Umbilical Cord Coiling and Zygosity: Is there a Link?

INTRODUCTION: The aim of this study was to analyze abnormalities of umbilical coiling index (UCI) in twin gestation to test whether the coiling is genetically influenced by zygosity. METHODS: Data retrieved comprised gestational age (GA), chorionicity, fetal gender, and UCI. RESULTS: The mean UCI of hypercoiled cords in monochorionic placentas was 0.55 coils/cm and 0.49 coils/cm in dichorionic placentas with discordant fetal gender (P = 0.2629). DISCUSSION: In conclusion, no significant statistical difference between UCI in monochorionic and dichorionic twin placentas with discordant fetal gender was identified, suggesting that zygosity does not play a role in umbilical coiling induction.

Sudden unexpected early neonatal death due to undiagnosed Hirschsprung disease enterocolitis: a report of two cases and literature review.

Hirschsprung enterocolitis (HEC) is an uncommon, albeit well known, complication of Hirschsprung disease (HD). It is multifactorial and can appear in different age groups, but is particularly important in the neonatal period where it is characteristically seen in full-term neonates. Two cases of HEC are reported that were diagnosed at post-mortem examination, which presented as early sudden neonatal death, with a review the literature on fatal Hirschsprung enterocolitis. Case 1 was a 4-day old male neonate who was found unwell, struggling to breath, and with green vomitus. He was taken to hospital and pronounced dead a short time later. According to the parents meconium was passed on the first day. Post-mortem examination demonstrated necrotizing enterocolitis with isolated bowel perforation. Histology disclosed unsuspected HD. Case 2 was a 2-day old male neonate who was found wheezing with green vomitus. He arrived floppy, cyanosed, and in shock at the hospital and died a few hours later. Meconium was not passed, according to the parents. Post-mortem examination revealed necrotizing enterocolitis. There was also recto-sigmoidal aganglionosis and acetylcholinesterase staining confirmed HD. HEC is a multifactorial and sometimes recurrent complication of HD which characteristically develops in full-term neonates. Presentation with early sudden neonatal death is rare but should be considered in the diagnostic work-up of sudden deaths in this age group.

MRI features of perifibrinous deposits in the placenta due to COVID-19.

COVID-19 has been linked to pregnancy complications and loss (1). Infection during pregnancy is usually mild (2). The risk is highest in the third trimester with increased hospital admission rates and maternal and fetal compromise (3). Post-COVID placentitis is uncommon but the effect on the placenta and the fetus is extensive (4). We present a case correlating clinical, imaging, and pathological findings. Case Report: A 29-year-old para 2 gravida 1, with a normal fetal anomaly scan at 22 weeks gestational age (GA) contracted COVID at 24 weeks gestation. Fully recovered but reported reduced fetal movements at 27 weeks and 1 day. Imaging: US scan showed bright echoes within the brain, small lungs, and oligohydramnios. MRI showed abnormal brain signals, small lungs, and oligohydramnios but also a very abnormal placenta. Reduced and heterogeneous T2 signal and a marked reduction in the DWI signal intensity. The placental size was markedly reduced (volume 785.6 cm3 expected for GA is 5604.8-5952.4 cm3. The surface area of attachment was 3220 mm2, expected 22180.4-29293.2 mm2). Pathology: The placenta was small (fifth centile) with massive perivillous fibrin deposition and multifocal chronic deciduitis. Histology revealed placental chorionic villi showing diffuse sclerotic changes surrounded by perivillous fibrin deposition in the intervillous space. The basal plate revealed multifocal chronic deciduitis. When imaging the fetus, it is important to examine the placenta and correlate any abnormalities. The placenta is a forgotten organ and should be routinely included and assessed to allow the detection of important abnormalities.

Why Should Clinical Autopsies Continue to Exist?

At some point in history, medicine was integrated with pathology, more precisely, with pathological anatomy [...].

Beta1 integrin and VEGF expression in an experimental model of brain tissue heterotopia in the lung.

INTRODUCTION: Integrins and vascular endothelial growth factor (VEGF) are crucially involved in interaction, proliferation, migration, and survival of the cells. However, there is no report in the literature about beta1 integrin and VEGF expression in heterotopic brain tissue. PURPOSE: The aim of this study was to assess beta1 integrin and VEGF expression in experimental brain tissue heterotopia in the lung during both fetal and neonatal periods. MATERIALS AND METHODS: Twenty-four pregnant female Swiss mice were used to induce brain tissue heterotopia on the 15th gestational day. Briefly, the brain of one fetus of each dam was extracted, disaggregated, and injected into the right hemithorax of siblings. Six of these fetuses with pulmonary brain tissue implantation were collected on the 18th gestational day (group E18) and six other on the eighth postnatal day (group P8). RESULTS: Immunohistochemistry of the fetal trunks showed implantation of glial fibrillary acidic protein- and neuronal nuclei-positive heterotopic brain tissue, which were also positive for beta1 integrin and VEGF in both groups E18 and P8. CONCLUSION: These results indicate that brain tissue heterotopia during fetal and postnatal period is able to complete integration with the lung tissue as well as to induce vascular proliferation which are the necessary steps for a successful implantation.

Neuronal maturation in an experimental model of brain tissue heterotopia in the lung.

Neural maturation involves diverse interaction and signaling mechanisms that are essential to the development of the nervous system. However, little is known about the development of neurons in heterotopic brain tissue in the lung, a rare abnormality observed in malformed babies and fetuses. The aim of this study was to identify the neurons and to investigate their maturation in experimental brain tissue heterotopia during fetal and neonatal periods. The fetuses from 24 pregnant female Swiss mice were used to induce brain tissue heterotopia on the 15th gestational day. Briefly, the brain of one fetus of each dam was extracted, disaggregated, and injected into the right hemithorax of siblings. Six of these fetuses with pulmonary brain tissue implantation were collected on the 18th gestational day (group E18), and six others were collected on the 8th postnatal day (group P8). The brain of each fetus from dams not submitted to any experimental procedure was collected on the 18th gestational day (group CE18) and on the 8th postnatal day (group CP8) to serve as a control for neuronal quantitation and maturation. Immunohistochemical staining of NeuN was used to assess neuron quantity and maturation. The NeuN labeling index was greater in the postnatal period than in the fetal period for the experimental and control groups (P8 > E18 and CP8 > CE18), although there were fewer neurons in experimental than in control groups (P8 < CP8 and E18 < CE18) (P < 0.005). These results indicate that fetal neuroblasts/neurons not only survive a dramatic event such as mechanical disaggregation, in the same way as it happens in human cases, but also they retain their development in heterotopia, irrespective of local tissue influences.

Infectious diseases in paediatric pathology: experience from a developing country.

Infectious and parasitic diseases have always challenged man. Although many of them are typically seen in some areas of the world and can be adequately managed by just improving socioeconomic status and sanitary conditions, they are still quite prevalent and may sometimes be seen outside their original geographical areas. Human migration due to different reasons, tourism, blood transfusion and solid organ transplantation has created new concerns for health professionals all over the world. If not for diagnostic purposes, at least these tropical and infectious diseases should be largely known because their epidemiology, pathogenesis, host/parasite interaction, inflammatory and reparative responses are quite interesting and teach us about human biology. Curiosity is inherent to pathology practice and so we are compelled to look for things other than tumours or degenerative diseases. This review focuses on infectious and parasitic diseases found in a developing country and brings up-to-date information on diseases caused by viruses (dengue, yellow fever), bacteria (typhoid fever, leprosy), parasites (Chagas' disease, cutaneous and visceral leishmaniasis, amoebiasis, Capillaria hepatica, schistosomiasis, cysticercosis) and caused by fungi (paracoccidioidomycosis, cryptococcosis, histoplasmosis) that may be useful for pathologists when facing somewhat strange cases from developing countries.

Morphological and morphometrical alterations of the osteochondral junction in perinatal necropsies.

Infants who die during the perinatal period could present the following upon examination of the ribs: alterations of the osteochondral junction (OCJ) that could be related to intrauterine growth restriction, placental alterations, maternal disorders, and congenital abnormalities. The aim of this study was to identify the morphological alterations of the OCJ in the autopsied infants and the factors associated with its pathogenesis. The OCJ from 254 infants were sequentially autopsied and analyzed. Hematoxylin-eosin and blue Masson's trichrome stains were used for examination. The expression in the chondrocytes of the cartilage oligomeric matrix protein (COMP) was measured using a polyclonal antibody. There were 199 (78.3%) cases with normal OCJ and 55 (22%) cases with alterations; among these, 38 (14.9%) cases have an increased cartilage matrix at the free bone marrow zone of the OCJ (ICM), 10 (3.9%) cases have a bizarre pattern (BZ), 5 (2%) cases have a bone tissue formation closing de growth channels (MCO) of the OCJ, and 2 (0.8%) cases have bone marrow cells encroaching the free bone marrow zone. The length of the proliferative zone was different in the groups with alterations of the OCJ (P < .001), being higher in the group of patients with MCO and ICM (P < .05). In the group with BZ, the length was smaller (P < .05). The analysis of the OCJ is important in the autopsies performed at the perinatal period, and this study contributes for a better understanding of the mechanisms related to the etiology of these alterations.

Sudden infant death syndrome in Brazil: fact or fancy?

CONTEXT AND OBJECTIVE: The true incidence of sudden infant death syndrome (SIDS) in Brazil is unknown. The aim here was to identify SIDS cases in the city of Ribeirão Preto, State of São Paulo, between 2000 and 2005, in order to estimate its incidence. DESIGN AND SETTING: Retrospective analysis of data on live births and infant deaths in Ribeirão Preto and from autopsies of infants performed at the Death Verification Service of the Interior (SVOI) between 2000 and 2005. RESULTS: There were 47,356 live births and 537 deaths, with infant mortality rates ranging from 12.9 to 10.9 of live births. Among the 24 infants who died possibly due to SIDS and who were autopsied at the SVOI, six were from families living in the municipality (0.13 of live births): three (50%) were diagnosed as SIDS, and one each (16.66%) as indeterminate cause, bronchoaspiration and cerebral edema. Two deaths occurred in the first month of life (33.33%) and one each (16.66%) at two, four, six and eight months. Two deaths each (33.33%) occurred in the months of February and December, one each in August and October (16.66%). Four cases (66.7%) occurred in the summer and one each (16.66%) in winter and spring. There was 5:1 predominance of males over females. CONCLUSIONS: The frequency of SIDS was lower than what has been reported worldwide and in the Brazilian literature, thus suggesting underdiagnosis, indicating the lack of any specific postmortem protocol for SIDS identification and showing the need to implement this.

An experimental study on the effects of ethanol and folic acid deficiency, alone or in combination, on pregnant Swiss mice.

INTRODUCTION: Ethanol is teratogenic, interferes with folic acid and is extensively used by young women. Our objective was to determine the effects of ethanol and/or folate deficiency on mouse fetuses. METHOD: In Experiment 1, pregnant mice receiving a commercial diet were divided into three groups: control (C), low ethanol dose (LE, 0.4 g/kg), and high ethanol dose (HE, 4.0 g/kg). In Experiment 2, pregnant mice receiving a folate-free diet (FFD) were divided into three groups: folate deficiency (FD), folate deficiency plus a low ethanol dose (FDLE), and folate deficiency plus a high ethanol dose (FDHE). Groups C and FD received saline and the remaining groups received ethanol administered i.p. from the 7th to the 9th gestational day (GD) and were sacrificed on the 18th GD. RESULTS: In Experiment 1, Group HE presented congenital anomalies, late fetal death (LFD), lower fetal length and weight and placental weight and diameter than Groups C and LE. In Experiment 2, there was a smaller number of live fetuses, a larger number of reabsorptions and LFD, a smaller length and lower fetal weight, placental weight and diameter in Groups FDLE and FDHE than in Group FD. CONCLUSION: In animals receiving a commercial diet, a high ethanol dose is deleterious to the pregnancy, inducing congenital anomalies, intrauterine growth restriction, reduction of the placenta and increased LFD, events that did not occur with the low dose. However, with a folate free diet, a low ethanol dose is as deleterious as a high dose.

Detection of parvovirus B19 infection in formalin-fixed and paraffin-embedded placenta and fetal tissues.

Parvovirus B19 infection was first discovered in 1975 and it is implicated in fetal death from hydrops fetalis the world over. Diagnosis is usually made through histological identification of the intranuclear inclusion in placenta and fetal organs. However, these cells may be scarce or uncharacteristic, making definitive diagnosis difficult. We analyzed histologically placentas and fetal organs from 34 cases of non-immune hydrops fetalis, stained with Hematoxylin and Eosin (HE) and submitted to immunohistochemistry and polymerase chain reaction (PCR). Of 34 tissue samples, two (5.9%) presented typical intranuclear inclusion in circulating normoblasts seen in Hematoxylin and Eosin stained sections, confirmed by immunohistochemistry and PCR. However, PCR of fetal organs was negative in one case in which the placenta PCR was positive. We concluded that parvovirus B19 infection frequency is similar to the literature and that immunohistochemistry was the best detection method. It is highly specific and sensitive, preserves the morphology and reveals a larger number of positive cells than does HE with the advantage of showing cytoplasmic and nuclear positivity, making it more reliable. Although PCR is more specific and sensitive in fresh or ideally fixed material it is not so in formalin-fixed paraffin-embedded tissues, frequently the only one available in such cases.

Teratogenic effect of retinoic acid in swiss mice.

PURPOSE: To identify the types of malformations resulting from the administration of retinoic acid (RA) to Swiss mice on different days of pregnancy. METHODS: Twenty-four pregnant Swiss mice were divided into 4 groups of 6 animals each. The experimental groups received a single intraperitoneal injection of RA (70 mg/kg) on gestational days 7, 8 and 9 (D7, D8 and D9), while control animals (C) received only saline solution. RESULTS: Were obtained: exencephaly (C:0; D7:16.1%; D8:25.4%; D9:0), myelomeningocele (C:0; D7:25.8%, D8:30.9%, D9:0), spina bifida occulta (C:0, D7:29%, D8:41.8%, D90), gastroschisis (C:0, D7:6.4% D8:5.4%, D9:0), omphalocele (C:0, D7:6.4%, D8:14.5%, D9:0), lower limb alterations (C:0, D7:74.1%, D8:80%, D9:0), imperforated anus (C:0, D7:100%, D8:100%, D9:100%), and tail agenesis/alteration (C: D7:100%, D8:100%, D9:100%). CONCLUSION: The experimental model using Swiss mice proved to be efficient in the induction of the different types of defects, with the eighth gestational day being the one that most favored the induction of neural tube defect, omphalocele, gastroschisis, lower limb defects, imperforated anus and tail agenesis/alteration. On this basis, this is a useful model for future investigation of neural development and of the formation of the appendicular skeleton.

The autopsy in a tertiary teaching hospital in Brazil.

A high autopsy rate allows accurate epidemiological studies and quality control of medical care. This study aims to analyze all autopsies performed in a university teaching hospital in Brazil during 52 consecutive wk. The following data were retrieved from individual autopsy records: gender, age, time of death (hr, day, and month), and the main cause of death. There were 1419 autopsies (79% adults and 21% pediatrics, 60% male and 40% female). Those performed during working days summed up to 67.5%, the remaining 32.5% were performed during weekends or holidays. Autopsies were more frequent during the nocturnal than diurnal period (52.6% vs 47.4%, respectively). The causes of death distributed among the ICD-10 categories were: cardiovascular diseases 21.3%, infectious diseases 19.2%, neoplasms 12.8%, perinatal conditions 10.8%, respiratory diseases 6.6%, gastrointestinal diseases 6.0%, congenital anomalies 4.7%, CNS diseases 3.8%, genitourinary diseases 1.8%, and others 13.0%. There was coexistence of the diseases typical of both industrialized and developing countries, indicating the epidemiological transition in our country. Our data indicate that staff supervision of undergraduate medical students and residents is adequate. Along with a brief discussion of the historical, cultural, and legal factors that allow a high autopsy rate, this study reinforces the importance of the autopsy in a tertiary teaching hospital.

Brain tissue aspiration neural tube defect.

The study aimed to find out how frequent is brain tissue aspiration and if brain tissue heterotopia could be found in the lung of human neural tube defect cases. Histological sections of each lobe of both lungs of 22 fetuses and newborn with neural tube defect were immunostained for glial fibrillary acidic protein (GFAP). There were 15 (68.2%) females and 7 (31.8%) males. Age ranged from 18 to 40 weeks of gestation (mean = 31.8). Ten (45.5%) were stillborn, the same newborn, and 2 (9.1%) were abortuses. Diagnosis were: craniorachischisis (9 cases, 40.9%), anencephaly (8 cases, 36,4%), ruptured occipital encephalocele and rachischisis (2 cases, 9.1% each), and early amniotic band disruption sequence (1 case, 4.5%). Only one case (4.5%) exhibited GFAP positive cells inside bronchioles and alveoli admixed to epithelial amniotic squames. No heterotopic tissue was observed in the lung interstitium. We concluded that aspiration of brain tissue from the amniotic fluid in neural tube defect cases may happen but it is infrequent and heterotopia was not observed.

Adult-type hypolactasia: clinical, morphologic and functional characteristics in Brazilian patients at a university hospital.

BACKGROUND: Adult-type hypolactasia (AH) is the most common form of disaccharidase deficiency in humans, with a prevalence that varies among ethnic groups. In Brazil, the few available studies suggest a high prevalence of this condition. The objective of this study was to determine the prevalence of AH in Brazilian patients at the Ribeirão Preto University Hospital, and to study its morphologic and functional expression. METHODS: One hundred fifteen patients between 5 and 60 years undergoing upper gastrointestinal endoscopy were included. Mucosal biopsy specimens were obtained from the second portion of the duodenum. AH was defined by the disaccharidase activity (lactase/sucrase ratio) of the duodenal mucosa. The morphologic expression of lactase was studied by immunohistochemistry. RESULTS: The mean age of the subjects was 28.8 +/- 14.8 years. Seventy of the 115 subjects (60.8% prevalence) had AH by enzyme activity measurements. Milk drinking was common and similar in patients with and without AH. Among the patients, 91.3% of the nonwhite and 53.2% of the white individuals had hypolactasia (P = 0.002). Immunohistochemistry revealed the presence of lactase in 73.3% of individuals with normal lactase activity. Two different expression patterns were found in patients with AH. CONCLUSIONS: The prevalence of AH was high in our subjects and similar to that reported in other Brazilian studies. Hypolactasia was more common among nonwhites. Immunohistochemistry permitted the identification of two phenotypes of AH, the first characterized by the absence of both stainable lactase and lactase activity, and the second by the presence of stainable lactase without significant activity.

Caudal dysplasia sequence: severe phenotype presenting in offspring of patients with gestational and pregestational diabetes.

The association of maternal diabetes mellitus and congenital anomalies is well established. Children of insulin-dependent diabetic women have an increased risk of congenital malformations, especially major multiorgan defects. The cardiovascular, central nervous, gastrointestinal, genitourinary and musculoskeletal are the most affected body systems. Studies also show that offspring of women with gestational diabetes (specially those with fasting hyperglycaemia) tend to have higher rates of congenital anomalies. We report two cases of infants born to unrelated mothers: one with diabetes mellitus first detected during pregnancy (gestational diabetes) and the other with pregestational diabetes. Both infants had amelia of the lower limbs (suggestive of caudal dysplasia sequence), together with cardiovascular, skeletal, urinary and gastrointestinal defects. While pregestational diabetes seems to leave no doubt about its teratogenicity, the association of gestational diabetes and fetal/newborn malformations is still under discussion. Complete absence of the lower limbs has not been reported in association with gestational diabetes, but it may represent a spectrum of the caudal dysplasia sequence. The presentation of two cases with the same clinical phenotype of mothers with gestational and pregestational diabetes supports the evidence that gestational diabetes can be responsible for the development of the most severe form of the caudal dysplasia sequence.

Phakomatous choristoma of the orbit.

Phakomatous choristoma is a rare adnexal congenital tumor of lenticular anlage. The authors performed a standard orbital tomography of the orbits for the evaluation of a mass that was palpable in the left lower eyelid of a 3-month-old boy. Hematoxylin-eosin, special stainings and immunohistochemistry were performed on the excised mass. The histopathological and immunohistochemical findings confirmed the diagnosis of phakomatous choristoma. The CT scans showed that the mass was located in the orbit. Even though phakomatous choristoma is usually reported as a lower eyelid lesion, the orbital localization offers a better explanation for the chronological embryonic origin of this rare pediatric tumor.

Enamel hypoplasia in a litter of rats with alloxan-induced diabetes mellitus.

Enamel hypoplasia is an important clinical problem commonly seen in children born to diabetic women. We aimed to characterize the enamel hypoplasia in Wistar rats born to alloxan-induced diabetes mellitus rats. Groups consisted of pregnant rats supplemented (ISDR) or not (NISDR) with insulin and controls, in which sterile saline solution was administered instead of alloxan or insulin. The mandibular incisors of one-month-old rats born to these mothers were analyzed. Whitish defective enamel was found macroscopically in both experimental groups (ISDR = 37.5%, NISDR = 33.3%) but not in the control group. Mild to severe enamel hypoplasia was observed by scanning electron microscopy (ISDR = 93.8%; NISDR = 100%, control = 4.2%). The severity of hypoplasia correlated positively with the maternal level of blood glucose. In conclusion, the intensity of enamel hypoplasia in the teeth of the litter born to alloxan-induced diabetic rats was variable and was dependent on the glycemic level of the pregnant rat.

[Assessment of educational objectives in two different curricular structures--Faculty of Medicine of Ribeiráo Preto, University of São Paulo, Brazil]. / Análise do desempenho dos formandos em relação a objetivos educacionais da Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, em duas estruturas curriculares distintas.

OBJECTIVE: The objective of the study was to assess the impact of the curricular change on the achievement of the educational objectives of the institution, analyzing the performance of graduating students, from the Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil. METHODS: Techniques of recognized validity and reliability (MCQ, OSCE, PMP) were used for the evaluation of skills and competence in the cognitive, psychomotor and clinical domains. Three of the 3 final years classes educated according to the previous curricular structure (n=222) and three classes educated according to the new curricular structure (n=261) were evaluated during the study period. RESULTS: The performance of graduating students in these different tests permitted us to estimate the extent of achievement of 17 of the 36 intermediate educational objectives of the institution in the two curricular structures. Comparison of the two curricula demonstrated the absence of significant differences in the extent of achievement of ten of the 17 objectives. For six of the seven remaining objectives a significant increase (p<0.05) in the extent of achievement was observed with the new curricular structure. CONCLUSIONS. The results indicate that the new curricular structure was associated with a better performance of the students in cognitive skills related to general practice and in basic clinical and psychomotor skills.