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F Picard

Publications and source records attributed to F Picard.

At least 37 records · Page 2Linked to original sources
PubMed2000

Genome search for susceptibility loci of common idiopathic generalised epilepsies.

Genetic factors play a major role in the aetiology of idiopathic generalised epilepsies (IGEs). The present genome scan was designed to identify susceptibility loci that predispose to a spectrum of common IGE syndromes. Our collaborative study included 130 IGE-multiplex families ascertained through a proband with either an idiopathic absence epilepsy or juvenile myoclonic epilepsy, and one or more siblings affected by an IGE trait. In total, 413 microsatellite polymorphisms were genotyped in 617 family members. Non-parametric multipoint linkage analysis, using the GeneHunter program, provided significant evidence for a novel IGE susceptibility locus on chromosome 3q26 (Z(NPL) = 4.19 at D3S3725; P = 0.000017) and suggestive evidence for two IGE loci on chromosome 14q23 (Z(NPL) = 3.28 at D14S63; P = 0.000566), and chromosome 2q36 (Z(NPL) = 2.98 at D2S1371; P = 0.000535). The present linkage findings provide suggestive evidence that at least three genetic factors confer susceptibility to generalised seizures in a broad spectrum of IGE syndromes. The chromosomal segments identified harbour several genes involved in the regulation of neuronal ion influx which are plausible candidates for mutation screening.

Chromosomes, Human, Pair 14↗
PubMed2000

A novel missense mutation (C30S) in the gene encoding tumor necrosis factor receptor 1 linked to autosomal-dominant recurrent fever with localized myositis in a French family.

OBJECTIVE: To characterize both phenotypic (clinical features and magnetic resonance imaging [MRI] findings) and genotypic aspects of autosomal-dominant recurrent fever, also known as tumor necrosis factor receptor (TNFR)-associated periodic syndrome (TRAPS), in a French family and to investigate the role of the mutated 55-kd tumor necrosis factor alpha (TNFalpha) receptor (TNFR1) in the pathogenesis of the disease. METHODS: The coding region of TNFR1 was sequenced in 2 individuals with TRAPS (the propositus and her grandfather) and in 3 clinically unaffected relatives. Expression of soluble TNFR1 (sTNFR1) was investigated in 3 of the family members carrying a C30S mutation in TNFR1, and was compared with the levels of soluble TNFR2 (sTNFR2) by enzyme-linked immunosorbent assay. The membrane TNFR1 expression was then compared with membrane TNFR2 levels at the surface of peripheral blood mononuclear cells by flow cytometric analysis. The clinical heterogeneity in this French family was investigated by searching polymorphic variants in the TNFalpha promoter by DNA sequencing. RESULTS: Both the disease course and the clinical presentation in the propositus were highly indicative of TRAPS. MRI study of the segmental inflammatory process in the limbs showed abnormal signals in the muscle and subcutaneous tissue without involvement of adjacent joints or fascia. A novel missense mutation, C30S, in the first extracellular N-terminal cysteine-rich domain (CRD1) of TNFR1 was characterized in the propositus, her affected grandfather, and her clinically unaffected father. Expression of membrane TNFR1 at the surface of monocytes and polymorphonuclear leukocytes, as well as the levels of sTNFR1 in serum when the disease was not active were not modified in the 3 individuals carrying the TNFR1 C30S mutation. In contrast, during attacks, sTNFR1 levels remained abnormally low, as compared with the levels in unrelated patients with active adult-onset systemic Still's disease. The clinical heterogeneity could not be explained by a polymorphic variant in the TNFalpha promoter. CONCLUSION: TRAPS is a distinct clinical and radiologic disease entity that is responsible for recurrent fever and migratory cellulitis-like processes with localized myositis. We have identified a novel TNFR1 mutation, C30S, that is located in the CRD1 domain in a French family affected by the disease. This mutation seems to affect the level of sTNFR1, which did not increase in the propositus during inflammatory attacks.

Adolescent↗
PubMed2000

Abnormal insulin and beta-adrenergic modulation of lipoprotein liipase during refeeding after prolonged fasting in the Zucker rat.

AIMS/HYPOTHESIS: To characterise the response of tissue lipoprotein lipase to refeeding after prolonged (24 h) fasting in lean and obese Zucker rats, and to verify whether lipoprotein lipase in obese rats is resistant to the short-term action of insulin and escapes modulation by the beta-adrenergic pathway. METHODS: Lean Fa/? and obese fa/fa male Zucker rats fasted for 24 h and refed at will. Lipoprotein lipase activity in adipose and muscle tissues was assessed in the freely fed and fasted states and at various times during refeeding, with or without beta-adrenergic blockade (propranolol). RESULTS: The 24 h fast erased the phenotype-related differences in insulinaemia and adipose lipoprotein lipase activity present in freely fed rats. Adipose lipoprotein lipase increased twofold in obese rats 1 h after refeeding, whereas no change occurred at that time in lean rats. Activity remained at that level for at least 6 h after refeeding in obese rats, whereas in lean animals it was increased fivefold after 6 h of refeeding. In muscle of obese rats, lipoprotein lipase decreased in response to refeeding, but paradoxically increased twofold in lean animals. Giving propranolol to lean rats before refeeding abolished the atypical response of muscle lipoprotein lipase to food intake and restored the early (1 h after refeeding) increase in adipose lipoprotein lipase but had no effect in obese rats. CONCLUSION/INTERPRETATION: Refeeding after prolonged fasting activates the P-adrenergic pathway in lean rats, which transiently counteracts insulin-mediated modulation of lipoprotein lipase. The P-adrenergic pathway is not activated by refeeding in adipose tissue and muscle of the obese Zucker rat. In the obese Zucker rat, the early modulation of adipose lipoprotein lipase activity is abnormal upon refeeding after prolonged fasting, suggesting short-term resistance to the action of insulin.

Adipose Tissue↗
PubMed2000

Activity of the caspase-3/CPP32 enzyme is increased in "early stage" myelodysplastic syndromes with excessive apoptosis, but caspase inhibition does not enhance colony formation in vitro.

OBJECTIVE: Excessive apoptosis may have a role in the ineffective hematopoiesis and cytopenias observed in myelodysplastic syndromes. The goals of this study were 1) to quantify apoptosis in patients with "early stage" myelodysplasia [including patients with refractory anemia (RA), RA with ringed sideroblasts (RARS), RA with excess blasts and with less than 10% blasts (RAEB(<10))], and in patients with "late stage" myelodysplasia [including RAEB with more than 10% blasts (RAEB(>10)), RAEB in transformation (RAEB-t), and acute myeloid leukemia secondary to myelodysplasia (LAM2)]; 2) to study the activation of the caspase-3/CPP32 enzyme, a major "effector" caspase in hematopoiesis, in patients with "early stage" myelodysplasia, and 3) to evaluate the effect of caspase inhibition on the apoptotic phenotype and clonogenicity of hematopoietic progenitors in vitro in these patients. MATERIALS AND METHODS PATIENTS: Fifty-four patients with myelodysplastic syndromes, including 30 with "early stage" myelodysplasia and 24 with "late stage" myelodysplasia were studied. Study of apoptosis: TUNEL assay performed on bone marrow smears and/or quantification of annexin V positive bone marrow mononuclear cells by flow cytometric analysis. Caspacse-3/CPP32 activity: Quantitative measurement of caspase-3/CPP32 activity on total bone marrow mononuclear cells using a fluorogenic substrate. Effect of the caspase-inhibitor Z-VAD-FMK: 1) on the apoptotic phenotype of total bone marrow mononuclear cells and 2) on the clonogenicity of hematopoietic progenitor cells. RESULTS: The group of 30 patients with "early stage" myelodysplasia had statistically increased apoptosis compared to the group of 24 patients with "late stage" myelodysplasia (44.1% +/- 4.8 vs 21.8% +/- 3.6; p = 0.02) using the TDT-mediated dUTP nick-end labeling (TUNEL) assay. In the group of patients with RAEB, those with MDS(RAEB<10) had excessive apoptosis compared to those with MDS(RAEB>10) (44.0% +/- 3.5% vs 29.5% +/- 3.6%;p = 0.042) The median caspase-3 activity in 20 "early stage" myelodysplasia patients was 19,000 U (range 3,460-41,000) and significantly increased compared to normal individuals (4,256 U, range 3,200-5,200; p = 0.032) Bone marrow mononuclear cells from 12 "early stage" MDS patients (including 11 from the 20 studied for caspase-3 activity) were incubated with or without the broad-spectrum caspase inhibitor Z-VAD-FMK. In 4 of 9 evaluable patients (44.4%) with excessive apoptosis, the number of annexin V positive cells decreased in a dose-dependent manner in the presence of Z-VAD-FMK. However, in none of these patients was caspase inhibition with Z-VAD-FMK able to enhance colony formation in vitro. CONCLUSION: These results confirm that a major characteristic of patients with "early stage" myelodysplasia is increased apoptosis. The results also indicate that excessive apoptosis in these patients is accompanied by increased caspase-3/CPP32 activity. However, caspase inhibition with the broad-spectrum inhibitor Z-VAD-FMK cannot improve hematopoiesis in this group of patients, even when apoptosis is attenuated.

Amino Acid Chloromethyl Ketones↗
PubMed2000

Synthesis of N-substituted piperidine-4-(benzylidene-4-carboxylic acids) and evaluation as inhibitors of steroid-5alpha-reductase type 1 and 2.

The synthesis of N-substituted piperidine-4-(benzylidene-4-carboxylic acids) is described [benzoyl (1), benzyl (2), adamantanoyl (3), cyclohexanoyl (4), cyclohexylacetyl (5), diphenylacetyl (6), dicyclohexylacetyl (7), 2-propylpentanoyl (8), diphenylcarbamoyl (9), trimethylacetyl (10), 3,3-dimethylacryloyl (11), dicyclohexylacetyl derivative of the benzyl compound (12)]. Compounds were tested for inhibitory activity toward 5alpha-reductase isozymes 1 and 2 in human and rat. The test compounds inhibited 5alpha-reductase, showing a broad range of inhibitory potencies. In rat, compounds 6 (IC50 = 3.44 and 0.37 microM for type 1 and 2, respectively) and 9 (IC50=0.54 and 0.69 microM for type 1 and 2, respectively) displayed the best inhibition toward both isozymes. Compound 7 showed a strong inhibition toward type 2 human and rat enzyme (IC50 = 60 and 80 nM) but only a moderate activity versus type 1 enzyme (IC50 approximately 10 microM for rat and human enzyme). In vivo, selected compounds reduced prostate weights in castrated testosterone treated rats.

5-alpha Reductase Inhibitors↗
PubMed2000

Severe but reversible encephalopathy associated with cefepime.

In this study, a report has been made of 19 cases of severe encephalopathy in patients with renal impairment who were treated during the last three years for various infections with cefepime, a new parenteral cephalosporin antibiotic. All patients (aged 57 to 91 years) presented a prolonged confusional state associated with diffuse rhythmic non-reactive triphasic sharp waves on the EEG. All the electroclinical symptomatology disappeared within 24-48 hours after discontinuation of drug administration. A clear relation was found between encephalopathy and cefepime intake. These observations underline the fact that the cefepime dosage should be reduced in renally impaired patients.

Aged↗
PubMed2000

Topiramate reduces energy and fat gains in lean (Fa/?) and obese (fa/fa) Zucker rats.

OBJECTIVE: This study examined the effects of topiramate (TPM), a novel neurotherapeutic agent reported to reduce body weight in humans, on the components of energy balance in female Zucker rats. RESEARCH METHODS AND PROCEDURES: A 2 x 3 factorial experiment was performed in which two cohorts of Zucker rats differing in their phenotype (phenotype: lean, Fa/?; obese, fa/fa) were each divided into three groups defined by the dose of TPM administered (dose: TPM 0, vehicle; TPM 15, 15 mg/kg; TPM 60, 60 mg/kg). RESULTS: The reduction in body weight gain induced by TPM in both lean and obese rats reflected a decrease in total body energy gain, which was more evident in obese than in lean rats. Whereas TPM administration did not influence the intake of digestible energy in lean rats, it induced a reduction in food intake in obese animals. In lean, but not in obese rats, apparent energy expenditure (as calculated by the difference between energy intake and energy gain) was higher in rats treated with TPM than in animals administered the vehicle. The low dose of TPM decreased fat gain (with emphasis on subcutaneous fat) without affecting protein gain, whereas the high dose of the drug induced a reduction in both fat and protein gains. The effects of TPM on muscle and fat depot weights were representative of the global effects of TPM on whole body fat and protein gains. The calculated energetic efficiency (energy gain/energy intake) was decreased in both lean and obese rats after TPM treatment. TPM dose independently reduced hyperinsulinemia of obese rats, but it did not alter insulinemia of lean animals. DISCUSSION: The present results provide sound evidence for the ability of TPM to reduce fat and energy gains through reducing energetic efficiency in both lean and obese Zucker rats.

Adipose Tissue↗
PubMed2000

Effects of the estrogen antagonist EM-652.HCl on energy balance and lipid metabolism in ovariectomized rats.

OBJECTIVE: The estrogen antagonist EM-652.HCl behaves as a highly potent and pure antiestrogen in human breast and uterine cancer cells. Because of its pure antiestrogenic activity in these cells, and because its prodrug, EM-800, reduces bone loss and decreases serum cholesterol and triglycerides in the rat, EM-652.HCl can be classified as a pure selective estrogen receptor modulator (SERM). This study was conducted to assess the ability of EM-652.HCl to prevent obesity and abnormalities of lipid metabolism induced by ovariectomy in a rat model. DESIGN: Female rats were left intact or ovariectomized (OVX), and OVX rats were treated with placebo, estradiol (E2), or EM-652.HCl for 20 days. At the end of the treatment period, parameters of energy balance and determinants of lipid metabolism were assessed. RESULTS: As expected, OVX increased energy intake, which in turn was accompanied by an increased energy, fat and protein gain and higher food efficiency. OVX also increased the triglyceride content of the liver and produced hypercholesterolemia and hyperinsulinemia. The weight of representative white adipose depots was higher in OVX than in intact rats. Lipoprotein lipase activity was higher in white adipose tissues of OVX rats than in those of intact animals, whereas its activity was lower in oxidative tissues (brown adipose and soleus muscle). Replacement therapy with a physiological dose of E2 prevented most of the abnormalities in energy and lipid metabolism brought about by OVX, although its orexigenic effect was only partially corrected. In contrast, treatment of OVX rats with EM-652. HCl completely abolished OVX-induced obesity and its related abnormalities in lipid metabolism and glucose/insulin homeostasis. CONCLUSION: These findings demonstrate that EM-652.HCl can be considered as an effective agent to prevent OVX-induced obesity. The present study also shows that EM-652.HCl reduces cardiovascular risk factors associated with obesity such as hyperlipidemia and insulin resistance.

Animals↗
PubMed2000

Nitric oxide: a new player in the modulation of energy metabolism.

Nitric oxide (NO) is a key messenger molecule in several cell types. NO formation is catalyzed by a family of NO synthases (NOS) that use L-arginine as a substrate. Rat adipose tissue expresses the inducible, macrophage-type, nitric oxide (NO) synthase isoform (iNOS). Systemic administration of the bacterial endotoxin lipopolysaccharide (LPS) markedly increases the expression and activity of iNOS in both white and brown adipose tissues, as well as in skeletal muscle. iNOS induction can be reproduced in vitro by treatment of cultured white or brown adipocytes or L6 myocytes with LPS and inflammatory cytokines (TNFalpha, IFNgamma). The physiological role of NO in adipose tissues and skeletal muscle is still obscure. Recent evidence suggests that NO may be implicated in the regulation of energy metabolism. Using both pharmacological and genetic models of iNOS invalidation, we have recently begun to uncover a role for NO in the modulation of glucose transport and lipoprotein hydrolysis. These studies support the emerging concept that NO may fulfill the dual role of modulating energy metabolism in both physiological and pathological conditions as well as contributing to local immune defense during inflammatory processes.

Adipose Tissue↗
PubMed2000

Jumping translocation in acute leukemia of myelomonocytic lineage: a case report and review of the literature.

Jumping translocation (JT) is a very rare cytogenetic event, occurring especially in cancer. We describe a case of secondary acute monocytic leukemia (AML5b) with a JT involving the 3q13-3qter segment and leading to a partial trisomy 3. Each clone with JT was associated with trisomy 8 or tetrasomy 8. The literature of JT in AML cases is reviewed: only 13 cases of AML associated with JT have been previously described, seven of which are AML4/5 FAB subtype. Jumping translocation involvement in leukemogenesis is discussed. Leukemia (2000) 14, 119-122.

Adult↗
PubMed2000

Therapy-related acute myeloid leukaemia after successful therapy for acute promyelocytic leukaemia with t(15;17): a report of two cases and a review of the literature.

We describe two patients with positive t(15;17) acute promyelocytic leukaemia (APL) that developed into a therapy-related myelodysplasia 2-2.5 years after complete remission (CR) and then evolved into therapy-related acute myeloid leukaemia (t-AML). Both patients received anthracyclines as potential leukaemogenic drugs. In both cases, cytogenetic changes usually occurring after use of alkylating agents were noticed: monosomy 7 associated with monosomy 5 or 5q- chromosome. A review of the literature on t-AML occurring after successful therapy for APL showed only one report similar to these two cases. These observations suggest that anthracyclines can cause t-AML similar to that induced by alkylating agents.

Adult↗
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

[Inflammation of the myocardium as an arrhythmia trigger].

In patients with acute or chronic myocarditis, arrhythmias are a common and often the only clinical symptom in the natural course of the disease. The potentially malignant tachy- and bradyarrhythmias are of particular significance in the differential diagnosis of sudden cardiac death in myocarditis. Factors responsible for the increased incidence of cardiac arrhythmias are structural changes, parameters of ventricular dynamics and vascular changes. On the one hand, inflammatory processes in the cardiac myocytes and interstitium can lead directly to fluctuations in membrane potential. Fibrosis and scarring of the myocardial tissue and secondary hypertrophy and atrophy of the myocytes favor the development of ectopic pacemakers, late potentials and reentry as a result of inhomogeneous stimulus conduction. Furthermore, parameters of ventricular dynamics such as increased wall tension, increased myocardial oxygen consumption and diminished coronary reserve in the case of disturbed systolic or diastolic left ventricular function also contribute to the increased incidence of arrhythmias. Lastly, vascular factors can further increase the arrhythmogenicity of the inflamed myocardium through the disturbance of micro- and macrovascular perfusion and the resulting myocardial ischemia. Non-invasive rhythmological evaluation by 24 h Holter ECG, measurement of ventricular late potentials and heart rate variability can be used for orienting risk stratification of the at-risk patient with myocarditis. Programmed atrial and ventricular electrophysiological stimulation also has a relatively high predictive value for spontaneous ventricular tachyarrhythmias. It should be emphasized that, at the present time, optimal electrophysiological parameters with a high predictive value do not exist. In a selected patient population, immunosuppressive therapy in addition to conventional antiarrhythmic therapy can lead to the reduction or complete suppression of spontaneous and inducible arrhythmias. Nevertheless, in the interim, further precautionary antiarrhythmic measures such as serial antiarrhythmic treatment, VT ablation and ACID implantation are necessary in patients with malignant cardiac arrhythmias. Right ventricular myocardial biopsy for demonstration or exclusion of myocarditis is an important additional examination which can improve the differential diagnosis and treatment of patients with cardiac arrhythmias of unclear etiology.

Adult↗
PubMed2000

Encephalopathy with epileptic spasms resolved with corticoids in a 69 year-old patient.

A 69 year-old man with a history of recent temporal lobe seizures, presented with progressive coma and frequent epileptic spasms. Ictal EEG, PET and SPECT alterations were strikingly similar to those described in infantile spasms. Conventional antiepileptic drugs were ineffective but the introduction of corticoids induced a dramatic improvement with disappearance of the spasms. The etiology remains unknown. Epileptic spasms may occur in the elderly. If conventional antiepileptic drugs are ineffective, corticoids should be tried immediately.

Aged↗
PubMed1999

Megakaryocyte growth and development factor-induced proliferation and differentiation are regulated by the mitogen-activated protein kinase pathway in primitive cord blood hematopoietic progenitors.

In several erythroleukemia cell lines, activation of mitogen-activated protein kinases (MAPK) by phorbol esters or megakaryocyte growth and development factor (MGDF) is required for induction of megakaryocytic phenotype and growth arrest. To support this model, we have examined the effect of a specific inhibitor of this pathway (PD98059) on human CD34(+) hematopoietic progenitors isolated from cord blood (CB), induced to differentiate along the megakaryocytic lineage in liquid cultures supplemented with rhuMGDF. RhuMGDF induced a sustained activation of MAPK in megakaryocytes and this activation was completely inhibited in the presence of low concentrations of PD98059 (6 to 10 micromol/L). At this concentration, PD98059 induced an increase in cell proliferation, resulting in accumulation of viable cells and a prolongation of the life time of the cultures. This increase correlated with an increase in DNA synthesis rather than with a reduction in apoptosis. This effect was combined with developmental changes indicative of delayed megakaryocytic differentiation: (1) PD98059-treated cells tended to retain markers of immature progenitors as shown by the increased proportion of both CD34(+) and CD41(+)CD34(+) cells. (2) PD98059-treated cultures were greatly enriched in immature blasts cells. (3) PD98059 increased megakaryocytic progenitors able to form colonies in semisolid assays. Thus, the MAPK pathway, although not required for megakaryocyte formation, seems to be involved in the transition from proliferation to maturation in megakaryocytes. Inhibition of MAPK activation also led to an increase in the number and size of erythroid colonies without affecting granulocyte/macrophage progenitor numbers suggesting that, in addition to the megakaryocytic lineage, the MAPK pathway could play a role in erythroid lineage differentiation.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1999

Intensified-dose (4 gm/m2) cyclophosphamide and granulocyte colony-stimulating factor administration for hematopoietic stem cell mobilization in refractory rheumatoid arthritis.

OBJECTIVE: To evaluate the feasibility, safety, and efficacy of intensified-dose cyclophosphamide (ID-CYC), followed by granulocyte colony-stimulating factor (G-CSF) administration for collection of peripheral blood hematopoietic stem cells (HSC), for patients with severe, refractory rheumatoid arthritis (RA). METHODS: Four patients with severe refractory RA were enrolled in this open study. They received a single infusion of CYC (4 gm/m2) at day 0 followed by G-CSF (5 microg/kg/day) from day 6 until the last day of leukapheresis (performed at the time of hematopoietic recovery) to harvest peripheral blood HSC. Patients were monitored for disease activity, adverse effects, and hematopoietic reconstitution following this procedure. RESULTS: For all patients, administration of ID-CYC induced an early, dramatic improvement of disease activity. Long-term followup indicates that partial disease relapse was observed for all patients. No adverse effect was directly attributable to the treatment procedure. For most patients, HSC collection was sufficient to provide a graft enriched in CD34+ cells by positive selection as well as an unselected rescue graft. CONCLUSION: Patients with severe, refractory RA can benefit from ID-CYC. This procedure, followed by G-CSF administration, appears safe and technically suitable. In addition, it allows immediate improvement of RA activity that can occasionally persist beyond 6 months.

Adult↗
PubMed1999

Reliability and clinical application of fetal RhD genotyping with two different fluorescent duplex polymerase chain reaction assays: three years' experience.

OBJECTIVE: This study was designed to evaluate accuracy and clinical usefulness of fetal RhD genotyping with fluorescent duplex polymerase chain reaction. STUDY DESIGN: Two RhD-specific gene fragments (exon 10 in polymerase chain reaction 1 and exon 7 in polymerase chain reaction 2) were amplified in samples from 213 fetuses. RESULTS: Amplification failed in 0.9% of the specimens, and equivocal results were found in 1.4% of the specimens. Of the analyses, 6.6% had to be repeated. The concordance of genotyping and serotyping was 99.0% for each polymerase chain reaction. False-positive results were noted in 4 fetuses. Concordant findings from both assays indicated the correct serotype for all fetuses. In 44 alloimmunized pregnancies, further invasive procedures were avoided for 5 of the 6 genotypically RhD-negative fetuses. Only two of 38 RhD-positive fetuses had a hemoglobin level <8 g/dL at first fetal blood sampling. CONCLUSIONS: Fetal genotyping at distinct regions of the RhD gene is reliable and improves the care management of sensitized women.

Amniotic Fluid↗