principal components. The four factors: depressive affect, somatic symptoms, positive affect, and interpersonal relations, accounted for 55.9% of the variance. The analysis showed high levels of internal consistency (Cronbach's alpha = 0.88). The individual factors showed variations in internal consistency and converged around a single, secondary factor. The factor structure matched the original theory, even with variations in the factor structure for the whole sample, as well as by gender. Although scores differed according to the sex of the person being evaluated, the internal consistency of the scale as a whole remained over 0.87 for each sex. The proposed cutoff levels for the test were: 39 points for the general population, 35 for males, and 42 for females, all above the fourth quintile. The CES-D scale has satisfactory psychometric properties and can be recommended for use in university students. These results lend themselves to the possibility of using this scale in both clinical and epidemiological studies.

C-reactive protein and echocardiography have little impact on risk stratification in never-treated hypertensive patients

The aim of this study was to assess the contribution of increased concentrations of high-sensitivity C-reactive protein (hsCRP) and echocardiography to risk stratification according to the 2003 European guidelines for the management of arterial hypertension in patients with untreated hypertension. A total of 207 consecutive medical outpatients with untreated hypertension were included. History and clinical examination, electrocardiography, laboratory analyses including the measurement of hsCRP and echocardiography were performed in all patients. Patients were classified into four risk groups with and without using echocardiography and hsCRP concentrations of at least 10 mg/l according to the 2003 guidelines for the management of hypertension. The majority of the 207 patients (81%) were at moderate or high cardiovascular risk before adding echocardiography and/or hsCRP to the risk stratification process. When echocardiography was included, only three patients were reclassified from the moderate added risk to the high added risk group. Adding hsCRP concentrations of at least 10 mg/l had no impact on risk stratification. Using an hsCRP cutoff level of 3 mg/l, one patient was at moderate instead of low added risk, eight patients were at high instead of moderate added risk and one patient was at very high instead of high added risk. We conclude that hsCRP at the proposed cutoff level of 10 mg/l has no impact on risk stratification in outpatients with untreated hypertension. An hsCRP cutoff level of 3 mg/l may be more suitable for risk stratification. Finally, our data suggest that depending on the population studied, there is minimal impact of echocardiography on risk stratification.

Rastreamento Antenatal da Síndrome de Down Utilizando Parâmetros Ultra-sonográficos

Purpose: to appraise the value of ultrasonographic parameters for the diagnosis of fetal Down syndrome (T21), in order to permit its use in routine clinical practice. Methods: this is a prospective cohort study using various ultrasonographic parameters for the prediction of T21. A total of 1662 scans were evaluated in the cohort study and 289 examinations were analyzed as a differential sample to test the normality curve from October 1993 to November 2000. The statistical analysis was based on the calculation of intra- and interobserver variations, the construction of normality curves for the studied parameters, as well as their validity tests, and the calculation of sensitivity, specificity, relative risk, likelyhood ratio and posttest predictive values. Results: among 1662 cases, 22 fetuses (1.32%) with T21 were identified. The normality curves were built for nucal fold thickness, femur/foot ratio and nasal bone length. Renal pelvis had a semiquantitative distribution and the proposed cutoff level was 4.0 mm. Sensitivity, specificity, false positive rate, relative risk and likelyhood ratio for nucal fold measurements above the 95th percentile were 54.5%, 95.2%, 4.9%, 20.2 and 11, respectively. For nasal bone measurements below the 5th percentile, 59.0%, 90.1%, 9.0%, 13.4 and 6.5. For femur/foot ratio below the 5th percentile, 45.5%, 84.4%, 15.6%, 3.7 and 2,6. For renal pelvis greater than 4.0 mm, 36.4%, 89.2%, 10.9%, 4.5 and 3.4. For absent fifth finger middle phalanx, 22.7%, 98.1%, 1.9%, 13.2 and 11.9. For the presence of major malformations, 31.8%, 98.7%, 1.3%, 27.2 and 24,8. After calculating the probability rates and the incidence of T21 in different maternal ages, a table for posttest risk using ultrasonographic parameters was set up. Conclusions: normality curves and indices for the assessment of risk for fetal Down syndrome on a population basis were established by the utilization of different maternal ages and by multiplying factors proposed by the authors. It was not possible to establish a normality curve for renal pelvis measurements, because of their semiquantitative distribution.

Impact of cyclosporin A pharmacokinetics on the presence of side effects in pediatric renal transplantation.

Cyclosporin A (CsA) is a potent immunosuppressant that has many side effects, including hypertrichosis, gingival hyperplasia, and tremor. To evaluate whether there is a relationship between the CsA-pharmacokinetics (PK) and these side effects, their presence and intensity were observed in 46 renal transplanted children/adolescents during two regular visits, and the occurrence of the side effects was correlated with CsA-PK. CsA doses had been unchanged for at least 6 mo. CsA blood concentrations were measured at time 0, and 1, 2, and 4 h after the CsA morning dose. An abbreviated area under the curve (AUC) was calculated using C0, C2, and C4. Hypertrichosis positively correlated with C2, C4, Cmax, and AUC. An AUC > or = 4158 ng/ml per h was the best predictor for the presence of hypertrichosis. Tremor was also positively correlated with C2, Cmax, and AUC. A Cmax > or = 878 ng/ml was the best predictor for the appearance of tremor. These values of Cmax and AUC are within the therapeutic range of CsA as demonstrated by the studies of calcineurin inhibition by CsA. Gingival hyperplasia was not associated with any of the CsA-PK studied parameters. However, it was associated with the concomitant use of nifedipine. These data show that there is a correlation between the CsA side effects and its pharmacokinetics and that it is possible to decrease the incidence and intensity of such side effects by monitoring the CsA-PK parameters, providing they are under or at the proposed cutoff levels. Nifedipine should also be avoided to reduce the presence of gingival hyperplasia.