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Biomedical subjects

Z Pavlova

Publications and source records attributed to Z Pavlova.

At least 19 recordsLinked to original sources

Infection as a cause of death in the extremely-low-birth-weight infant.

OBJECTIVE: To determine the causes of neonatal death for extremely-low-birth-weight (ELBW) infants. METHODS: All liveborn infants below 1000 g birth weight born from 1994 to 1998 who died and were autopsied were included. Maternal and infant characteristics, placental histology, autopsy material and culture results were obtained. RESULTS: A total of 263 ELBW infants were born alive, 104 (40%) died and 44 (42%) were autopsied. Placentas were available for 41 (93%). Infection was the leading cause of death in the autopsied babies (25/44; 57%). Sixteen (64%) of these deaths occurred within the first 48 h and were classified as being due to congenital infections. Twenty-two of 41 (54%) placentas showed evidence of infection. Infection as a cause of death peaked at 22 weeks. Other causes of death were lethal anomalies (20%), respiratory distress and its complications (9%) and immaturity, intraventricular hemorrhage and other conditions (14%). CONCLUSION: Congenital infection is the leading cause of death in ELBW infants.

Autopsy↗

Meconium-stained amniotic fluid and neonatal morbidity in near-term and term deliveries with acute histologic chorioamnionitis and/or funisitis.

OBJECTIVE: To determine the incidence of meconium-stained amniotic fluid (MSAF) and neonatal morbidity in near-term and term deliveries with histologic acute chorioamnionitis and/or funisitis compared to those with normal placental histology. STUDY DESIGN: In a retrospective case-control design, we compared the incidence of MSAF and neonatal outcome in 45 cases of acute histologic chorioamnionitis and/or funisitis with 89 cases of normal placental histology. We reviewed the obstetric and neonatal records for perinatal complications and neonatal morbidity. RESULTS: Mean birthweights (3372+/-473 vs 3287+/-518 g) were similar in infants born to mothers with histologic chorioamnionitis and/or funisitis compared to infants born to mothers with normal placental histology. The incidence of MSAF was significantly higher in the group with acute chorioamnionitis/funisitis (p<0.05). Similarly, the incidence of admissions to newborn intensive care unit, respiratory distress, meconium aspiration syndrome, and presumed sepsis was also significantly higher (p<0.05) in this group. CONCLUSION: The incidence of MSAF and neonatal morbidity is higher in the presence of acute inflammation of placental membranes. The presence of meconium in the amniotic fluid should alert the physician to the potential for infection and increased neonatal morbidity.

Acute Disease↗

Causes of death in the extremely low birth weight infant.

OBJECTIVE: To present primary and secondary causes of death confirmed by autopsy for the extremely low birth weight infant. METHODS: A total of 111 infants weighing between 300 and 1000 g at birth who died and were autopsied at our hospital during the 4-year period 1990-1993 were retrospectively reviewed. Clinical, pathologic, and laboratory data were retrieved including results of placental examinations and autopsy cultures. Primary and secondary causes of death were assigned by the authors. RESULTS: Infection was the most common primary cause (56/111) followed by respiratory distress syndrome/bronchopulmonary dysplasia (24/111) and congenital defect (15/111). Immaturity as an only cause appeared almost exclusively in infants weighing <500 g at birth. Infection was significantly underdiagnosed clinically with most of these deaths attributed to immaturity or respiratory distress syndrome. In only 1 case was intraventricular hemorrhage considered the primary cause of death although it was present as a secondary cause in 19/111. Infections were divided into congenital (30/56) and acquired (26/56) by time of death. The congenital infections (</=48 hours) consisted of pneumonia and chorioamnionitis/funisitis attributable to maternal enteric organisms. Causative bacteria were obtained in pure culture in a number of these cases. The acquired infections were mainly caused by yeasts and nosocomial bacteria. Sixty-seven percent of the deaths occurred in the first 2 days and 12% were beyond the neonatal period at 29 to 104 days. Care was not initiated or was withdrawn in 50% of the infants, usually within the first 4 hours. CONCLUSIONS: Infection of the amniotic fluid leading to pneumonia was the major cause of death in the extremely low birth weight infant. Accurate cause of death can not be reliably ascertained without an autopsy accompanied by examination of the placenta in the early deaths. Antibiotic treatment of the mother and infant may have reduced the deaths from infection. Early failure to respond to neonatal intensive care may well indicate presence of a congenital pneumonia.

Amniotic Fluid↗

The spectrum of pathological changes in the lung in children with the acquired immunodeficiency syndrome: an autopsy study of 36 cases.

We present the pulmonary findings in 36 autopsies of children affected by the acquired immunodeficiency syndrome (AIDS). Twenty-three patients were male and 13 were female, ranging in age between 3 days and 13 years. Twenty children had human immunodeficiency virus (HIV)-positive parents or parents who were at high risk of exposure (intravenous drug abusers and prostitutes), five had a history of transfusion, and one had a history of renal transplantation and blood transfusion. Clinically, the patients presented with recurrent infections, failure to thrive, hepatosplenomegaly, fever, cough, and/or hemoptysis. Histologically, specific infectious processes were the most common finding (75% of cases), with Pneumocystis carinii pneumonia being the most prevalent type of infection, followed by bacterial pneumonia. Neoplastic conditions and lymphoid interstitial pneumonia were less frequent (approximately 10% of cases). In addition, in approximately 10% of the cases the pulmonary findings were non-specific (ie, pulmonary edema and atelectasis) and probably unrelated to HIV infection. Our findings suggest that specific infectious conditions constitute the most common type of pulmonary pathology in children with AIDS. However, because there is a small percentage of children with nonspecific findings, a transbronchial biopsy is important for proper evaluation before institution of therapy.

AIDS-Related Opportunistic Infections↗

Human developing enamel proteins exhibit a sex-linked dimorphism.

The amelogenin protein of developing dental enamel is generally accepted to mediate the regulation of the form and size of the hydroxyapatite crystallites during enamel biomineralization (1). A genetic disorder of enamel development (amelogenesis imperfecta) has been linked to the amelogenin gene AMEL(2-3), and loci regulating enamel thickness and tooth size have been mapped to the human sex chromosomes (4). In the human genome there are two AMEL loci with one copy of the gene on each of the sex chromosomes (AMELX and AMELY), whereas in the mouse only an AMELX locus is present (5). It is presently unknown if human AMELY is transcriptionally active. These observations prompted us to examine specimens of human developing enamel for sexual dimorphism at the protein level. We report here, for the first time, a diagnosis of differences in human enamel proteins which permits the distinction of specimens according to the sex of the individual.

Ameloblasts↗

Dystrophin protein and RFLP analysis for fetal diagnosis and carrier confirmation of Duchenne muscular dystrophy.

A pregnant woman with indeterminate Duchenne muscular dystrophy (DMD) carrier status, but with DMD diagnosed in her deceased brother (unavailable for study), presented for prenatal diagnosis, intending to continue the pregnancy only if proven unaffected with DMD with near absolute certainty. Creatine kinase (CK) assays to clarify carrier status were inconclusive. Male sex in the fetus was identified, but DNA restriction fragment length polymorphism (RFLP) analysis was not yet available to this centre to investigate the possible transmission of the DMD gene, and the pregnancy was terminated. Tissue histology and dystrophin protein analysis demonstrated the absence of DMD. In a situation with proven maternal carrier status, future fetal inheritance of the opposite maternal X chromosome would indicate the presence of DMD. However, maternal carrier status remained in doubt through a second pregnancy, even with RFLP studies, and was finally established when dystrophin analysis confirmed the presence of DMD in the second fetus. Histologic findings are presented, contrasting features in the two fetuses. The value of dystrophin analysis for establishing the diagnosis of fetal DMD, in this case proving maternal carrier status in a difficult situation, and for demonstrating DMD gene:RFLP haplotype relationships is illustrated.

Adult↗

Isolation and partial characterization of a human amelogenin from a single fetal dentition using HPLC techniques.

A strategy based on high pressure liquid chromatography (HPLC) techniques for the isolation or a principal amelogenin molecule from a single human dentition is described. A partial sequence (33 residues) for this 24 kDa amelogenin is presented and related to earlier studies of human 5 kDa tyrosine-rich amelogenin polypeptides (TRAPs). A failure to identify amino acid residue #25 (tryptophan in other amelogenins) suggests that this 24 kDa amelogenin is the progenitor of the human TRAP-2 molecule and provides further support for the possibility of several human amelogenin gene products, generated by splice-junction selection, from the single amelogenin gene in the same individual. Alternatively, multiple amelogenins may arise by expression of both the AMELX and AMELY loci.

Amelogenin↗

The correlation of arterial lesions with umbilical artery Doppler velocimetry in the placentas of small-for-dates pregnancies.

The placentas of 14 growth-retarded fetuses with abnormal umbilical artery velocimetry and 15 appropriately grown fetuses with normal waveforms were collected immediately after delivery and analyzed in a blinded fashion. A large percentage of the arterial vessels in the placentas from the former group showed abnormal changes in the vessel wall. The percentage of abnormal arterial vessels in all placentas correlated significantly with the resistance index. This study provides an anatomical basis for the elevated resistance to blood flow in placentas from growth-retarded fetuses.

Adult↗

Human amelogenins: sequences of "TRAP" molecules.

The extracellular protein matrix of developing enamel includes a major class of proteins, the amelogenins, which are believed to be concerned in regulating enamel biomineralization. Previous studies have shown the amelogenins of the extracellular matrix to be a complex of proline-rich hydrophobic proteins which, it is suggested, arise through posttranslational and postsecretory processing of a primary ameloblast gene product. More recently, it has been shown that the human amelogenin gene is located on both the X and Y chromosomes raising the possibility that polymorphism at the level of the gene may also contribute to the observed complexity of these enamel matrix proteins. To investigate such possible amelogenin polymorphism in developing human dental enamel, individual fractionated by size-exclusion and reversed-phase high pressure liquid chromatography (HPLC). Two tyrosine-rich amelogenin polypeptides (TRAPs) of approximately 5 kDa in size were isolated from an individual human dentition and characterized by automated gas-phase sequencing. These polypeptides were found to be of 42 (TRAP-2) and 44 (TRAP-1) amino acid residues in length; TRAP-2 lacked a carboxy-terminal -Gly-Trp sequence as has previously been described for analogous bovine TRAP molecules. However, residue #25 of the human TRAP-2 sequence was refractory to sequencing, apparently differing from the Trp-25 identified in TRAP-1. These findings suggest (1) two forms of TRAP molecules, differing only by cleavage of a carboxy-terminal dipeptide, are a general feature of human and other mammalian enamel proteins, probably being derived by postsecretory cleavage from the primary extracellular amelogenin; and (2) in human developing enamel four forms of TRAPs may arise either from polymorphism at the level of the gene, or by posttranscriptional alternative splicing of amelogenin mRNAs, coupled with specific post-secretory proteolytic processing.

Amelogenin↗

Small noncleaved follicular center cell lymphoma: Burkitt's and non-Burkitt's variants in the US. II. Pathologic and immunologic features.

The morphologic criteria for the two variants of small noncleaved follicular center cell (SNC FCC) lymphoma in the Lukes-Collins classification, Burkitt's (BL) and non-Burkitt's variants (NBL), were evaluated and related to the results of multiparameter laboratory and clinical studies. Forty-two patients were studied: 25 cases were classified as BL according to World Health Organization (WHO) criteria. Seventeen cases were classified as NBL on the basis of greater variability in nuclear size and shape, more prominent nucleoli, and greater variation in the amount of cytoplasm. Neoplastic follicles were present in three cases of BL and two of NBL, indicating an FCC origin for this lymphoma. Electron microscopic examination confirmed the light microscopic features. Immunoglobulin (Ig) monoclonality, as demonstrated by immunofluorescence (surface Ig) and/or immunoperoxidase staining for cytoplasmic immunoglobulin (CIg), was demonstrated in 21 of 24 (87.5%) of BL and 13 of 16 (71%) of NBL. Clinically, BL presented more frequently in extranodal sites and with gastrointestinal involvement than NBL. Bone marrow involvement was more common in NBL patients. Both groups had advanced stage disease at diagnosis. The median survival was 10.5 months in BL and 7.7 months in NBL. The results of this study indicate that BL and NBL are biologically related variants of SNC FCC lymphoma but have different presentations, which may be clinically significant.

Adolescent↗

Prenatal diagnosis of tuberous sclerosis: the use of fetal echocardiography.

Fetal echocardiography was used to identify a cardiac rhabdomyoma in the second trimester. The combination of this finding with a maternal history of Tuberous Sclerosis allowed the patient and her family to make a more educated decision regarding termination of the pregnancy. Post mortem examination of the fetus confirmed the prenatal findings. This case report demonstrates the importance of ultrasound evaluation of the fetus at risk of recurrence of a genetic syndrome in which one or more anatomical defects might be seen.

Adolescent↗

Clinical manifestations of epidemic neonatal listeriosis.

We report the broad spectrum of clinical manifestations in 23 infants with positive cultures for Listeria monocytogenes who were treated in our hospital during a recent epidemic. The majority of infants (70%) were preterm and none was small for gestational age. Thirteen (56%) had respiratory distress at birth with evidence of congenital pneumonia. Four of the 5 deaths occurred among these infants. Four infants considered healthy after resuscitation developed fever and lethargy within 36 hours after birth. Only one of these infants had evidence of pneumonia. We conclude that congenital pneumonia with respiratory distress at birth is the major cause of mortality and morbidity from L. monocytogenes infection in the neonate.

Adolescent↗

Immunochemical and biochemical studies of human enamel proteins during neonatal development.

The present communication provides descriptions of the developmental, biochemical, and immunological properties of the human enamel extracellular matrix proteins. We report the isolation and partial characterization of the major human enamel proteins, the production of polyclonal antibodies directed against the human enamelins, and a comparison between the immunogenicity of enamelins and amelogenins from human and mouse enamel extracellular matrices. Our results indicate that although enamelins and amelogenins share some epitopes, each one of these proteins appears to invoke a different degree of immunogenicity.

Amelogenin↗

Squamous cells in the maternal pulmonary circulation.

Identification of squamous cells in the maternal pulmonary arterial circulation, either at autopsy or in blood aspirated from a pulmonary artery catheter, is currently regarded as pathognomonic for amniotic fluid embolism. Sixteen pregnant women underwent pulmonary arterial catheterization for a variety of medical indications. Examination of the buffy coat fraction of the distal lumen aspirate resulted in the identification of squamous cells in all cases. Squamous cells were similarly identified in control specimens from 17 nonpregnant patients; however, the difference in cell count between the pregnant and nonpregnant patients was significant. Such cells presumably reflect, in part, bloodstream contamination from sites of venous access. Reliable differentiation of adult from fetal squamous cells is not possible; however, the significant increase in cell count documented in pregnant patients suggests a possible fetal origin for some squamous cells detected during pregnancy. The detection of squamous cells in the pulmonary arterial circulation of pregnant women is not pathognomonic for amniotic fluid embolism. In a critically ill obstetric patient, such a finding should not deter the clinician from a thorough search for other causes of hemodynamic instability.

Cell Count↗

Fetal injury prior to labor: does it happen?

Major advances have been made in the identification and prevention of perinatal factors that lead to long-term handicap or neurologic deficits. When the infant or child exhibits a major handicap, scrutiny of the pregnancy management often occurs in an attempt to define the causal factors. The medical goal of this inquiry is to prevent injuries and, when possible, to eliminate these factors. In the litigious sense, any deviation from optimal, ideal care or any unusual observations, such as unusual or atypical fetal heart rate patterns, are often causally linked to the adverse outcome. There are at least four categories of major fetal injury that probably occur prior to labor. An awareness of, and a diligent search for, details will no doubt clarify the legitimate origins of many so-called birth injuries. Hence the common tendency to fixate on minor deviations and/or deficiencies of labor and delivery management as causing catastrophic injuries will be successfully challenged.

Adult↗

Epidemic perinatal listeriosis at autopsy.

Seven cases of listeriosis identified at perinatal autopsy are described. The cases occurred during the time of a 1985 Los Angeles, California, epidemic of listeriosis from suspected food contamination by Listeria monocytogenes. In only one of seven cases were gross pathologic lesions encountered. Microscopic lesions in six cases consisted of rare, localized microabscesses or granuloma-like lesions in multiple organs and contained histiocytes, monocytes, lymphocytes, and polymorphonuclear leukocytes with variable necrosis. One case had no gross or microscopic findings. Organomegaly was uncommon. The diagnosis was confirmed in three cases by postmortem blood culture. Complete perinatal autopsy is important for confirmation of listeriosis when microbiologic, gross, or microscopic findings alone may not yield characteristic features.

California↗

B cell acute lymphocytic leukemia in adults. Clinical, morphologic, and immunologic findings.

Acute lymphocytic leukemia (ALL) is a heterogeneous group of disorders, clinically, immunologically, and pathologically. ALL of a B cell phenotype (B-ALL) is the least common. We have studied ten adult patients with B-ALL, none of whom had a tumor mass. The median age was 56 years (range, 30 to 90). A history of an altered immune state was noted in four cases: a distant history of Hashimoto's thyroiditis in one, pregnancy in one, and acquired immunodeficiency syndrome in two. Two patients presented with CNS involvement, and in two additional patients CNS leukemia developed during the course of disease. By the French-American-British (FAB) classification system, L3 leukemic morphology was present in nine, whereas L2 was present in one. Circulating leukemic blasts varied from less than 500/dL to greater than 15,000/dL. Eight patients were thrombocytopenic, and eight were anemic at presentation. Immunologic marker studies on leukemic blasts revealed monoclonal kappa light chain marking in nine and monoclonal lambda in one. Following chemotherapy, complete remission was achieved in three patients, two of whom experienced relapse within 9 months. The median survival for the group was 3 months, and only one patient experienced long-term, disease-free survival. We conclude that B-ALL in the adult presents with the classic L3 morphologic picture in the majority and is associated with extremely short survival.

Adult↗

Small noncleaved follicular center cell (FCC) lymphoma: Burkitt and non-Burkitt variants in the United States. I. Clinical features.

With the understanding that Burkitt's lymphoma was of follicular center cell (FCC) derivation, Lukes and Collins classified the tumor, descriptively, as small noncleaved FCC lymphoma. Two subtypes were described: Burkitt and non-Burkitt. Attempting to define the clinicopathologic features of the subtypes, we studied 42 patients: 25 Burkitt and 17 non-Burkitt. Histologically, the Burkitt tumor demonstrated remarkable uniformity of nuclear size and contour, whereas the non-Burkitt variant had greater variability. Immunoglobulin monoclonality was demonstrated in 83% of Burkitt and 81% of non-Burkitt cases. Burkitt patients tended to be younger. Gastrointestinal disease was seen in 15 Burkitt and only four non-Burkitt patients (P less than 0.05). Disseminated disease was found in the majority of both variants. Marrow involvement was demonstrated in 4.5% of Burkitt and 37.5% of non-Burkitt patients (P less than 0.05). Median survival of Burkitt patients was 10.5 months versus 7.7 months in the non-Burkitt group. The authors believe that significant biologic differences between the variants have been demonstrated, which may be of potential value to the clinician.

Adolescent↗