ABSTRACT
Fetal cardiac defects leading to intrauterine cardiac failure and subsequent fetal hydrops are rare. We report an unusual case of a double-chamber right ventricle leading to progressive fetal cardiac insufficiency and hydrops. The patient was first managed conservatively. Delivery by Cesarean section was performed for a pathological fetal heart-rate tracing at 28 weeks of gestation. The newborn died 4 h postpartum due to generalized cardiac insufficiency.
Subject(s)
Cardiac Output, Low/diagnostic imaging , Fetal Heart/abnormalities , Ultrasonography, Prenatal/methods , Adult , Fatal Outcome , Female , Fetal Heart/diagnostic imaging , Heart Ventricles/abnormalities , Heart Ventricles/diagnostic imaging , Humans , Hydrops Fetalis/diagnostic imaging , Infant, Newborn , Pregnancy , Ultrasonography, Doppler, Color/methodsABSTRACT
OBJECTIVES: Careful investigation of hydrops fetalis (HF) is important with regard to genetic counselling and prenatal diagnosis. HF is known to be associated with various genetic disorders. To date there has been only one report of a male fetus in whom incontinentia pigmenti (IP) was associated with generalised oedema. We describe a family who had a girl with clinical signs of IP after three consecutive miscarriages of three male fetuses due to HF. RESULTS: Molecular genetic analysis showed a mutation in the NEMO/IKK(chi) gene in the girl and the mother, which confirmed the diagnosis of IP in both cases. In the two fetuses that could be investigated, inheritance of the affected maternal X chromosome could be demonstrated retrospectively by linkage analysis. CONCLUSION: The present findings suggest that IP might be an X-linked dominant trait causing HF in male fetuses. In cases of recurrent HF in male fetuses, minimal signs of IP in the maternal line should therefore be carefully investigated in order to be able to perform mutational analysis and to offer appropriate genetic counselling.
Subject(s)
Hydrops Fetalis/genetics , Incontinentia Pigmenti/genetics , Abortion, Spontaneous/genetics , Adult , DNA Mutational Analysis , Female , Genetic Counseling , Genetic Linkage , Humans , I-kappa B Kinase , Male , Mutation , Pedigree , Pregnancy , Pregnancy Complications , Protein Serine-Threonine Kinases/genetics , X ChromosomeABSTRACT
OBJECTIVE: Fetal intrauterine exposure to proinflammatory cytokines present in amniotic fluid has been associated with an increased risk of chronic lung disease. However, the impact of histologically confirmed chorioamnionitis on the fetal lung has not yet been elucidated. We therefore investigated cellular immune response, cell proliferation, and messenger ribonucleic acid cytokine expression in fetal pulmonary tissue in the presence or absence of chorioamnionitis. STUDY DESIGN: Serial tissue sections were obtained from 27 fetuses at the time of autopsy. Three mothers had received antibiotics for treatment of clinical chorioamnionitis before abortion. Immunohistochemical staining of lung tissue comprised lineage-specific markers (CD68(+), CD3(+), neutrophil elastase). Positively stained cells were evaluated with a graticule, and cells per 5 mm(2) were counted. We undertook in situ hybridization to assess the expression of interleukin 8 messenger ribonucleic acid in the fetal lung. RESULTS: Seven of 27 fetuses had been exposed to chorioamnionitis. Fetal lungs showed a marked increase in the presence of histologically confirmed chorioamnionitis in densities of CD68(+) macrophages (68 vs 9.5 cells/5 mm(2), median group vs control group; P =.02) and lymphocytes (7 vs 2.5 cells/5 mm(2), median chorioamnionitis vs control group; P =.05) and a similar but lesser increase in neutrophil density (16 vs 4 cells/5 mm(2); difference not significant). Interleukin 8 messenger ribonucleic acid was expressed in 4 of 6 tissue specimens investigated in the chorioamnionitis group. Exposure to chorioamnionitis resulted in interleukin 8 messenger ribonucleic acid expression 7-fold higher than in the nonchorioamnionitis group; however, this difference did not achieve statistical significance. CONCLUSION: Chorioamnionitis was associated with an intrauterine inflammatory response of the fetal lung characterized by a severe infiltration of macrophages, neutrophils, and lymphocytes and also by an increased expression of interleukin 8 messenger ribonucleic acid.
Subject(s)
Chorioamnionitis/complications , Fetal Diseases/etiology , Lung Diseases/etiology , Antigens, CD/analysis , Antigens, Differentiation, Myelomonocytic/analysis , CD3 Complex/analysis , Chorioamnionitis/diagnosis , Chorioamnionitis/pathology , Female , Fetal Death/etiology , Fetal Diseases/immunology , Fetal Diseases/pathology , Humans , Immunohistochemistry , In Situ Hybridization , Interleukin-8/genetics , Leukocyte Elastase/analysis , Lung/embryology , Lung/immunology , Lung/pathology , Lung Diseases/immunology , Lung Diseases/pathology , Lymphocytes/immunology , Lymphocytes/pathology , Macrophages/immunology , Macrophages/pathology , Neutrophils/immunology , Neutrophils/pathology , Placenta/pathology , Pregnancy , RNA, Messenger/analysisABSTRACT
BACKGROUND: The great majority of reports dealing with human cyclopia and synophthalmia are derived from fetuses at the end of pregnancy. Thus, data concerning early organization of the ocular anlage in this impressive ocular developmental anomaly are almost completely lacking. We therefore present a 12 week-old synophthalmic fetus. CASE REPORT: After uneventful pregnancy spontaneous abortion occurred. Within the face of the hypotrophic fetus there was a central pigmented ocular anlage with an inferior fissure. A nose (proboscis) was not discernible. Histologically, there were two vesicles caudally which fused to one vesicle cranially. Differentiation was more advanced in the anterior and temporal parts of the anlagen. A coherent inner layer (of the optic cup) was not developed. Trisomy 13 was suspected but could not be proved by FISH-technique. CONCLUSIONS: The fetus demonstrates that fusion of the ocular anlagen is finished at the end of the third gestational month and that synophthalmia/cyclopia is very likely to be associated with maldevelopment of the optic cup. As far as we know there is evidence for the first time that organization of the anlagen improves not only in the posterior to anterior and in the medial to lateral but also in the cranial to caudal direction.
Subject(s)
Abnormalities, Severe Teratoid/pathology , Eye Abnormalities/pathology , Fetus/abnormalities , Abnormalities, Severe Teratoid/genetics , Abortion, Spontaneous , Chromosomes, Human, Pair 13/genetics , Eye Abnormalities/genetics , Female , Humans , In Situ Hybridization, Fluorescence , Pregnancy , Pregnancy Trimester, First , Trisomy/geneticsABSTRACT
We present an unusual case of monosomy 17p13-pter and monosomy Xp22.2-pter due to a dicentric translocation chromosome X/17 in a female newborn with severe anomalies. The karyotype was identified as 45,X,dic(X;17)(p22.2;p13) by high resolution GTG banding in lymphocytes. R banding showed the translocational X-chromosome to be late replicating, and there was no spreading of X-inactivation onto the autosomal segment. Furthermore, it could be demonstrated by C banding that the X-centromere in the translocation chromosome was inactive. The results of short tandem repeat (STR) typing confirmed the partial monosomy X and 17 as well as the paternal origin of the two chromosomes X and 17 which were involved in the translocation chromosome formation. The cell stage of the structural rearrangement was consistent with paternal meiosis as well as with postzygotic mitosis. The monosomy was confirmed in lymphocytes and fibroblasts, and mosaicism was not detected.
Subject(s)
Chromosomes, Human, Pair 17 , Monosomy , Translocation, Genetic , X Chromosome , Chromosome Banding , Female , Humans , Infant, Newborn , KaryotypingABSTRACT
Restrictive dermopathy (RD) is a lethal autosomal recessive genodermatosis (MIM No. 275210) in which tautness of the skin causes fetal akinesia or hypokinesia deformation sequence (FADS). Polyhydramnios with reduced fetal movements is followed by premature delivery at around 31 weeks gestation. Manifestations include a tightly adherent, thin, translucent skin with prominent vessels, typical facial changes, generalized joint contractures, enlarged fontanelles, dysplasia of clavicles, respiratory insufficiency, and an enlarged placenta with short umbilical cord. Histologic abnormalities of the skin include thin dermis with paucity and hypoplasia of the appendages and abnormally arranged collagen bundles. Elastic fibers are nearly missing. The subcutaneous fat is slightly increased. These skin findings usually appear after 22 or 24 weeks of gestation, which is why prenatal diagnosis with skin biopsy may fail. This disease is easily differentiated from other congenital FADS, such as Pena-Shokeir syndrome, COFS syndrome, Parana hard-skin syndrome, etc. We report on an affected boy of consanguineous parents and 30 previous cases are reviewed.
Subject(s)
Skin Diseases/congenital , Skin Diseases/genetics , Calcification, Physiologic , Chromosome Inversion , Chromosomes, Human, Pair 9 , Collagen/metabolism , Contracture/congenital , Contracture/genetics , Fatal Outcome , Female , Fetal Growth Retardation , Genes, Recessive , Humans , Infant, Newborn , Infant, Premature , Infant, Premature, Diseases , Karyotyping , Keratins/metabolism , Kyphosis/congenital , Kyphosis/genetics , Male , Natal Teeth , Pregnancy , Skin Diseases/pathology , SyndromeABSTRACT
The objective of this study was to describe the characteristic prenatal findings of a ductus arteriosus-dependent pulmonary circulation secondary to cardiac malformations. B-mode, color and pulsed wave Doppler echocardiography were performed in seven fetuses with severe pulmonary stenosis or atresia. All findings were confirmed postnatally by echocardiography and cardiac catheterization or autopsy. Severe fetal pulmonary stenosis or atresia was characterized by decreased pulmonary valve diameters, frequently with reduced pulmonary artery diameters, increased flow velocities or absent flow across the stenotic pulmonary valve, increased ascending aorta diameters, slightly increased aortic velocities and normal umbilical and middle cerebral artery Doppler wave forms. In all cases, prenatal assessment of neonatal ductus dependence was possible by demonstrating reverse flow across the fetal ductus with peak systolic velocities ranging from 0.9-2.0 m/s and absent diastolic flow. Ductal diameters were slightly decreased, ranging from 2-4 mm. Prenatal detection of a ductus-dependent pulmonary circulation is a strong indication of the presence of severe pulmonary stenosis or atresia. Its diagnosis allows avoidance of maternal administration of drugs with constrictive effects upon the ductus, interdisciplinary planning of perinatal management, early postnatal confirmation of the diagnosis, and early postnatal intervention, in particular administration of prostaglandins to prevent life-threatening ductal closure.
Subject(s)
Ductus Arteriosus/diagnostic imaging , Echocardiography, Doppler , Heart Defects, Congenital/diagnostic imaging , Pulmonary Atresia/diagnostic imaging , Pulmonary Circulation , Pulmonary Valve Stenosis/diagnostic imaging , Ultrasonography, Prenatal , Blood Flow Velocity , Female , Fetal Diseases/diagnostic imaging , Heart Defects, Congenital/physiopathology , Humans , Infant, Newborn , Pregnancy , Pulmonary Atresia/physiopathology , Pulmonary Valve Stenosis/physiopathologyABSTRACT
The following parameters were measured in 63 renal biopsy specimens, most of which exhibited mesangioproliferative glomerulonephritis: the relative area of the interstitium and the area of the capillaries in the cortex and outer stripe of the outer medulla, and the area of the epithelium of the proximal tubules and of the ascending limbs of Henle's loop. The percentage of hyalinized glomeruli was also determined. Investigation of correlations between these values and parameters of renal function revealed the following: 1) The serum creatinine concentration increases and the endogenous creatinine clearance decreases significantly as the interstitium of both the cortex and the outer stripe of the outer medulla increases in width. 2) The urine osmolality decreases significantly as the epithelial areas of the proximal tubules and ascending limbs of Henle's loop decrease, and as the serum creatinine concentration rises and the areas of the interstitium increase. 3) No significant correlation exists between the percentage of hyalinized glomeruli and the urine osmolality. 4) The total area of the intertubular capillaries in the cortex decreases significantly as the interstitium in this area increases in width and as the serum creatinine concentration increases. 5) Compensatory hypertrophy of individual nephrons, as proposed by Bricker's hypothesis, was found only where more than 90% of the glomeruli were hyalinized.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Glomerulonephritis, Membranoproliferative/pathology , Kidney Diseases/pathology , Kidney/pathology , Adult , Biopsy , Female , Glomerular Filtration Rate , Glomerulonephritis, Membranoproliferative/physiopathology , Humans , Kidney/physiopathology , Kidney Concentrating Ability/physiology , Kidney Diseases/physiopathology , Male , Osmolar ConcentrationABSTRACT
The following results were obtained in a long-term retrospective study including 250 patients with focal sclerosing glomerulonephritis: 1. The renal survival rate (RSR) was 90% at 5 years and 67% at 10 years, the average period of observation being 4.7 years. 2. Univariate analysis revealed that the following morphologic and clinical parameters are associated with an increased risk of terminal renal failure or death due to renal causes: a) Tubulointerstitial changes in the form of interstitial fibrosis, with or without acute renal failure; b) Advanced glomerular lesions; c) Advanced vascular alterations; d) Nephrotic syndrome present at the time of the biopsy; e) Elevated serum creatinine concentration at the time of the biopsy; f) Arterial hypertension at the time of the biopsy; g) Greater age at diagnosis; h) Male sex. 3. Multivariate survivorship analysis showed that tubulointerstitial changes and the presence of nephrotic syndrome at the time of biopsy are the only variables with significant independent predictive value for the outcome. Assessment of these factors thus allows the pathologist to make a relevant statement concerning the probable course and prognosis of the disease at the time of the diagnostic biopsy.
Subject(s)
Glomerulonephritis/physiopathology , Glomerulosclerosis, Focal Segmental/physiopathology , Kidney Cortex/physiopathology , Kidney Tubules/physiopathology , Adolescent , Adult , Age Factors , Analysis of Variance , Biopsy, Needle , Blood Pressure , Creatinine/blood , Female , Glomerular Filtration Rate , Glomerulosclerosis, Focal Segmental/complications , Glomerulosclerosis, Focal Segmental/drug therapy , Glomerulosclerosis, Focal Segmental/pathology , Humans , Kidney Cortex/pathology , Kidney Tubules/pathology , Male , Middle Aged , Nephrotic Syndrome/complications , Nephrotic Syndrome/physiopathology , Prognosis , Retrospective Studies , Sex FactorsABSTRACT
The morphometric investigation of the proximal and distal tubules, the cortical interstitium, the intertubular capillaries, the renal corpuscles and the juxtaglomerular apparatuses (JGAs) in 56 cases in the oligoanuric, polyuric, and normuric phases of human acute renal failure (ARF), 6 cases of myeloma kidney with clinically confirmed ARF and 21 control kidneys revealed the following: (1) The main pathological change in human ARF is swelling of the epithelial cells of the proximal and distal tubules. Necrosis of these cells was observed in some cases but usually only as single cell necroses. (2) The interstitium of the cortex and of the outer stripe of the outer medulla is significantly widened in most cases of ARF. (3) In proximal tubules proximal to occluding casts (which were observed only in the plasmacytoma cases), the lumina are not widened but are narrower than normal, and the cross-sectional area of the epithelium is not greater but smaller than normal. (4) The JGAs were significantly larger in kidneys in the oligoanuric phase of ARF (with 1 exception) than in normal kidneys. In the normuric and polyuric phases they were slightly (not significantly) smaller than normal. In myeloma kidneys with occluding casts and/or diffuse interstitial fibrosis, the JGAs were significantly smaller than normal. From these findings it is concluded that: (1) The fall in glomerular filtration rate (GFR) in the postshock phase of ARF is not caused by nonselective back-diffusion of the primary urine through necrotic tubules or by compression of the lumina of the proximal and distal tubules by interstitial edema. A fall in GFR associated with occluding casts in the distal tubules is found only in the myeloma kidney and does not lead to widening of the proximal tubules but to tubular atrophy and narrowing of the lumen. (2) The casts seen in the lumina of the ascending limb of Henle's loop in some cases of ARF, which consist of hemoglobin, Tamm-Horsfall protein or desquamated blebs, do not occlude the lumen, since they are not associated with atrophy or luminal dilatation of the proximal tubules. (3) The JGAs with their secretory product renin-angiotensin II, together with adenosine, which is released in kidneys with ischemic or toxic damage, play a critical role in the pathogenesis of ARF. (4) In myeloma kidneys with ARF, in which the JGAs are markedly atrophic, the potentiated effect of adenosine that has been observed with a chronic absence of urine flow probably leads to a progressive, irreversible drop in GFR associated with tubular atrophy.
Subject(s)
Acute Kidney Injury/etiology , Kidney/pathology , ADP-Ribosylation Factor 6 , Acute Kidney Injury/pathology , Adenosine/analysis , Adult , Biopsy , Epithelium/pathology , Female , Humans , Juxtaglomerular Apparatus/pathology , Kidney Tubules/pathology , Male , Renin-Angiotensin System/physiologyABSTRACT
This study is concerned with the correlation between tubulointerstitial changes (interstitial fibrosis, acute renal failure, and interstitial fibrosis with acute renal failure), glomerular changes (focal and segmental lesions, hyperperfusion lesions), vascular changes, clinical data at the time of biopsy (serum creatinine concentration, creatinine clearance, hematuria, proteinuria, and hypertension) and first symptoms (hematuria, proteinuria and hypertension) and the kidney survival rate in 239 patients with IgA nephritis without nephrotic syndrome. The morphological and clinical parameters were subjected to multivariate analysis in order to examine their significance with regard to the prognosis. The interstitial fibrosis was proven to be the most important morphological parameter, and the most important clinical parameters were the serum creatinine concentration and the creatinine clearance.
Subject(s)
Glomerulonephritis, IGA/pathology , Acute Kidney Injury/etiology , Acute Kidney Injury/pathology , Adult , Arterioles/pathology , Biopsy , Female , Glomerulonephritis, IGA/complications , Glomerulonephritis, IGA/diagnosis , Humans , Kidney/blood supply , Kidney Glomerulus/pathology , Kidney Tubules/pathology , Male , Prognosis , Time FactorsABSTRACT
This study reports the pathological-anatomical diagnoses in 180 cases in which a diagnosis of acute renal failure (ARF) had been made on clinical grounds. The clinical and pathological diagnoses were in agreement in 43.3% of the cases. In 56.7%, the pathological-anatomical diagnosis differed from the clinical diagnosis. Glomerulonephritis (GN) was particularly often concealed behind ARF, in particular rapidly progressive GN, but also acute interstitial nephritis or hemolyticuremic syndrome. In addition, the clinical diagnoses in cases with a pathological-anatomical diagnosis of ARF are presented. Finally, the clinical diagnoses made in cases with a pathological-anatomical diagnosis of GN with ARF are reported. It is thus shown that the pathologist is in a position to distinguish GN with true compensated retention from GN with transient ARF simulating compensated retention.