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Biomedical subjects

C Sergi

Publications and source records attributed to C Sergi.

At least 19 recordsLinked to original sources

Pregnancy outcomes in women with or without placental malaria infection.

OBJECTIVE: To assess delivery outcomes in women with placental malaria who presented at public hospitals in Kisumu, a holoendemic region in western Kenya. METHODS: A cross-sectional study using both histology and molecular biology was conducted with 90 consecutive pregnant women who presented at 3 hospitals during a 2-week period. Data collectors completed standardized questionnaires using each patient's hospital record and physical examination results, and registered birth indices such as weight, head circumference, and weight-head ratio. Malaria infection of the placenta was assessed using a molecular biology approach (for genomic differences among parasite species) as well as histology techniques. Of the 5 histologic classes of placental infection, class 1 corresponds to active infection and class 4 to past infection; class 2 and 3 to active chronic infection; and class 5 to uninfected individuals. Plasmodium species typing was determined by polymerase chain reaction amplification of the parasite's genome. RESULTS: In newborns at term, low birth weight was directly associated with classes 2 and 4 of placental infection (P = 0.053 and P = 0.003, respectively), and differences in birth weight remained significant between the 5 classes (P < 0.001) even after adjusting for parity and mother's age. Plasmodium falciparum was the only detected parasite. CONCLUSIONS: In Kisumu, infection with P. falciparum is an important cause of low birth weight and morbidity when it is associated with histologic classes 2 and 4 of placental infection. Moreover, polymerase chain reaction assays should be supported by ministries of health as an ancillary method of collecting data for malaria control during pregnancy and providing a baseline for future interventions.

Adolescent↗

First localization and biochemical identification of chromogranin B- and secretoneurin-like immunoreactivity in the fetal human vagal/nucleus solitary complex.

The human vagal/nucleus solitary complex is a primary visceral relay station and an integrative brain stem area which displays a high density of chromogranin B- and secretoneurin-like immunoreactivity. In this study, we localized and biochemically identified these proteins during prenatal development. At prenatal week 11, 15, 20 and 37, we performed a chromatographic analysis to identify the molecular forms of PE-11, a peptide within the chromogranin B sequence, and secretoneurin, a peptide within secretogranin II. Their localization was studied with immunocytochemistry, and was compared to that of substance P which is well established as a functional neuropeptide in the vagal/nucleus solitary complex. At prenatal week 11, chromogranin B-, secretoneurin- and substance P-like immunoreactivities were detected consisting of varicosities, varicose fibers and single cells. At the same time, PE-11 and secretoneurin appeared as a single peak in chromatographic analysis. Prohormone convertases PC1- and PC2-like immunoreactivities were also present at week 11. In general, the density for each peptide increased during later fetal stages with the highest density at week 37. These results demonstrate that each chromogranin peptide is expressed during human fetal life in neurons of the vagal/nucleus solitary complex indicating that these peptides could be important during prenatal development.

Chromogranin B↗

DMBT1 expression and glycosylation during the adenoma-carcinoma sequence in colorectal cancer.

The gene DMBT1 (deleted in malignant brain tumour-1) has been proposed to play a role in brain and epithelial cancer, but shows unusual features for a classical tumour-suppressor gene. On the one hand, DMBT1 has been linked to mucosal protection, whereas, on the other, it potentially plays a role in epithelial differentiation. Thus its function in a particular tissue is of mechanistic importance for its role in cancer. Because the former function requires secretion to the lumen and the latter function may depend on its presence in the extracellular matrix, we decided to investigate DMBT1 expression, location and its mode of secretion during malignant transformation in colorectal cancer. Using human colorectal PC/AA cell lines and tissue sections from individual patients, we have examined the expression of DMBT1 and its glycosylation in the adenoma-carcinoma sequence leading to the adenocarcinoma phenotype.

Adenocarcinoma↗

[Growth and differentiation factor 5 (GDF-5) composite improves the healing of necrosis of the femoral head in a sheep model. Analysis of an animal model].

MATERIALS AND METHODS: After creation of necrosis in 23 sheep, the composites were implanted in half of the animals. The animals were sacrificed 6 and 12 weeks after implantation and the femora were harvested. The specimens were investigated by microradiography, computed tomography, and histologically. RESULTS: The GDF-5 composites were effective in the necrosis model. Osseous regeneration of the necrosis and the drill track were accelerated and enhanced by the composites. In treated animals the necrosis was nearly healed and the drill track was filled with bone after 12 weeks. In the control group the track was partially filled with fibrous tissue and necrotic lesions were still present. Specific side effects of the growth factor or the matrix were not documented. This was documented by histological scoring and CT investigation. DISCUSSION: The application of an absorbable GDF-5 composite in combination with a core decompression procedure may enhance the healing of devitalized bone defects and is a promising approach for further studies.

Animals↗

Induction chemotherapy to weekly paclitaxel concurrent with curative radiotherapy in stage IV (M0) unresectable head and neck squamous cell carcinoma: a dose escalation study.

The purpose was to determine the maximum tolerated dose (MTD) of weekly paclitaxel with concurrent, daily irradiation in patients with unresectable head and neck squamous cell carcinoma previously submitted to induction chemotherapy. Patients with stage IV, and unresectable tumor and/or node/s were enrolled. Nine male patients were submitted to a course of paclitaxel 175 mg/m2 day 1 and cisplatin 75 mg/m2 day 2 given every 3 weeks for three courses. Curative radiotherapy (RT) started 3 weeks after the last cycle of chemotherapy with the goal of delivering a total dose of 66-70 Gy. During RT weekly paclitaxel was administered for 6 courses if feasible; paclitaxel was given according to a dose escalation schema in cohorts of three patients. Dose level A, 30 mg/m2; dose level B, 40 mg/m2; dose level C, 50 mg/m2. During weekly paclitaxel the major toxicity was mucositis that required a treatment break in two of three patients in dose level C; mucositis grade 4 required interruption of paclitaxel administration in all these patients. RT can be given in a continuous fashion with weekly paclitaxel after induction chemotherapy. The MTD of weekly paclitaxel was 40 mg/m2.

Aged↗

Molecular pathology and genetics of congenital hepatorenal fibrocystic syndromes.

The hepatorenal fibrocystic (HRFC) syndromes are a heterogeneous group of severe monogenic conditions that may be detected before birth. Commonly, HRFC syndromes present in the neonatal and paediatric age, with consistent developmental abnormalities mostly involving the liver and kidney. The changes include the proliferation and dilatation of epithelial ducts in these tissues with abnormal deposition of extracellular matrix. In this review, we examine the clinical features and differential diagnoses of this group of syndromes, including autosomal recessive polycystic kidney disease (ARPKD), juvenile nephronophthisis (NPHP), Meckel-Gruber syndrome (MKS), Bardet-Biedl syndrome (BBS), and Jeune asphyxiating thoracic dystrophy (JATD). Extrahepatic manifestations include mostly bone and central nervous system abnormalities, dysmorphic features, and developmental delay. Previously, it has been suggested that ARPKD, JATD, and Ellis-van Creveld syndrome (EvC) may arise from defects in differentiation in a common developmental pathway. We review recent molecular advances in the recessive HRFC syndromes and discuss this hypothesis.

Animals↗

A new animal model of femoral head necrosis induced by intraosseous injection of ethanol.

There is no reliable animal model of the early stages of osteonecrosis of the femoral head (ONFH) for the evaluation of new therapeutic approaches. In this study, we propose a new animal model of femoral head osteonecrosis. Pure ethanol was injected into the centre of the femoral head in adult Merino sheep under fluoroscopic control. After 3, 6 and 12 weeks the animals were killed and the femoral heads were harvested. Microradiographic and histological changes were analysed and recorded. Partial necrosis was documented over a period of 12 weeks in all animals. The appearance of necrosis in combination with intact macrotexture, macrocirculation and joint cartilage is similar to the features described in early ONFH in humans. Due to its efficacy and its similarity to the early stages of ONFH in humans, this model may be suitable to evaluate new therapeutic techniques in the treatment of ONFH.

Animals↗

Perinatal hypophosphatasia: radiology, pathology and molecular biology studies in a family harboring a splicing mutation (648+1A) and a novel missense mutation (N400S) in the tissue-nonspecific alkaline phosphatase (TNSALP) gene.

We report on a postmortem diagnosis of perinatal lethal hypophosphatasia, an inborn error of metabolism characterized by a liver/bone/kidney alkaline phosphatase (ALP)-related defective bone mineralization due to mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) gene. Radiological and pathological studies identified a perinatal lethal hypophosphatasia showing a generalized bone mineralization defect including asymmetry of the cervical vertebral arches in a 22 +4 weeks' gestation fetus. Both parents revealed low serum ALP activities supporting the diagnosis. Sequencing analysis of the TNSALP gene showed two heterozygous mutations, 648+1A, a mutation affecting the donor splice site in exon 6, and N400S, a novel missense mutation in exon 11, located near the active site and very close to histidins 364 and 437, two crucial residues of the active site. Sequencing of exons 6 and 11 in the parents showed that 648+1A was from maternal origin and N400S from paternal origin. DNA-based prenatal testing in the subsequent pregnancy following a chorionic villous sampling performed at 10 weeks of gestation showed no mutation and a healthy infant was born at term.

Alkaline Phosphatase↗

Ellis-van Creveld syndrome: a generalized dysplasia of enchondral ossification.

We report a 25-week fetus with lethal Ellis-van Creveld syndrome who was diagnosed prenatally from the US detection of a narrow chest, postaxial polydactyly of the hands, short acro-/mesomelic limbs and a ventricular septal defect. The postnatal radiographic features of the skeleton confirmed the diagnosis. Literature review of the histopathology of the physeal growth plate is contradictory, varying between retardation of the hypertrophic chondrocytes without disorganization and marked disorganization of the proliferating chondrocytes. We investigated numerous sites of the enchondral ossification and observed retardation of the physeal growth plate in all sites and retardation with pronounced disorganization of the physeal growth plate in the upper mesomelic bone segments only. These data support the concept that Ellis-van Creveld syndrome is mainly a generalized disorder of the maturation of enchondral ossification.

Adult↗

Prenatal diagnosis and fetal pathology in a Turkish family harboring a novel nonsense mutation in the lysosomal alpha-N-acetyl-neuraminidase (sialidase) gene.

We report a Turkish family with parental consanguinity and at risk for sialidosis type II, an inherited autosomal recessive disorder caused by lysosomal alpha-N-acetyl-neuraminidase (sialidase, NEU1) deficiency. The proband was a premature male infant that presented with hydrops, hepatomegaly, respiratory distress syndrome, and anemia and that died of respiratory insufficiency 2 months after birth despite intensive care. An abnormally increased [14C]methylamine incorporation and an isolated deficiency of lysosomal alpha-N-acetyl-neuraminidase were found in cultured skin fibroblasts. A previous pregnancy of the mother terminated in a spontaneous abortion in the 13th week of gestation. A successive pregnancy showed hydrops fetalis, and an enzymatic assay of cultured amniotic fluid cells indicated a deficiency of alpha-N-acetyl-neuraminidase. Following pregnancy termination at 20 weeks gestation, light microscopy of fetal tissues revealed classic vacuolation not only in liver, bone marrow, brain, and kidney, but also in endocrine organs such as the thyroid gland, adrenal gland, hypophysis, and testes, and in the thymus. DNA analysis of the family showed that both the proband and the third sibling had a novel homozygous nonsense point mutation at nucleotide 87 in exon 1 of the alpha-N-acetyl-neuraminidase (neu1) gene causing a substitution of tryptophan at codon 29 by a termination codon (W29X). DNA sequencing of polymerase chain reaction products identified the parents as heterozygous carriers. To detect neu1 mRNA expression, a real-time reverse transcription/polymerase chain reaction was performed, and similar rates of neu1 mRNA expression were found in the fibroblasts of the fetus, the 2nd sibling, and in controls. The very early termination codon with complete loss of neuraminidase activity is probably the molecular basis of the unusually severe vacuolation pattern in this form of congenital sialidosis.

Abnormalities, Multiple↗

Accessory liver in an infant with congenital diaphragmatic hernia.

Incidence of congenital diaphragmatic hernia (CDH) ranges from 1 in 2,400 to one in 5,000 live births. Associated anomalies in CDH are approximately 30% to 35%. The authors report on an infant with CDH and an accessory supradiaphragmatic liver with separate vascularization from the thoracic aorta. The pathogenesis of this malformation is discussed. The postoperative course and the follow-up of the child over 5 years was completely uneventful.

Abnormalities, Multiple↗

Restrictive dermopathy: case report, subject review with Kaplan-Meier analysis, and differential diagnosis of the lethal congenital contractural syndromes.

We report on a 34-week-old infant with restrictive dermopathy (RD), a rare lethal genodermatosis, characterized by an abnormal skin growth and differentiation with thin, tightly adherent skin that causes a dysmorphic face, generalized flexion joint contractures, and respiratory insufficiency. Kaplan-Meier analysis of 32 previously well-described infants affected with RD showed a median survival of 132 hours. Lethal congenital contractural syndromes, including Pena-Shokeir phenotype, cerebro-oculo facio-skeletal syndrome, and lethal multiple pterygium syndrome, should be considered first in the differential diagnosis. Other lethal contractural syndromes are discussed.

Contracture↗

Hepatic failure with neonatal tissue siderosis of hemochromatotic type in an infant presenting with meconium ileus. Case report and differential diagnosis of the perinatal iron storage disorders.

We report on a female preterm infant with hepatic failure and neonatal tissue siderosis of hemochromatotic type diagnosed by using both histochemistry and atomic absorption spectroscopy. The infant presented with meconium ileus, signs of rapidly progressive hepatic failure, and hyperferritinemia (7132 ng/ml). Despite surgery and intensive care the infant died 32 days after birth. Postmortem examination showed a wrinkled liver with extensive collapse of the hepatic architecture and regenerating nodules as well as hepatic and extrahepatic iron accumulation of hemochromatotic type, sparing the reticuloendothelial system. Atomic absorption spectroscopy confirmed an increase in the iron content of various organs: liver, heart, pancreas, oral salivary gland, kidney, and adrenal gland. The increase in the iron content of various organs was determined by comparing the analysis of the propositus with those of 5 gestationally age-related preterm infants who had died in the intensive care unit: 2 died of meconium aspiration syndrome, the other 3 of hyaline membrane disease, bronchopulmonary dysplasia, and immaturity, respectively. We also compared the analysis of 15 fetuses having a a condition predisposing to iron accumulation (trisomy 21, trisomy 18, cytomegalovirus, amnion infection syndrome, Rhesus- and ABO-incompatibility, congenital hemolysis, anti-phospholipid syndrome, congenital heart disease). Delta F508, the most frequent mutation seen in cystic fibrosis patients, was excluded by gene sequencing. Different noxae causing iron accumulation in the neonatal period have led to the statement that neonatal hemochromatosis may collect different etiologies, such as metabolic disorders, infections, chromosomal aberrations, and immunological disorders. In this study, we report the singular evidence of neonatal iron accumulation of hemochromatotic type in an infant presenting with meconium ileus and propose a classification of the neonatal disorders associated with iron accumulation.

DNA↗

Bone morphogenetic protein-2 and growth and differentiation factor-5 enhance the healing of necrotic bone in a sheep model.

INTRODUCTION: Osteotropic growth factors enhance bone repair, but their efficacy in an area of necrotic bone is not known. The purpose of this study was to investigate the effects and potential side effects of an intraosseous application of absorbable bone morphogenetic protein-2 (BMP-2) and growth and differentiation factor-5 (GDF-5) composites in a sheep model for partial necrosis of the femoral head. MATERIALS AND METHODS: The direct injection of ethanol under fluoroscopy into the superior centre of the right femoral head produced histologically documentable necrosis of the central region of the head in a previous study of ten sheep. Another 27 sheep constituted the sample to study the effects of BMP-2 and GDF-5. Necrosis was produced in the same fashion in these animals. Four weeks later nine sheep received 300 microg recombinant BMP-2 and nine sheep 300 microg recombinant GDF-5 on an absorbable carrier by surgical implantation. Nine sheep received the carrier alone (control group). The animals were sacrificed at 3, 6, and 12 weeks after implantation and both femora were harvested. RESULTS: Bone density analysis and microscopic examination indicated that bone formation was noticeably induced as early as 3 weeks postoperatively in the growth factor treated animals. Bone regeneration was enhanced by growth factor composites. This was documented by histological scoring and histomorphometric analysis. No severe local side effects secondary to the growth factors, such as heterotopic ossification or inflammation, were observed in either group. DISCUSSION: The application of an absorbable growth factor composite in combination with established surgical techniques is a promising approach, that may enhance the healing of devitalised bone defects. Based on these results, further studies regarding biodegradation, dosage of the protein and surgical technique are required.

Animals↗

Mapping a method for systematically reviewing the medical literature: a helpful checklist postmortem protocol of human immunodeficiency virus (HIV)-related pathology in childhood.

INTRODUCTION: Since the first description of two children affected with human immunodeficiency virus (HIV), various diagnostic procedures have been established. However, the morphologic study of biopsy and autopsy material from children with acquired immunodeficiency syndrome (AIDS) is still of fundamental importance. The morphology has contributed remarkably to the progress in understanding the pathogenesis of the primary tissue lesions and of the sequelae directly or indirectly associated with HIV infection. The aim of this study was to evaluate the HIV pathology in pediatric AIDS (PAIDS) through a systematic review of the English-language literature and to draw up a practical checklist protocol for the postmortem. MATERIALS AND METHODS: Information on HIV pathology in childhood was retrieved from a MEDLINE search (January 1994-January 2001) of the original reports and bibliographic article reviews published in English. Citations from papers retrieved were screened and retrieved papers were evaluated. RESULTS: Based on the screened data, we propose a practical, organ-oriented checklist protocol for the postmortem according to the HIV pathogenesis. CONCLUSIONS: Evidence-based medicine is a paradigm now exerting increasing influence in related fields such as surgery, general practice, psychiatry, and pathology. This article is a summary of the literature on PAIDS pathology. The protocol that we propose is particularly useful for pediatric pathology programs and for electronic data processing.

Acquired Immunodeficiency Syndrome↗

Central nervous system in twin reversed arterial perfusion sequence with special reference to examination of the brain in acardius anceps.

The twin-reversed arterial perfusion (TRAP) sequence, or acardia, is the most severe complication in monozygotic twinning. Although more than 400 cases with TRAP sequence were reported since 1533, thorough investigations of the brain in those cases with a rudimentary head remained infrequent. We report a TRAP sequence with microcephaly and a severely rudimentary brain anlage. Neuropathologic examination clearly demonstrated two types of change: (1) developmental arrest of brain at the prosencephalic stage (holoprosencephaly), and (2) hypoxic damage to the holospheric brain mantle with cystic change (hydranencephaly). With reference to previous studies in experimental animals showing that lack of oxygen during early embryogenesis can induce severe disruptions of head-brain and heart formation, it is concluded that oxygen deficiency due to TRAP may be responsible not only for the encephaloclastic changes in the acardius anceps, but for the developmental arrest of the brain cases as well. This would make it unnecessary to postulate additional primary causes such as asymmetric zygote cleavage (Schwalbe, '07) for the maldevelopment.

Abnormalities, Multiple↗

Stage IIa cervix carcinoma with metastasis to the heart: report of a case with immunohistochemistry, flow cytometry, and virology findings.

OBJECTIVE: The aim of this study was to report a stage IIa squamous cell cervix carcinoma with intraperitoneal carcinomatosis and metastasis to the heart in a 50-year-old woman and to study the original tumor for expression of oncogenes and tumor suppressor gene proteins, for DNA ploidy, and for human papillomavirus (HPV) infection. METHODS: Clinical course, histopathology of the original tumor, and autopsy record were rewieved. The original tumor was analyzed for expression of CD44 variant 6, p16, p21, p53, retinoblastoma (Rb), and c-erb-2. DNA flow cytometry was performed on tissue samples from the original tumor and from the heart. Sequences of the HPV genome on cervical and cardiac tissue samples were amplified by polymerase chain reaction. RESULTS: Immunohistochemical analysis showed expression of CD44v6 and p16. No expression of p21, Rb, c-erb-B2, and p53 was seen. DNA flow cytometry of the original cervical tumor showed a DNA index (DI) of 1.0. DNA flow cytometry of tissue samples from the posterior wall and from the right ventricle of the heart showed two different aneuploid cell populations with DI of 1.6 and 2.2, respectively. HPV gene sequences were identified neither in the original tumor nor in the heart. CONCLUSIONS: To our knowledge, this is the first case of cervix carcinoma with metastasis to the heart with immunohistochemistry, flow cytometry, and virology findings.

Carcinoma, Squamous Cell↗