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Biomedical subjects

A Herman

Publications and source records attributed to A Herman.

At least 37 records · Page 2Linked to original sources

RenaGel efficacy in severe secondary hyperparathyroidism.

BACKGROUND: Haemodialysis patients frequently have simultaneous hypercalcemia and hyperphosphatemia, posing a therapeutic dilemma for the traditional calcium--and aluminum--based binders. RenaGel (sevelamer hydrochloride) is an effective phosphate binder without changes in serum calcium or aluminum levels. However being an expensive medication it is currently used mainly for patients with moderate to severe secondary hyperparathyroidism. However most of the previous studies have not included patients with severe secondary hyperparathyroidism. METHODS: Our purpose is to determine RenaGel binder efficacy in haemodialysis patients with severe secondary hyperparathyroidism. As a secondary purpose we have followed the variations of parathyroid hormone, serum calcium, serum lipids [low- and high-density lipoprotein cholesterol, triglycerides and Lipoprotein(a)], uric acid and bicarbonate. All phosphate binders previously used were suspended one week before RenaGel prescription. Our study included 18 adult haemodialysis patients, with PTHi of 810 +/- 330 pg/ml after the "pre-treatment" washout. The binder was administered during 12 weeks, beginning with a mean dose of 2.4 +/- 0.4 g daily and adjusted to obtain serum phosphorus under 6.5 mg/dl (at the end of the study, the mean RenaGel dose was 2.8 +/- 0.6 g daily. RESULTS: The mean changes after RenaGel in serum phosphorus was -0.7 +/- 1.5. mg/dl (P < 0.05), in serum calcium was 0.5 +/- 1.0 mg/dl (P < 0.05) and in calcium x phosphate product of -4.0 +/- 12.4 mg/dl (P = NS). "Post-treatment" the PTHi levels remained stable (820 +/- 360 pg/ml vs 810 +/- 330) but serum alkaline phosphatase increased (14.3 +/- 14.4 U/l; P < 0.01). LDL cholesterol serum levels decreased by -35 +/- 10 mg/dl (P < 0.01), HDL cholesterol showed a trend to increase (3.0 +/- 8.1 U/l; P = NS), triglycerides decreased by 38 +/- 56 mg/dl (P < 0.05) and Lipoprotein(a) remained stable. Serum albumin increased by 0.1 +/- 0.2 g/L (P < 0.05), uric acid decreased -0.8 +/- 1.2 mg/dl (P < 0.05) and bicarbonate remained unchanged. CONCLUSIONS: RenaGel is an effective phosphate binder, even in haemodialysis patients with severe secondary hyperparathyroidism. The lipid profile improved with the treatment, with the exception of Lipoprotein(a) stabilization. Selection of patients with severe secondary hyperparathyroidism at the beginning of RenaGel disposal, for economic reasons is debatable, but could be correct.

Adult↗

Circular dichroism spectra of the achiral guest N-aryl-N-nitrosamines included in the crystal host matrices of cholic acid.

The crystalline inclusion complexes of cholic acid with three symmetric N-aryl-N-nitrosamines were prepared, and their X-ray structures were solved. As a result of chiral conformations adopted by the enclathrated guest nitrosamines, the solid-state CD spectra were measured in KBr disks. The observed Cotton effect sign, corresponding to the n-pi* transition, was correlated with the helicity of the twisted nitrosamine chromophore conjugated with the N-aryl substituent. In addition, the absolute configuration of the enantiomorphous crystals of N-benzyl-N-nitroso-4-chloroaniline was established on the basis of the solid-state CD and X-ray crystallographic results.

Carcinogens↗

Identification and modulation of a naturally processed T cell epitope from the diabetes-associated autoantigen human glutamic acid decarboxylase 65 (hGAD65).

T cell recognition of autoantigens is critical to progressive immune-mediated destruction of islet cells, which leads to autoimmune diabetes. We identified a naturally presented autoantigen from the human islet antigen glutamic acid decarboxylase, 65-kDa isoform (GAD65), by using a combination of chromatography and mass spectrometry of peptides bound by the type I diabetes (insulin-dependent diabetes mellitus, IDDM)-associated HLA-DR4 molecule. Peptides encompassing this epitope-stimulated GAD65-specific T cells from diabetic patients and a DR4-positive individual at high risk for developing IDDM. T cell responses were antagonized by altered peptide ligands containing single amino acid modifications. This direct identification and manipulation of GAD65 epitope recognition provides an approach toward dissection of the complex CD4(+) T cell response in IDDM.

Adolescent↗

Antenatal sonographic findings of right pulmonary agenesis with ipsilateral microtia: a possible new laterality association.

Right pulmonary agenesis is a rare congenital malformation which results in secondary dextrocardia in situs solitus. Ipsilateral microtia in this context composes a laterality syndrome. The prenatal sonographic findings of this abnormality have not been previously reported. We describe the association of dextrocardia in situs solitus, intact diaphragm and right microtia. This was sonographically diagnosed at mid-gestation in an euploid fetus. Surgical evacuation of the pregnancy confirmed the external malformation. Laterality association should be assessed in a fetus with sonographic findings of pulmonary agenesis. The differential diagnosis and updated literature review is presented.

Adult↗

Maternal serum human chorionic gonadotrophin levels in systemic lupus erythematosus and antiphospholipid syndrome.

Maternal serum human chorionic gonadotrophin (hCG) levels were measured during the second and the third trimesters of pregnancy in patients with either systemic lupus erythematosus (SLE) or primary antiphospholipid syndrome (APS). All results were expressed in multiples of the gestation-specific normal medians (MoM). The median MoM level in 17 samples from SLE patients was 1.48 compared with 0.79 MoM in 99 controls of similar gestation (p < 0.002, Wilcoxon Rank sum test). In contrast the median MoM level in 19 samples from primary APS patients was only 1.14. These preliminary findings should be further studied to evaluate the implications for Down syndrome screening, detection of SLE cases during pregnancy and the prediction of adverse outcome in SLE gestations.

Antiphospholipid Syndrome↗

Evidence for digenic inheritance in a family with both febrile convulsions and temporal lobe epilepsy implicating chromosomes 18qter and 1q25-q31.

We report a clinical and genetic study of a French family among whom febrile convulsions (FC) are associated with subsequent temporal lobe epilepsy (TLE) in the same individual, without magnetic resonance imaging-identifiable hippocampal abnormalities. Linkage analyses excluded the loci FEB1 and FEB2, previously implicated in FC; the GEFS+1 locus responsible for generalized epilepsy with febrile seizures plus; and the locus implicated in lateral temporal lobe epilepsy. After scanning the entire genome, significant lod scores (>3) for markers on 18qter and suggestive lod scores (>2) for markers on 1q25-q31 were obtained. An analysis of the haplotypes at these two loci supported the hypothesis that two genes segregated with the phenotype. All patients shared common haplotypes for both 1q25-q31 and 18qter chromosomes. All but one unaffected at-risk individuals carried only one, or none, of the disease haplotypes. Under the assumption of digenic inheritance, haplotype reconstruction defined a 26 cM interval on chromosome 1 and a 10 cM interval on chromosome 18. This family suggests that the association between FC and TLE may be observed in the absence of hippocampal structural abnormalities and that they may have, in some cases, a common genetic basis.

Adolescent↗

Does a 'notched' nuchal translucency indicate Down syndrome fetuses or other adverse pregnancy outcome?

The aim of the present study was to assess the sonographic contour of the increased nuchal translucency (NT) and to correlate this with pregnancy outcome. Fifty sonographic images of fetuses with increased NT [> 95th centile thickness of the normal range for crown-rump length (CRL) between 38 and 84 mm] were retrospectively assessed. In all the cases a complete pregnancy and even infancy follow-up (< 36 months) was available. The NT appearances were subdivided into two forms: a 'notched' or 'uniform' appearance. The images were correlated with karyotype results [trisomy 21 (DS) vs euploid cases] and pregnancy outcome. Complicated outcomes were classified as being either DS fetuses, miscarriage or termination of pregnancy because of structural anomaly. Thus 30/35 (86%) of the euploid fetuses had a 'uniformly' increased NT, whereas 8/13 DS cases (62%) had a 'notched' appearance (Fisher's exact test, p = 0.004). Additionally, 27/29 fetuses (93%) which had an uneventful pregnancy outcome had a 'uniform' increased NT, whereas 12/26 (57%) of the fetuses which had adverse pregnancy outcome had a 'notched' appearance of their NT (Fisher's exact test, p < 0.001). Although it was not possible to correlate the sonographic data with post-evacuation microdissection findings, it is possible that a uniformly shaped, increased NT may be more representative of a developmental delay in a normal fetus. Conversely, a 'notched' nuchal surface may represent abnormal lymphatic or cardiovascular development more commonly seen in DS fetuses.

Adult↗

Large-scale preparation of recombinant ovine prolactin and determination of its in vitro and in vivo activity.

Recombinant bovine Ala-prolactin (PRL) (GenBank Accession No. V00112) in prokaryotic expression plasmid pMON3401 was mutated using a mutagenesis kit, to prepare plasmid encoding ovine PRL (oPRL) (GenBank Accession No. M27057) Escherichia coli cells transformed with this latter plasmid overexpressed large amounts of oPRL upon induction with nalidixic acid. The expressed protein, found in inclusion bodies, was refolded and purified to homogeneity on a Q-Sepharose column, yielding an electrophoretically pure fraction composed of over 98% monomeric protein of the expected molecular mass of approximately 23 kDa. The biological activity of the recombinant oPRL after proper renaturation was evidenced in vitro by its ability to stimulate proliferation of rat lymphoma Nb(2) cells possessing PRL receptors, to stimulate luciferase activity in HEK 293 cells transiently transfected with oPRL receptors, and to induce progesterone secretion in primary cultures of luteal cells obtained from midpregnant ewes. In contrast to ovine growth hormone or ovine placental lactogen, recombinant oPRL had no galactopoietic effect in lactating ewes.

Animals↗

Extensive spinal epidural hematoma: a rare complication of aortic coarctation.

Development of collateral circulation belongs among the typical signs of aortic coarctation. Cerebral or spinal artery aneurysm formation with increased risk of subarachnoid hemorrhage represent the most common neurovascular complication of this disease. We report a case of a 20-year-old sportsman who developed acute non-traumatic paraplegia as a result of extensive spinal epidural hemorrhage from collateral vessels accompanying aortic coarctation which was unrecognized up to that time. To the best of our knowledge, acute spinal epidural hematoma as a complication of aortic coarctation has not been previously reported.

Adult↗

Assessment of access blood flow after preemptive angioplasty.

In an effort to prolong the life of synthetic grafts used for hemodialysis access, current recommendations suggest regular monitoring of vascular access by means of measurements of access blood flows (ABFs) and/or pressures and prompt referral for prophylactic angiography with angioplasty when appropriate. Previous data suggested that angioplasty transiently reduces venous pressure, but repeated angioplasty is often required. Few data exist on the effect of angioplasty on ABF, especially the durability of the response. In this study, we report our experience with 49 consecutive angioplasties of 32 synthetic polytetrafluoroethylene grafts in which ABF was measured serially preangiography and postangiography using the Transonic hemodialysis monitor (Transonic Inc, Ithaca, NY). The primary indication for angiography was a low graft ABF rate (<600 mL/min). Although the most common site for stenosis was the venous anastomosis, the majority of grafts had multiple lesions requiring angioplasty. Mean ABF rate increased from 596 +/- 41 to 922 +/- 48 mL/min postangiography, an increase of almost twofold. This level of blood flow was maintained for the first month, but thereafter ABF began to decrease, reaching 672 +/- 70 mL/min at 3 months and 658 +/- 93 mL/min at 6 months. Two patients were lost to follow-up (one patient died, one patient received a transplant) and 2 grafts were electively ligated. The remaining 28 grafts were followed up for at least 6 months. Four grafts clotted within 3 months of angioplasty and were lost. Nine additional grafts required a second intervention (surgical revision, 2 grafts; repeated angioplasty, 7 grafts) within 6 months, either for a poor initial response to angioplasty or recurrent stenosis. Two of these 9 grafts subsequently clotted and were lost. In all, 22 of the 28 grafts remained patent at 6 months postangioplasty, and 15 grafts were maintaining an ABF greater than 600 mL/min without reintervention at 6 months. In summary, this study indicates that preemptive angioplasty of graft stenoses results in an initial doubling of ABF, but the effect is temporary, with the average ABF decreasing to baseline values by 3 months. Approximately half the grafts required reintervention for either thrombosis or recurrent low flow. However, sustained responses with ABF maintained at greater than 600 mL/min were achieved in the other half.

Angiography↗

The effects of maternal and fetal parameters on the quality of nuchal translucency measurement.

OBJECTIVE: To evaluate the influence of maternal and fetal parameters on the quality of fetal nuchal translucency measurement. DESIGN: This was a prospective study in 227 consecutive pregnant women undergoing nuchal translucency screening by transabdominal sonography. The same well-qualified sonographer performed all the scans and in each case the best-quality image was selected and scored according to an image scoring system (total maximum score, 9). The quality of the image was examined in relation to maternal age, weight, abdominal wall thickness, amniotic sac diameter, posterior uterine wall depth (distance between abdominal wall surface and posterior uterine wall surface), placental location, fetal crown-rump length and nuchal translucency thickness. Correlation coefficients were calculated and stepwise linear regression was used to adjust for confounders and to define the predictors for image score. RESULTS: The only two parameters that provided a significant independent contribution to the prediction of the image score were posterior uterine wall depth and fetal crown-rump length. Intravariable analysis of these two parameters demonstrated that the cut-off associated with a significant change in the image quality was 80 mm for posterior uterine wall depth (score difference, 1.06; P < 0.001) and 70 mm for crown-rump length (score difference, 0.77; P = 0.001). In the group of women with two values above these cut-off points, an average score decrease of 1.90 (P < 0.001) was observed. CONCLUSIONS: The quality of fetal nuchal translucency measurement is poorer when the fetal crown-rump length is > 70 mm and the posterior uterine wall depth is > 80 mm.

Crown-Rump Length↗

Reconstructed measurements produced from ultrasound images using a computerized system.

OBJECTIVE: The aim of this study was to evaluate the feasibility and accuracy of reconstructed measurements produced from video-printed ultrasound images. DESIGN: Reproduction of reconstructed measurements using designated software and comparison of the results with regular measurements derived from the same images. SUBJECTS: Seventy regular sonographic examinations of biparietal diameter (BPD) and nuchal translucency (NT) thickness. METHODS: The study included 35 conventional-size (BPD) and 35 small-size (NT) measurements. Each image was measured twice during a dynamic ultrasound examination (regular measurements) and twice using a computerized system (reconstructed measurements). The latter comprised three steps: (i) computerization (computer-generated images by scanning); (ii) calibration (using the scale located alongside the image); (iii) measurement (placing the calipers at the desired points). RESULTS: All images were successfully scanned, and the computer-generated images were of sufficient quality for proper measurement. There was no difference between mean values of regular and reconstructed BPD measurements, 63.9 mm (3.7 mm, SE) and 63.6 mm (3.8 mm, SE), respectively. Similarly, mean values of regular NT measurements were similar to the reconstructed ones, 1.48 mm (0.09 mm, SE) and 1.49 mm (0.09 mm, SE), respectively. Repeated regular BPD and NT measurements exhibited repeatability coefficients of 1.6 mm and 0.4 mm, respectively. These values were smaller than those obtained by repeated reconstructed measurements of 2.1 mm and 0.52 mm, respectively. CONCLUSIONS: Reconstructed measurements of ultrasound video-printed images are feasible, require modest facilities and exhibit more than reasonable accuracy. This option may contribute to medical research, audit, quality control and training, as well as to medico-legal issues.

Feasibility Studies↗

Transvaginal sonographic assessment of cervical length changes during triplet gestation.

The current study aimed to evaluate the contribution of transvaginal sonography (TVS) for monitoring cervical changes during the second half of triplet gestation. Forty-five pregnant women with triplets pregnancies were prospectively scanned by TVS from approximately 26 weeks gestation and were longitudinally followed-up until delivery. Based on a receiver-operating curve it was found that a cervical length of 25 mm is the most accurate parameter (94% sensitivity and 45% specificity) for predicting premature delivery < or =33 gestational weeks. Thus, a single cervical length measurement of < or =25 mm at 26 weeks gestation correlated well with premature delivery at < or =33 weeks (chi(2); P = 0.002). Using the linear regression model, a mathematical equation [(Week of delivery = 27.4 + 1.6 x cervical length; R(2) = 0.46; P = 0.01)] for predicting the gestational age of delivery (dependent variable) was determined based on mid-gestation cervical measurements (predictors). In parturient women with triplet gestation, TVS assessment of the uterine cervix offers insight into the cervical status and provides valuable information for prenatal care. This includes both monitoring the cervical changes throughout third trimester as well as predicting the likelihood of premature delivery.

Adult↗

Nuchal translucency measurement and pregnancy outcome after assisted conception versus spontaneously conceived twins.

BACKGROUND: Nuchal translucency (NT) measurement for Down's syndrome screening or detecting various fetal anomalies is a reliable sonographic marker. This study evaluates the contribution of NT screening in spontaneously conceived and assisted conception twin pregnancies. METHODS AND RESULTS: Maternal age at measurement, chorionicity, ultrasound features, karyotype results and pregnancy outcome were recorded prospectively and compared in 83 assisted reproduction treatment and 91 spontaneously conceived twins. Pregnancy outcome was evaluated according to maternal age, method of conception, NT data and chorionicity. NT measurements (> or =95 centiles of the normal range) were considered screen-positive and mid-pregnancy fetal karyotyping was advised. Complicated pregnancy outcome, which could be signalled by increased NT, was defined as either chromosomal abnormalities, severe structural defects or fetal demise. Based on NT measurements, 16 fetuses (4.6%) were found to be screen-positive. Five of them had chromosomal aneuploidy and selective termination was performed. The parents also opted for this procedure in another five fetuses because of major structural abnormality diagnosed during NT assessment. No other chromosomal or major fetal abnormality were found post-natally. Although no difference was found in NT, crown-rump length and maternal age between spontaneous and assisted reproduction technology twin pregnancies, the former group had a significantly higher rate of screen-positive results (7 versus 2%, P = 0.047), amniocentesis uptake (33 versus 22%, P = 0.014), monochorionic twining (32 versus 4%, P = 0.001) and complicated pregnancy outcome (11 versus 5%, P = 0.02). CONCLUSION: The present study confirms that first trimester target scanning can improve outcome by early detection and management of cases with an anomalous co-twin. It also identifies some differences between spontaneously and artificially conceived twin pregnancies in relation to this area of testing.

Abortion, Induced↗