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Biomedical subjects

P Hohlfeld

Publications and source records attributed to P Hohlfeld.

89 records · Page 5Linked to original sources
PubMed1993

Diagnosis and management of foetal thrombocytopenia.

Platelet counts remain stable during intrauterine life (245 +/- 65 x 10(9)/litre, mean +/- SD). Before diagnosing thrombocytopenia (< 150 x 10(9)/litre), a foetal blood sample must be checked for contamination with amniotic fluid, since even slight contamination can activate coagulation and lead to a false positive result. In this paper, we review the major causes of thrombocytopenia and discuss their pathogenesis and management. Foetal thrombocytopenia can be caused by maternal complications (immune thrombocytopenic purpura, neonatal alloimmune thrombocytopenia, gestational thrombocytopenia, preeclampsia, alloimmune haemolytic disease) or infectious diseases (toxoplasmosis, cytomegalovirus, rubella) or be of true foetal origin (chromosomal abnormalities, malformations, congenital thrombocytopenia, intrauterine growth retardation.

Female↗
PubMed1993

Plasma/serum protein patterns in human fetuses and infants: a study by high-resolution two-dimensional polyacrylamide gel electrophoresis.

Plasma/serum proteins of fetal blood samples (N = 88) obtained under ultrasound guidance between the 18th and the 39th week of pregnancy, of blood samples collected from premature infants (N = 19), newborns at term (N = 20) and children of less than 5 years of age (N = 55) were analysed by high-resolution two-dimensional polyacrylamide gel electrophoresis. By comparison with adult 'reference' protein maps, tens of different proteins (and some of their genetic variants) were identified on the electrophoretograms. After the 18th week of gestation, albumin, transferrin, Factor B, glu- and lys-plasminogen, antithrombin III, Gc-globulin, alpha 1-antitrypsin, alpha 2-HS-glycoprotein, several apolipoproteins (apo A-I, A-II, A-IV, C-II, C-III, D, E, J), retinol-binding protein, transthyretin and alpha-fetoprotein could be observed. During intrauterine life, the size of the spots corresponding to alpha-fetoprotein progressively decreased, whereas the protein pattern globally showed an increase in the number and in the size of the spots. These modifications were particularly apparent in the regions of the electrophoretograms restricted to the heavy and light chains of IgG and to alpha 1-antichymotrypsin. In addition, we observed an unidentified fetal polypeptide characterized by an apparent molecular weight (M(r)) of 46 kDa (P46) and a pI of 5.0. P46 was present in all fetuses and all infants of less than 2 years of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Clonal imbalances of serum immunoglobulins after allogeneic bone marrow transplantation: an analysis by high-resolution two-dimensional gel electrophoresis.

The clonality pattern of immunoglobulins (Igs) produced after allogeneic bone marrow transplantation (BMT) was studied by high-resolution two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) of serum samples and purified Igs. With this technique, the light (L) chain of a monoclonal Ig usually appears as a single spot. Thus, the degree of clonal diversity of the functional B cells can be appreciated by the electrophoretic pattern of the serum L chains. Furthermore, 2D-PAGE allows a semi-quantitative determination of prominent Ig clones according to the size of L chain spots. We found that serum electrophoretograms of 8/19 patients after BMT (5-9 months) revealed L chain patterns which were similar to those of normal polyclonal Igs, that is, less than five distinguishable small spots among a cloud-like indiscrete L chain spots region ('polyclonal' pattern). A spectrum of clonal abnormalities was observed on the electrophoretograms of 11/19 patients: in five patients, multiple small L chain spots (corresponding to Ig concentrations between 0.2 and 2 g/l) were detected ('oligoclonal' pattern), whereas in six others, 'typical' monoclonal Igs (Ig concentrations > 2 g/l) were observed with (3/19 patients) or without (3/19 patients) multiple small clonal components. Sequential analysis of serum obtained from patients at different times after BMT revealed that imbalanced clonal reconstitution was transient and evolved towards apparently normal polyclonal Ig production. Our observations show that the development of clonal 'gammopathies' after BMT is a frequent, but not obligatory phenomenon. It may reflect a transient restriction of the B cell repertoire either through a limited outgrowth of precursor cells or through selective antigenic pressures.

Antibody Diversity↗
PubMed1992

Monoclonal gammopathy in a 30 weeks old premature infant.

The occurrence of monoclonal gammopathy in childhood is extremely rare. This report describes the presence of a monoclonal immunoglobulin in a 30 week old premature infant, incidentally discovered by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) during an ongoing study of the plasma/serum protein development. Comparative analysis of the electrophoretogram of the infant with 'reference' protein maps revealed the presence of an 'abnormal' immunoglobulin light chain spot. A spot having an identical apparent molecular weight and isoelectric point was also detected after 2D-PAGE of the mother's plasma and its Protein-A purified immunoglobulin fraction. The observation of a monoclonal gammopathy in a premature infant, most likely transmitted from his mother, highlights the potential usefulness of 2D-PAGE in the clinical laboratory.

Blood Protein Electrophoresis↗
PubMed1991

[Infectious fetal diseases. Prevention, prenatal diagnosis, practical measures].

Many congenital infections can produce foetal diseases and are sometimes responsible for major disablements. The most frequent infectious foetal diseases are toxoplasmosis, rubella and chickenpox. Diseases caused by parvovirus or cytomegalovirus are exceptional. Foetal blood sampling has considerably simplified the prenatal diagnosis and made it accessible to more medical centres; it has also widened the therapeutic possibilities and above all, it has considerably reduced the number of therapeutic abortions. It may well be that the development of molecular biology, which has the great advantage of permitting an earlier diagnosis, will in the near future make it possible not only to detect numerous monogenic diseases before birth, but also to diagnose some foetal infections. We might then hope that a much earlier treatment in utero will also be more effective.

Chickenpox↗
PubMed1991

Fetal toxoplasmosis: ultrasonographic signs.

Eighty-nine cases of proven Toxoplasma gondii fetal infection were studied in order to describe the morphological lesions which could be demonstrated on ultrasound examination; these were present in 32 of the infected cases. Cerebral ventricular dilatation was the most common sign and was generally bilateral and symmetrical. Its evolution was always very rapid over a period of a few days. Other signs observed included intracranial and intrahepatic densities, increased thickness and hyperdensity of the placenta, ascites and rarely pericardial and pleural effusions. Thirteen fetuses demonstrated two or more ultrasound features. Intrauterine growth retardation and microcephaly were not observed. Ultrasonographic assessment of the fetus injected with Toxoplasma gondii is important. It improves the reliability of prenatal diagnosis and is of important prognostic value in cases with severe brain lesions, but is of little value in detecting brain necrosis without ventricular dilatation.

Journal Article↗
PubMed1991

Cytomegalovirus fetal infection: prenatal diagnosis.

We report the results of prenatal diagnosis in 15 cases of primary cytomegalovirus infection during pregnancy. Sixteen fetuses (one twin pregnancy) were examined by ultrasonography, amniocentesis, and fetal blood sampling. Prenatal diagnosis was positive in eight cases as evidenced by positive amniotic fluid cultures in eight, positive immunoglobulin M (IgM) in six, and abnormal ultrasound in two. Among infected fetuses, abnormal laboratory findings included anemia, thrombocytopenia, and elevated liver function tests. Three pregnancies were terminated because of ultrasound abnormality or abnormal laboratory indices. In cases of fetal infection with normal ultrasound and normal laboratory findings, the pregnancies were allowed to proceed, leading to the birth of four infants (three with subclinical infections, one with bilateral hearing loss). The relation between anemia, thrombocytopenia, altered liver function tests, and subsequent handicap remains unknown, but the abnormalities observed in utero correspond to those described at birth in cases of cytomegalic inclusion disease. Amniocentesis alone allowed the diagnosis of infection in all cases, but fetal blood sampling provided additional information about the fetal condition.

Cytomegalovirus Infections↗
PubMed1990

[Hematological parameters and prognosis in established or imminent HELLP syndrome. Apropos of 12 case reports].

We describe the clinical and biological characteristics of 12 pregnant women with the HELLP syndrome as defined by Weinstein in 1982 (H for hemolysis, EL for elevated liver enzymes and LP for low platelet count). The data demonstrate that this syndrome is an obstetric emergency threatening the lives of both mother and child. However, if delivery is prompt the prognosis is good. The suspicion of gestosis requires a hematological assessment (complete blood count and close examination of blood film, evaluation of hemostasis) as an essential component in therapeutic decisions.

Adult↗
PubMed1990

Toxoplasma gondii infection during pregnancy: T lymphocyte subpopulations in mothers and fetuses.

Prenatal diagnosis of fetal toxoplasmosis is possible with the use of fetal blood sampling, amniocentesis and ultrasound examination. The purpose of this study was to describe T lymphocyte subsets (CD3, CD4 and CD8) in mothers and their fetuses when Toxoplasma gondii infection occurred during pregnancy. Maternal and fetal blood samples were obtained in 86 cases and 9 fetuses showed T. gondii infection. Control groups consisted of 30 healthy nonpregnant women and 30 pregnant women. Pregnant women with T. gondii infection showed an increase in the suppressor (CD8) T subpopulation and a significant depression in the total helper (CD4) T cells. These alterations were more important in mothers whose fetus was infected. We showed the progressive maturation of the fetal immune system with a regular increase of all T lymphocyte subsets. Marked alterations were observed in the 9 infected fetuses (depression of CD4 population and lower CD4/CD8 ratio). In the future these differences might be used as a new marker of the severity of fetal lesions and become a useful diagnostic tool.

CD4-Positive T-Lymphocytes↗
PubMed1989

Fetal toxoplasmosis: outcome of pregnancy and infant follow-up after in utero treatment.

Eight-nine cases of fetal Toxoplasma infection are reported in women treated with spiramycin during pregnancy. Thirty-four pregnancy terminations were performed (2.7% of the total number of acquired Toxoplasma infections during pregnancy). Fifty-two pregnancies were allowed to proceed (43 being additionally treated with pyrimethamine and sulfonamides), leading to the birth of 54 live infants. After a mean follow-up period of 19 months, 41 infants had evidence of subclinical Toxoplasma infection, 12 had a benign form, and one had severe congenital toxoplasmosis (this infant did not receive the additional treatment during pregnancy). Efficacy of the additional treatment with pyrimethamine and sulfonamides was demonstrated by a significant reduction of severe congenital toxoplasmosis and the relative decrease of the ratio of benign to subclinical forms. We recommended that spiramycin treatment be started as soon as possible once the diagnosis of maternal Toxoplasma infection during pregnancy is proved or strongly suspected, because a prolonged time interval between onset of infection and start of treatment seems to be associated with the presence of severe fetal lesions at the time of prenatal diagnosis.

Female↗
PubMed1989

[Active management of labor. Preliminary results].

Concerned by the raise in cesarean section rate we introduced a more active management of labor derived from the Dublin experience. This involved a more accurate diagnosis of labor, associated with early diagnosis and augmentation of nonprogressive labor by oxytocin. Two groups of patients who delivered before and after the method was applied were compared. Cesarean section rate fell from 29.6% to 21% (p less than 0.01) and the mean duration of labor was reduced by two hours in nulliparas (from 7 h to 5 h: p less than 0.0005) and by one hour 15 minutes in multiparas (from 4 h 15 min to 3 h: p less than 0.0005), without change in the number of forceps deliveries and the perinatal outcome. Our cesarean section rate remains high. This is largely due to the number of high-risk pregnancies (10% preterm deliveries), the percentage of nulliparas (49%) and the systematic abdominal delivery of breech in nulliparas.

Adult↗
PubMedDate not supplied

[Intrauterine transplantation of hematopoietic stem cells for therapy of genetic diseases].

In utero transplantation of hematopoietic stem cells is a most promising fetal therapy. The aim is to treat a genetic disease prenatally before the onset of irreversible organ damage. As the fetus is immunoincompetent in the first and early second trimester of pregnancy and thus tolerant to foreign antigen, engraftment of transplanted stem cells is possible without rejection and without the need for immunosuppression. Additionally, there is enough space available in the fetal bone marrow for the homing of transplanted stem cells, and the intrauterine environment is protective for the fetus, thus typical complications of postnatal transplantation like graft rejection could be avoided. Good results of in utero treatment of severe congenital immunodeficiencies have been achieved in different animal models as well as in humans. No success, however, has been reported as yet in genetic diseases without immunodeficiency, mainly because it seems to be difficult to achieve a clinically significant level of chimerism. Ongoing research projects are focussed on the search for alternative stem cell sources like umbilical cord blood or fetal liver, optimizing the in vitro stem cell processing by using special enrichment techniques, adding early growth factors to the transplant or expanding stem cells ex vivo and finding the ideal stem cell dose. In non-immunodeficient recipients the "window of opportunity" seems to be exclusively at the end of the first trimester; thus early administration of the transplant is mandatory. Induction of tolerance against donor cells is possible, though the clinical relevance for postnatal transplantation remains to be proven.

Animals↗