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Biomedical subjects

A Herman

Publications and source records attributed to A Herman.

At least 55 records · Page 3Linked to original sources
PubMed2001

Mutations of ovine and bovine placental lactogens change, in different ways, the biological activity mediated through homologous and heterologous lactogenic receptors.

The biological activities of ovine (o) and bovine (b) placental lactogens (PLs) and their mutated analogues were compared using several binding and in vitro bioassays. In almost all cases, the biological activities of these analogues mediated through rat (r) prolactin receptor (PRLR) showed little or no change, despite a remarkable decrease in their capacity to bind to the extracellular domain of rPRLR and despite compromised stability of the 2:1 complexes. These results indicate that mutations impairing the ability of oPL or bPL to form stable complexes with lactogenic receptors do not necessarily lead to a decrease in the biological activity, because the transient existence of the homodimeric complex is still sufficient to initiate the signal transduction. In contrast, oPL and bPL analogues completely, or almost completely, lost their ability to activate homologous PRLRs, and some of them even acted as site-2 antagonists. To explain the difference between the activity transduced through homologous and that transduced through heterologous PRLRs, we propose the novel term 'minimal time of homodimer persistence'. This concept assumes that in order to initiate the signal transduction, the associated kinase JAK2 has to be transphosphorylated and this requires a 'minimal time' of homodimer existence. In the case of homologous interaction between ruminant PLs and homologous PRLRs, this 'minimal time' is met, though the interaction with homologous PRLRs has a shorter half-life than that with heterologous PRLRs. Therefore oPL or bPL are active in cells possessing both homologous and heterologous PRLRs. Mutations of oPL or bPL lead to reduced affinity and, consequently, the 'time of homodimer persistence' is shortened. Although in the case of heterologous interaction the 'minimal time' is still sufficient to initiate the biological activity, in homologous interactions, which are already weaker than heterologous interactions, further destabilization of the complex shortens its persistence to below the 'minimal time', leading to full or partial loss of biological activity.

Animals↗
PubMed2001

[Prenatal Down's syndrome screening at 10-14 weeks gestation using the combined nuchal translucency and maternal serum biochemistry: preliminary results of the first 358 cases].

We report our preliminary experience of prenatal screening for Down's syndrome (DS) using nuchal translucency (NT) measurement combined with the serum biochemistry analysis of Free beta-human chorionic gonadotropin (F beta hCG) and pregnancy associated plasma protein A (PAPP-A) all measurement at 10-14 weeks of gestation. Of the 358 parturient women which enrolled in the study, 9 cases were not included because of fetal anomalies or miscarriages. Thus the study group included 349 singleton pregnancies in which complete prenatal and infant follow-up was available. Forty-four pregnant women were found to be screen positive (12.6%) and in 13 cases (27%) of them fetal chromosomal aneuploidies were diagnosed. Looking into the markers profile we found that the NT was a sensitive marker which was abnormally increased in all the fetal aneuploidies. Serum F beta hCG was found to be a promising marker as well, being significantly elevated (2.26 +/- 0.86 multiple of the medians, MoM) in DS cases, and decreased (< 0.5 MoM) in two cases of Edward's syndrome. On the contrary, PAPP-A was found less sensitive, and its mean MoM values were not significantly different between DS versus euploid fetuses. Our preliminary results support the promising success of DS screening using NT and F beta hCG.

Adult↗
PubMed2001

[Primary PTCA in the treatment of acute myocardial infarct. Experience at the Faculty Hospital in Hradec Kralove].

INTRODUCTION: Primary coronary angioplasty is at present a fully accepted and worldwide method of treatment of acute myocardial infarction. As proved by a number of randomized studies, this treatment is associated with a higher rate of coronary patency, a smaller infarction focus an better clinical results as compared with thrombolytic treatment. METHOD: The authors analyzed a register of 233 consecutively treated patients with primary coronary angioplasty in the Faculty Hospital in Hradec Králové with elevation of the ST sections on electrocardiographic examination during the period from September 1997-January 2001. RESULTS: Acute success defined as a residual stenosis < 30%, normal flow through the vessel (TIMI III) and survival for the first 24 hours was 91.0% and without patients with cardiogenic shock even 96.0%. The total mortality on hospitalization was 9.1%. The mortality of patients without cardiogenic shock was only 1.9%. A high mortality was recorded in patients in cardiogenic shock (74.0%). A stent was implanted in 65.0% patients, subacute thrombosis of the stent occurred in 1.9%. During a 6-month follow up the total mortality was 10.3%. The percentage of patients without any cardiovascular even (event free survival, EFS) after discharge from hospital was 81.0%. CONCLUSIONS: The authors provided evidence that primary coronary angiolpasty is a safe and highly effective method in the treatment of acute myocardial infarction. It is associated with a total hospitalization mortality of ca 10% and a mortality of less than 2% in patients without cardiogenic shock. Cardiogenic shock, on the other hand, remains a problem despite intensive treatment such as inotropic support, mechanical reperfusion and intraortal balloon counterpulsation. In the presented work the mortality of patients with cardiogenic shock was 74.1%. Implantation of a stent does not involve a major risk for the patient, the incidence of subacute thrombosis of the stent is low and does not differ from elective procedures. The fate of patients during the follow up after primary angioplasty is favourable. In the presented work the total 6-month mortality was 10.3% and EFS was 81.0%.

Angioplasty, Balloon, Coronary↗
PubMed2000

Functional heterodimerization of prolactin and growth hormone receptors by ovine placental lactogen.

Although homo- or heterodimerization are common mechanisms for activation of cytokine receptors, cross-talk between two distinct receptors in this superfamily has been never shown. Here we show a physiologically relevant example indicating that such an interaction does occurs, thus raising the hypothesis that heterodimerization between distinct cytokine receptors may be a novel mechanism contributing to the diversity of cytokine signaling. These findings were documented using both surface plasmon resonance and gel filtration experiments and show that ovine placental lactogen (PL) heterodimerizes the extracellular domains (ECDs) of ruminant growth hormone receptor (GHR) and prolactin receptor (PRLR). We also show that PL or PL analogues that exhibit little or no activity in cells transfected with PRLRs and no activity in cells transfected with ovine GHRs exhibit largely enhanced activity in cells cotransfected with both PRLRs and GHRs. Furthermore, chimeric receptors consisting of cytosolic and transmembrane part of ovine GHR or ovine PRLR and ECDs of human granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR) alpha or beta were constructed. Upon transfection into Chinese hamster ovary cells along with reporter luciferase gene and stimulation by GM-CSF, a significant increase in luciferase activity occurred when GM-CSFR-alpha-PRLR and GM-CSFR-beta-GHR or GM-CSFR-alpha-GHR and GM-CSRR-beta-PRLR were cotransfected. In conclusion, we show that ovine PL is capable of functional heterodimerization of GHR and PRLR and that when their cytosolic parts, coupled to the ECD of GM-CSF receptors, are heterodimerized by GM-CSF, they are capable of transducing biological signal.

Animals↗
PubMed2000

Combined first trimester nuchal translucency and second trimester biochemical screening tests among normal pregnancies.

We prospectively examined whether first trimester nuchal translucency (NT) and second trimester triple test (TT) results are correlated, and determined overlapping and mutual screen-positive rates. Results of NT, TT, amniocentesis and pregnancy outcome were obtained in 508 normal pregnancies. Inter-test correlation was performed by comparing the likelihood ratios (LR). Overlapping of screen-positive cases, of NT and TT, was determined by comparing mutual risks for Down syndrome (DS) livebirth of > or = 1:380. Combined screen-positive rates were evaluated by using summation risk (NT and/or TT exhibiting a risk > or = 1:380) and calculated risk (new risk > or / =1:380, based on multiplication of LR(NT) and LR(TT)). Screen-positive rates between NT and TT differed significantly and when either test showed an increased risk for DS, the probability of the other to predict the same was negligible (p<0.001). Overall screen-positive rates, at a risk > or = 1:380, were 2% and 5.7% for NT and TT, respectively. Summation and calculated combining methods were associated with 7.5% and 2.0% screen-positive rates, respectively. Amniocentesis was performed on 20.7% of the cases, mostly screen-negative ones. Our results showed that, in normal pregnancies, NT and TT do not correlate and that their combined calculated risk in normal pregnancies is associated with a low screen-positive rate of 2.0%.

Adult↗
PubMed2000

Conservative management of adnexal torsion in premenarchal girls.

STUDY OBJECTIVE: To evaluate treatment of premenarchal girls with torsion of the adnexa. DESIGN: Retrospective review of medical records (Canadian Task Force classification II-2). SETTING: Tertiary care, university-affiliated hospital. PATIENTS: Eight premenarchal girls (age range 3-12 yrs) with twisted adnexa. INTERVENTION: Laparoscopic detorsion and follow-up with B scan and Doppler ultrasound imaging. MEASUREMENTS AND MAIN RESULTS: Duration of complaints ranged from 8 to 72 hours (mean 34.6 hrs) and the interval from admission to surgery ranged from 6 to 24 hours (mean 18.7 hrs). Four patients had torsion of normal-appearing adnexa. The other four had ovarian neoplasms. Two had cystic mature teratomas (dermoid cysts) and one a serous cystadenoma that required additional operation. The fourth girl had a simple ovarian cyst that was aspirated laparoscopically. Seven girls (87%) had normal-appearing ovaries on follow-up ultrasound. In one patient, a small ovary was seen, with no intraovarian blood flow on color Doppler. CONCLUSION: Although the diagnosis of torsion of the adnexa in premenarchal girls is difficult and usually delayed, laparoscopic detorsion seems to be an effective adnexa-sparing approach. We suggest that laparoscopy should be the treatment of choice and that detorsion, rather than adnexectomy, be performed more often in these patients.

Adnexal Diseases↗
PubMed2000

On-to-on versus on-to-out nuchal translucency measurements.

OBJECTIVE: To analyze variables affecting the differences between on-to-on and on-to-out methods of nuchal translucency measurement. DESIGN: Prospective comparison of two methods of caliper placement. SUBJECTS: A total of 245 women undergoing transabdominal and 37 women undergoing transvaginal nuchal translucency scanning. METHODS: Nuchal translucency was measured using both on-to-on and on-to-out methods of caliper placement on the same frozen images. Differences between the methods were evaluated according to fetal size, nuchal thickness and mode of examination. Regression analysis was performed for the calculation of the expected difference between the methods at various combinations. Results among 1254 singleton pregnancies were used to set 50th, 95th and 97.5th centiles for the on-to-on method. The calculated differences were used to set 50th, 95th and 97.5th centiles for the on-to-out method. RESULTS: The mean difference between on-to-out and on-to-on nuchal translucency, using transabdominal scanning, was 0.95 +/- 0.14 mm. The differences were shown to correlate directly with fetal size and with nuchal thickness. In addition, scans performed transvaginally exhibited a smaller difference between the methods (0.90 mm vs. 0.94 mm; P < 0.05). CONCLUSION: The difference between on-to-on and on-to-out nuchal translucency measurements may have a considerable effect on the calculated risk for aneuploidy.

Abdomen↗
PubMed2000

Complicated third stage of labor: time to switch on the scanner.

This Editorial chronicles the current experience in ultrasound usage during pathologic events occurring in the third stage of labor. Further improvement in the technology for carrying out clinical research will improve our knowledge so that more information can be gleaned from this modality to bestow optimal management for such potentially dangerous conditions. Awareness of the capabilities of sonography may provide the motivation for its use, and obstetricians are encouraged to scan the third stage of normal deliveries for better recognition of normal findings and improved assessment of abnormal ones. Although final decisions should be based mainly upon sound clinical judgement, we contend that complicated third stage of labor warrants turning on the scanner.

Delivery, Obstetric↗
PubMed2000

Dominant partial epilepsies. A clinical, electrophysiological and genetic study of 19 European families.

Nineteen families with autosomal dominant partial epilepsy were analysed clinically and electrophysiologically in detail. Seventy-one patients were studied as well as 33 non-epileptic at-risk family members. We subdivided the families into those with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) (n = 8), familial temporal lobe epilepsy (n = 7) and autosomal dominant partial epilepsy with variable foci (n = 4). However, the application of this nosology to certain families was difficult in cases of non-specific or conflicting clinical and electrophysiological evidence. This was underscored by the observation by depth electrode recordings in one patient that a so-called ADNFLE may originate in an extrafrontal area. The evolution of familial partial epilepsies, which exhibit great intrafamilial variability, is not always benign. The level of pharmacoresistance may reach 30%, close to that seen in classical cryptogenic partial epilepsies. The familial character of a partial epilepsy may be unrecognized in small families as some affected members may have only EEG abnormalities and are clinically asymptomatic, which reflects incomplete clinical penetrance. In view of the recent discoveries of mutations in the alpha4 nicotinic acetylcholine receptor subunit in a few families with ADNFLE, this genetic study focused on genes encoding nicotinic receptor subunits and a candidate region on chromosome 10q. No mutation was detected in the alpha4 and 012 nicotinic acetylcholine receptor subunits. Positive but not significant lod scores were obtained in four families with markers from the candidate region on chromosome 10q.

Adolescent↗
PubMed2000

Pregnancy outcome and infant follow-up of fetuses with abnormally increased first trimester nuchal translucency.

The numbers of fetuses with an abnormal increased first trimester nuchal translucency (NT) but a confirmed normal anatomy and karyotyping is relatively small and therefore a challenge for prenatal counselling. The aim of the current study was to assess the long-term pregnancy outcome and infancy prognosis of 78 fetuses with NT > 95th centile of the normal range for crown-rump length (CRL). The most common abnormalities in this group were aneuploidy, which affected 32 of the fetuses followed by four and three cases which were miscarried or had cardiac defects respectively. The remaining euploid fetuses with normal detailed scans were followed throughout their infancy (mean 24 months; range 12-36 months). Post-natally, except for a correctable case of ventricular septal defect and a case of posterior urethral valve, no other abnormalities were detected. After excluding all aneuploid cases and using the maternal age as a second variable, an uncomplicated pregnancy outcome could be anticipated in 17 cases (100%) when the maternal age was <30 years and NT between 95th centile and 5 mm. However, the chance of a normal outcome dropped to 50% in four cases with maternal age > or =30 years and NT > or =5 mm (Fisher's exact test; P: = 0.02). These findings suggest that the long-term prognosis of the euploid fetuses with large NT (<5 mm) is reassuring in younger women.

Abortion, Spontaneous↗
PubMed2000

Death and injury from motor vehicle crashes in Colombia.

We report data on the distribution and determinants of road deaths and injuries for all victims in Colombia, with the aim of defining targets and priorities for highway death prevention in that country and other rapidly urbanizing nations. Using information from Colombia's Fund for the Prevention of Road Injury and the national death registry, we studied data on deaths and injuries from 1991 to 1995 for the nation as a whole and for the country's two largest cities, Santa Fe de Bogotá and Medellín. Deaths and injuries are rising in the nation as a whole. Of the deaths, 75% occur in urban areas, and 80% are in males. Pedestrians aged 15-34 are a peak subgroup. Thirty-four percent of deaths are attributable to speeding and/or alcohol consumption. Death tolls are highest at night and on weekends. Specific priority targets for intervention are indicated by the fact that 75% of road deaths in Colombia occur in urban areas and that 80% of all victims are males.

Accidents, Traffic↗
PubMed2000

Serum inhibin A levels in pregnant women with systemic lupus erythematosus or antiphospholipid syndrome.

Maternal serum inhibin A levels are increased on average in pregnancies affected by Down syndrome (DS). However, some reports have found increased serum levels in women with pre-eclamptic toxaemia as well. In the current study, maternal serum inhibin A was retrospectively measured in a series of 32 serum samples from pregnant women previously diagnosed as having either systemic lupus erythematosus (SLE) or primary antiphospholipid syndrome (APS). For comparison, normal medians were calculated from 57 unaffected control pregnancies together with a total of 854 samples tested at 13-19 weeks of gestation as part of the routine antenatal DS screening. All results were expressed in multiples of the gestation specific normal medians (MoM). A cubic regression formula was fitted, weighting for the number of women tested at each gestation. The median MoM value in the 16 cases of SLE and the 16 cases of primary APS is 0.60 (95% confidence interval 0.40-0.91) and 0.88 (95% confidence interval 0.66-1.17), respectively. For primary APS this was not statistically significant, whereas the SLE patients had a highly statistically significant reduction of serum inhibin A (p<0.002, Wilcoxon Rank sum Test, 2 tailed). Six pregnancies in the SLE group had a complicated obstetric outcome, i.e. missed abortion, placental abruption, exacerbation of the underlying disease which necessitated delivery, and severe postpartum haemorrhage. In 85% of this subgroup, serum inhibin A levels were below the normal 10th centile. The current data suggest that serum inhibin A is decreased on average in SLE patients. Those preliminary results might have various obstetric implications such as antenatal DS screening of SLE patients, identification of pregnant women at risk of developing SLE, who have presented for routine DS screening and for monitoring SLE patients throughout their pregnancy.

Antiphospholipid Syndrome↗
PubMed2000

Public-private partnerships in health care for developing countries: a new paradigm for change.

The shift in traditional corporate philanthropy policy and practices from one of objective giving to strategic investing is discussed along with the positive impact of these changes as realized through a social awareness and the emerging new paradigm of public private partnerships. Examples of corporate support with focus on a case study concerning HIV/AIDS in Africa are presented within the context of lessons learned. These examples illustrate how public and private sectors working together, can maximize the potential philanthropic endeavor. Using strategically directed, yet humanitarian and culturally sensitive efforts, managed care organizations may find the concepts and negotiations inherent to philanthropic partnerships a familiar setting, and would therefore be suitable candidates to engage in public-private partnerships.

Africa South of the Sahara↗
PubMed2000

[Percutaneous rescue transluminal coronary angioplasty].

Rescue angioplasty is an operation performed in the acute stage of myocardial infarction where systemic thrombolysis did not lead to opening of the artery. Investigations made in recent years indicate the benefit of rescue angioplasty only in those patients where the infarcted artery is patent several hours after evidence that thrombolysis failed. At the same time they provide evidence of the increasing safety and technical success of the operation. The authors present a brief review of the literature pertaining to the development of views, and emphasize the need of early and correct indication.

Angioplasty, Balloon, Coronary↗
PubMed1999

[Screening for Down's syndrome at week 10-14 by measuring fetal nuchal translucency thickness].

Increased fetal muchal translucency (NT) thickness at 10-14 weeks of gestation may indicate underlying fetal chromosomal abnormalities, anatomical anomalies and genetic syndromes. Between January 1997 and May 1998, 1400 women 10-14 weeks pregnant underwent sonographic screening for detection of Down's syndrome (DS). Follow-up was complete in 1208 (86%). Maternal age ranged from 17-44 years (mean 18.0). 87% were found by screening to have a higher risk (1:380) for DS diagnosed at birth. All these fetuses were karyotyped and 8 had chromosomal abnormalities. 2 fetuses with normal NT were diagnosed later as having DS, 1 by the mid-gestation triple test and 1 by amniocentesis because of advanced maternal age. Thus sonographic screening identified 8 out of 10 fetuses found to have chromosomal abnormalities at birth. Neonates not karyotyped before birth had no traits at birth that justified chromosomal analysis. Results of this study suggest that NT measurement, combined with maternal age, is an effective 1st trimester screening method for DS in an unselected obstetric population.

Adolescent↗
PubMed1999

Clinical and MRI findings in spinocerebellar ataxia type 5.

Spinocerebellar ataxia type 5 (SCA5), one of the genetically heterogeneous autosomal dominant cerebellar ataxias, was assigned to chromosome 11 in a single family descending from the grandparents of President Abraham Lincoln. We report a second, apparently unrelated, SCA5 family of French origin. The overall clinical picture was a slowly progressive cerebellar syndrome beginning mostly in the third decade (27+/-10 years, range 14 to 40). MRI showed a marked global cerebellar atrophy similar to SCA6.

Female↗
PubMed1999

[Pregnancy outcome in fetuses with increased nuchal translucency thickness at 10-14 weeks of pregnancy].

Increased thickness of fetal nuchal translucency (TNT) measured at 10-14 weeks of gestation, may suggest underlying fetal chromosomal defects, structural abnormalities or genetic syndromes. We examined the relationship between increased TNT and pregnancy outcome, especially in fetuses with normal karyotypes. 1400 pregnant women underwent first trimester scanning and screening for chromosomal abnormalities and measurement of fetal TNT. 25 fetuses (2%) with increased TNT (> 3 mm) were identified. 8 (30%) had an abnormal karyotype. Of these, 5 pregnancies were aborted, 3 ended in spontaneous abortions before karyotyping, and 2 were terminated, all before detailed cardiac scanning. There was a high association between increased TNT and karyotype abnormalities. The total incidence of favorable outcome in fetuses with normal chromosomal and cardiac features but enlarged TNT was 56%.

Abortion, Induced↗