Pathogenesis of acardiac twinning: clues from an almost acardiac twin.

OBJECTIVE: To search for clues to the pathogenesis of acardiac twinning. METHODS: We examined a case of monoamniotic twins in which twin A's only sonographic abnormality was a dilated, tortuous ductus venosus. Twin B also had this abnormality as well as multiple other anomalies that included enormous hydrops and a severely hypoplastic heart. Following termination of pregnancy, autopsy was performed. RESULTS: Postmortem examination of the placenta confirmed monochorionic, monoamniotic placentation with two adjacent trivascular cords. Autopsy confirmed the sonographic findings of enormous hydrops in twin B with a severely malformed, almost nonexistent heart. In addition, the liver was small and was represented by a cyst-like structure with thin rims of congested parenchyma surrounding large vascular spaces. CONCLUSION: We believe the sequence of events in this case was early twin-to-twin transfusion resulting in a dysfunctional heart in twin B. This enabled a twin reversal arterial perfusion sequence with further deterioration of twin B's heart and extreme congestion of deoxygenated blood exiting the heart into the inferior vena cava and ductus venosus. This case supports the concept that circulatory reversal in the face of an initially functioning heart may lead to congestion, tissue hypoxia and secondary organ atrophy.

Lack of evidence for an association between neurofibromatosis type I and intracranial aneurysms: autopsy study and review of the literature.

BACKGROUND AND PURPOSE: Neurofibromatosis type I (NF1) is an autosomal dominant, hereditary, neurocutaneous syndrome purported to be associated with intracranial aneurysms. To study the relationship between NF1 and intracranial aneurysms, we have analyzed all intracranial autopsies of NF1 patients performed at our institution from 1889 to 1999 and analyzed all intracranial aneurysm cases at our institution from 1990 to 1999 in an attempt to identify patients with NF1. In addition, we have reviewed published clinical series of NF1 patients. METHODS: The autopsy database at our institution, which contains 50 000 cases from 1889 to 1999, was searched to identify NF1 patients, and the results of these autopsies were reviewed. The prevalence of intracranial aneurysms in these NF1 patients was compared with the prevalence of intracranial aneurysms in our hospital's autopsy population and with the published prevalence of intracranial aneurysms in the general population. To identify patients with intracranial aneurysms and NF1, our institution's intracranial aneurysm database was searched for patients with clinical manifestations of NF1. Published clinical series of NF1 patients were identified through searches of the literature. RESULTS: None of the 25 autopsy patients with NF1 had an intracranial aneurysm. None of the 925 patients treated for intracranial aneurysms were affected by NF1. A review of the literature identified 8 comprehensive clinical studies, all of which failed to document any relationship between NF1 and intracranial aneurysms. CONCLUSIONS: The autopsy prevalence of no NF1 patients with intracranial aneurysms out of 25 is not different from the prevalence of intracranial aneurysms in the general autopsy population. In addition, no patients treated for intracranial aneurysms at this institution had NF1. These findings are supported by the observation that an association between NF1 and intracranial aneurysms has never been identified in 8 large clinical studies of NF1 patients. We conclude that there is a lack of evidence for any association between NF1 and intracranial aneurysms.

Association between nonbacterial thrombotic endocarditis and hypoxigenic pulmonary diseases.

Observation of patients with nonbacterial thrombotic endocarditis (NBTE) in the setting of hypoxia from various lung diseases raised the question of a possible pathogenetic relationship between hypoxia and the development of NBTE. We reviewed 50 autopsied patients with NBTE and compared them with 50 age/race/gender-matched control patients without NBTE. We noted the lung weight and graded the histopathological severity of lung involvement by disease, clinical respiratory compromise, and the extent of any cancer present. Patients with NBTE had heavier lungs (P < 0.01) and histologically and clinically more severe pulmonary disease (both P < 0.005). There was no statistically significant difference in the extent of metastatic cancer between the NBTE patients and the controls (P > 0.5). When patients with cancer were excluded from the group of NBTE cases, there was still a statistically significant preponderance in the mean lung injury and clinical compromise scores of the NBTE patients (both P < 0.05), but the difference in lung weight was no longer statistically significant (P > 0.05). The study suggests that, in some patients, hypoxia may lead to NBTE, possibly through altered coagulation states.

Von Willebrand factor-cleaving protease activity and proteolysis of von Willebrand factor in bone marrow transplant-associated thrombotic microangiopathy.

INTRODUCTION: Thrombotic microangiopathy (TM) of the fulminant type occurring in patients following bone marrow transplant (BMT) has clinical manifestations that are similar to thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome, but the outcome is generally fatal despite conventional therapy. Idiopathic acquired TTP has been associated with IgG inhibitors to the cleaving protease of von Willebrand factor (vWF) in plasma. In this study, we investigated the role of the vWF protease and vWF proteolysis in the pathogenesis of BMT-associated TM of the fulminant type. METHODS: vWF antigen level, vWF multimeric pattern, and vWF metalloprotease activity were investigated in the plasma samples of six consecutive patients with acute BMT-associated TM. Histologic and immunohistochemical studies were also performed on autopsy kidney specimens from four of the patients. All six patients had the fulminant type of the disorder with a fatal outcome and none of the patients responded to plasma infusion. RESULTS: The vWF-cleaving protease activity in plasma was normal in all patients. However, analysis of the vWF multimeric pattern showed a decrease of high molecular weight multimers. The decrease of large multimers may be caused by vWF-platelet binding as well as shear enhanced proteolysis of vWF. In the four patients who had an autopsy, a pattern of arteriolar thrombosis, distinct from that of TTP, was detected in the kidneys. CONCLUSION: These findings suggest that BMT-associated TM of the fulminant type is a heterogeneous process and distinct from TTP in pathogenesis. Analysis of vWF protease and vWF multimeric distribution are valuable tools in making the distinction between BMT-associated TM and TTP.

Patterns of congenital lower urinary tract obstructive uropathy: relation to abnormal prostate and bladder development and the prune belly syndrome.

The pathogenesis of lower urinary tract obstruction is disputed, particularly its relation to both abnormal prostatic development and the prune belly syndrome (PBS). In an attempt to clarify this issue we examined 11 males (17-38 weeks gestation) with PBS who were autopsied at our institution. The lower urinary tract was embedded intact and prepared as serial histologic sections. Of the 11 cases, 8 demonstrated mechanical obstruction of the lower urinary tract. In five of these eight cases, a "flap-valve" structure was formed by an abnormal angulation between the prostatic and penile portions of the urethra. These had dilated, thin-walled bladders and prostates and moderate to severe renal dysplasia. One of the eight cases had a valve-like obstruction at the level of the mid-prostatic urethra associated with a complex cloacal malformation and a thin-walled bladder, another case had an epithelial plug at the penile meatus, and the last of the eight cases had a posterior urethral valve. The three remaining cases showed no mechanical obstruction. However, each had megacystis with marked thickening, interstitial fibrosis, and disarray of smooth muscle bundles in the bladder wall. In 10 cases, the prostate had no or only sparse, flattened glands. These results suggest that the abnormal development of the prostate in PBS may be explained as a pressure-induced dysplasia rather than a primary maldevelopment. The findings further suggest that abnormal prostatic development and the prune belly syndrome may arise from either anatomic obstruction of various types or functional obstruction from megacystis.

Echocardiographic findings in fulminant and acute myocarditis.

OBJECTIVES: We sought to use echocardiography to assess the presentation and potential for recovery of left ventricular (LV) function of patients with fulminant myocarditis compared with those with acute myocarditis. BACKGROUND: The clinical course of patients with myocarditis remains poorly defined. We have previously proposed a classification that provides prognostic information in myocarditis patients. Fulminant myocarditis causes a distinct onset of illness and severe hemodynamic compromise, whereas acute myocarditis has an indistinct presentation, less severe hemodynamic compromise and a greater likelihood of progression to dilated cardiomyopathy. METHODS: Echocardiography was performed at presentation and at six months to test the hypothesis that fulminant (n = 11) or acute (n = 43) myocarditis could be distinguished morphologically. RESULTS: Patients with both fulminant (fractional shortening 19 +/- 4%) and acute myocarditis (17 +/- 7%) had LV systolic dysfunction. Patients with fulminant myocarditis had near normal LV diastolic dimensions (5.3 +/- 0.9 cm) but increased septal thickness (1.2 +/- 0.2 cm) at presentation, while those with acute myocarditis had increased diastolic dimensions (6.1 +/- 0.8 cm, p < 0.01 vs. fulminant) but normal septal thickness (1.0 +/- 0.1 cm, p = 0.01 vs. fulminant). At six months, patients with fulminant myocarditis had dramatic improvement in fractional shortening (30 +/- 8%) compared with no improvement in patients with acute myocarditis (19 +/- 7%, p < 0.01 for interaction between time and type of myocarditis). CONCLUSIONS: Fulminant myocarditis is distinguishable from acute myocarditis by echocardiography. Patients with fulminant myocarditis exhibit a substantial improvement in ventricular function at six months compared with those with acute myocarditis. Echocardiography has value in classifying patients with myocarditis and may provide prognostic information.

Long-term outcome of fulminant myocarditis as compared with acute (nonfulminant) myocarditis.

BACKGROUND: Lymphocytic myocarditis causes left ventricular dysfunction that may be persistent or reversible. There are no clinical criteria that predict which patients will recover ventricular function and which cases will progress to dilated cardiomyopathy. We hypothesized that patients with fulminant myocarditis may have a better long-term prognosis than those with acute (nonfulminant) myocarditis. METHODS: We identified 147 patients considered to have myocarditis according to the findings on endomyocardial biopsy and the Dallas histopathological criteria. Fulminant myocarditis was diagnosed on the basis of clinical features at presentation, including the presence of severe hemodynamic compromise, rapid onset of symptoms, and fever. Patients with acute myocarditis did not have these features. The incidence of the end point of this study, death or heart transplantation, was ascertained by contact with the patient or the patient's family or by a search of the National Death Index. The average period of follow-up was 5.6 years. RESULTS: A total of 15 patients met the criteria for fulminant myocarditis, and 132 met the criteria for acute myocarditis. Among the patients with fulminant myocarditis, 93 percent were alive without having received a heart transplant 11 years after biopsy (95 percent confidence interval, 59 to 99 percent), as compared with only 45 percent of those with acute myocarditis (95 percent confidence interval, 30 to 58 percent; P=0.05 by the log-rank test). Fulminant myocarditis was an independent predictor of survival after adjustments were made for age, histopathological findings, and hemodynamic variables. The rate of transplantation-free survival did not differ significantly between the patients considered to have borderline myocarditis and those considered to have active myocarditis according to the Dallas histopathological criteria. CONCLUSIONS: Fulminant myocarditis is a distinct clinical entity with an excellent long-term prognosis. Aggressive hemodynamic support is warranted for patients with this condition.

Septation and differentiation of the embryonic human cloaca.

BACKGROUND/PURPOSE: Limitations in methodologies have fostered controversy regarding the septation of the human embryonic cloaca. The aim of this study was to evaluate the septation of the human embryonic cloaca. METHODS: Using the Carnegie Embryological Collection and specimens at Johns Hopkins, Baltimore, MD, the authors studied 12 embryos and five fetuses. Embryo photomicrographs were reconstructed using three-dimensional modeling. RESULTS: In Carnegie stage 13 the authors observed a cloaca, distinct primitive urogenital sinus, and anorectum separated by the urorectal septum. The primitive urogenital sinus and anorectum enter the cloaca separated from the amniotic space by the cloacal membrane. As the embryo becomes a fetus it lengthens, grows, expands and rotates through a process called transformation. Transformation gives rise to a loss of caudal curvature and a decrease in distance between the septum and membrane, but these structures do not fuse. Disintegration of the cloacal membrane produces openings for the urogenital sinus and anorectum. CONCLUSIONS: The observations suggest that the urogenital sinus and anorectum form early and are separated by the urorectal septum as a passive structure. There does not appear to be septation or differentiation of the cloaca itself.

Altered smooth muscle development and innervation in the lower genitourinary and gastrointestinal tract of the male human fetus with myelomeningocele.

PURPOSE: We determine whether smooth and skeletal muscle or nerve density is altered in the lower genitourinary or gastrointestinal tract of male human fetuses with myelomeningocele at 20 weeks of gestation. MATERIALS AND METHODS: We serially cross sectioned the lower genitourinary and gastrointestinal tracts in 7 male fetuses (mean age 20 weeks of gestation) with myelomeningocele and 4 age matched controls. Immunohistochemical staining was performed using Masson's trichrome stain and antibodies to smooth and skeletal muscle actin. S-100 protein staining for Schwann cell localization and neurofilament protein was also done. Fluorescein and rhodamine double immunolabeling was used to demonstrate the co-expression of smooth and skeletal muscle. RESULTS: Peripheral neural innervation of the bladder, prostate and rectum was markedly decreased in myelomeningocele. Masson's trichrome and smooth muscle actin staining also demonstrated that smooth muscle was less well differentiated in myelomeningocele specimens. Scant smooth muscle was present in the myelomeningocele bladder and bladder neck with an excess of collagen in an interfascicular and intrafascicular distribution. Double immunofluorescence staining revealed persistent co-expression of smooth and skeletal muscle actin by myocytes in the myelomeningocele detrusor, while in the control bladder there was only smooth muscle expression. The skeletal muscle component of structures in fetuses with myelomeningocele, including the external sphincter, was similar to that in controls. Prostatic size, ductal morphogenesis and smooth muscle were decreased compared to those in controls. CONCLUSIONS: A global defect exists in the development of smooth muscle in myelomeningocele in the lower genitourinary and gastrointestinal tracts by 20 weeks of gestation. Peripheral nerve density is decreased in smooth muscle in myelomeningocele, suggesting that an intact nervous system is important for the development of normal smooth muscle. Fetal surgery with coverage of the spinal cord in select cases may prevent progressive environmental injury to the somatic nervous system during the second half of gestation. However, achieving normal autonomic function is unlikely due to the extent of early global organ maldevelopment.

Surfactant treatment may accelerate epithelial cell regeneration in hyaline membrane disease of the newborn.

Previous studies of histologic changes in the lungs of infants with hyaline membrane (HMD) disease of the newborn treated with surfactant have focused on the occurrence of hemorrhage and bronchopulmonary dysplasia (BPD). Observations in autopsied infants with HMD suggested a possible acceleration of epithelial cell regeneration in those receiving surfactant. We studied lungs of the 11 autopsied infants with HMD treated with surfactant, who survived less than 1 week, and compared them to 22 infants with HMD not given surfactant. Epithelial cell regeneration, BPD, and airway and interstitial hemorrhage were graded on a 0-to-3 scale. Treated infants showed significantly more epithelial cell regeneration (p<0.05) and airway hemorrhage (p<0.05). Also, treated infants showed recognizable epithelial regeneration 1 day earlier than the nontreated group. The study supports the observation that regeneration of the necrotic respiratory epithelium of HMD is accelerated in infants treated with surfactant.

Polyarteritis nodosa of the pericardium: antemortem diagnosis in a pericardiectomy specimen.

A 74-year-old white woman with diffuse myalgias, low grade fever, and pericardial effusion was found to have polyarteritis nodosa (PAN) in a pericardiectomy specimen. This diagnosis was confirmed at autopsy. Although pericardial involvement in PAN has been described, this is the first report of PAN diagnosed in a pericardiectomy specimen.

The autopsy: still important in cardiac surgery.

BACKGROUND: This study examined the ability of autopsy to confirm or dispute presumptive cause of death among cardiac surgery patients. METHODS: Autopsy reports were compared with mortality conference notes that were dictated prospectively before autopsy results were available. Between January 1985 and December 1995, there were 600 hospital deaths among 13,029 adult cardiac surgery patients (4.6% mortality). Of these 600 deaths, 147 (24.5%) had postmortem examination. RESULTS: Annual autopsy rate remained constant over the course of the study. Autopsied patients were younger (60.4 +/- 15 versus 66.7 +/- 13 years [mean +/- standard error of the mean]; p < 0.0001), but their race and sex distributions were similar to deceased patients not having autopsy. Autopsy confirmed clinical presumptive cause of death in 52% (76), disputed clinical diagnosis in 9.5% (14), provided definitive diagnosis in the absence of clinical diagnosis in 13.6% (20), and failed to provide definitive diagnosis in 25% (37). One third of autopsies (39%; 57) provided information that was clinically unrecognized and might have altered therapy and outcome if known premortem. As determined by autopsy, common causes of death were cardiac (27%; 39), unknown (25%; 37), sepsis (14%; 21), stroke (8.8%; 13), cholesterol embolism (4.1%; 6), pulmonary embolism (4.1%; 6), and adult respiratory distress syndrome (4.1%; 6). CONCLUSIONS: Autopsy reveals or confirms cause of death in nearly three quarters of cardiac surgical deaths and provides information that differs significantly from premortem clinical impression more than 20% of the time. As such, the autopsy remains important to quality assurance in cardiac surgical care.

The spinal cord lesion in human fetuses with myelomeningocele: implications for fetal surgery.

Recently produced experimental evidence suggests that secondary traumatic injury and degenerative changes, acquired in utero, to the openly exposed neural tissue may be primarily responsible for the massive neurological deficit associated with myelomeningocele (MMC). The goal of this study was to examine the morphology of human fetuses with MMC to determine if acquired trauma to the spinal cord could be identified. The MMC lesions with surrounding tissues from 10 human fetuses ranging in gestational age between 19 and 23 weeks were prepared with serial histological sections. The MMC lesions were characterized by an open vertebral arch, an open dura mater fused laterally to the dermis, and an open pia mater fused laterally to the epidermis. The spinal cord was exposed, without any meningeal, bony, or cutaneous covering, and was resting on the dorsal aspect of the abnormal arachnoid sac created by the fusion of the meninges to the cutaneous tissues. The exposed neural tissue had undergone varying degrees of recent traumatic injury as a result of its exposed position, ranging from nearly complete preservation of neural elements in four cases to nearly complete loss in two cases. The neural tissue remaining in the MMC with partial loss contained hemorrhages and abrasions from recent injury, suggesting that injury occurred during passage through the birth canal. The presence of dorsal and ventral parts of the cord with nerve roots and ganglia demonstrated that these structures had formed during development and that the loss of tissue by injury was a secondary change. The results support the concept that performing in utero surgery could protect the exposed but initially well-developed and uninjured cord, prevent secondary neural injury, and preserve neural function in the human fetus with myelomeningocele.

Accumulation of glycosphingolipids in human atherosclerotic plaque and unaffected aorta tissues.

We have measured the levels of glycosphingolipids and the activity of glycosphingolipid glycosyltransferases in human aortic intima and media from patients who died of atherosclerosis. The effects of lactosylceramide (LacCer) and glucosylceramide (GlcCer) from plaque intima on smooth muscle cell proliferation were assessed. When the GlcCer data was expressed as (micrograms GlcCer/mg cholesterol and/mg total phospholipid, a 28-fold and 7-fold increase in plaque intima compared to normal intima was observed. Similarly, the level of LacCer was elevated 5-fold and 4-fold, respectively, compared to unaffected intima. The activity of UDP-GlcCer: ceramide beta 1-->4 glucosyltransferase (GlcT-1) was similar in unaffected tissue, fatty streaks, and plaques. However, the activity of UDP-galactose: GlcCer, beta 1-->4 galactosyltransferase (GalT-2) activity was moderately higher in plaque than in unaffected tissue. LacCer, but not GlcCer derived from plaque intima exerted a approximately 2.8-fold increase in the proliferation of human aortic smooth muscle cells grown in tissue culture compared to control presumably due to a marked increase in LacCer molecular species containing C16:0, C22:1, and C24:0 fatty acids in plaque intima compared to control. In sum, our findings provide an interesting and novel pathogenic mechanism of lactosylceramide mediated plaque formation via stimulation of aortic smooth muscle cell proliferation.

Intravascular magnetic resonance imaging of aortic atherosclerotic plaque composition.

Magnetic resonance imaging (MRI) may be an excellent tool to define atherosclerotic plaque composition, but surface MRI (SMRI) suffers from a low signal-to-noise ratio and low resolution of arterial images. Intravascular MRI (IVMRI) represents a potential solution for acquiring high-quality in vivo images of atherosclerotic plaques. Isolated segments of 11 thoracic human aortas obtained at autopsy were imaged by IVMRI using an intravascular receiver catheter coil designed and built at our institution. Images obtained by IVMRI were compared with corresponding images obtained by SMRI and with histopathological aortic cross sections. The intensity of intimal thickness and plaque components was graded by IVMRI and histopathology using a score of 1 for mild, 2 for moderate, and 3 for severe intensity. IVMRI had an agreement of 75% with histopathology in fibrous cap grading (37.5% expected, kappa = 0.60, P < 0.001) and of 74% in necrotic core grading (39% expected, kappa = 0.57, P < 0.001). Intraplaque calcification was correctly graded by IVMRI in six of the eight plaques in which histopathology recognized calcium. The analysis of intimal thickness showed 80% agreement between IVMRI and histopathology (52% expected, kappa = 0.59, P < 0.001). IVMRI image features were similar to those of SMRI. In addition, IVMRI accurately determined atherosclerotic plaque size in comparison with histopathology and SMRI (slope = 1.25 cm2, r = 0.99, P < 0.001 for luminal area by IVMRI vs histopathology; slope = 0.97 cm2, r = 0.996, P < 0.001 for luminal area by IVMRI vs SMRI). IVMRI has the potential to provide important prognostic information in patients with atherosclerosis because of its ability to accurately assess both plaque composition and size.

Primary cardiac tumors causing sudden death: a review of the literature.

Sudden unexpected death accounts for 200,000-400,000 deaths each year in the United States. Although the vast majority of these fatalities are related to atherosclerotic heart disease, a small percentage (approximately 0.0025%) stem from primary cardiac neoplasms. There have been 120 cases of sudden death attributed to primary cardiac tumors in the (published) literature. Although 103 of these lesions were histologically benign (86%), their intracardiac locations precipitated conductive and hemodynamic abnormalities that resulted in sudden death. These tumors are usually easily recognized at necropsy. The most common intracardiac lesion causing sudden death, endodermal heterotopia of the atrioventricular (AV) node, however, may not be discovered unless the AV node is microscopically examined. Owing to the rarity of these neoplasms, a brief review of their salient gross and microscopic features is in order.

One-month histologic response of transmyocardial laser channels with molecular intervention.

BACKGROUND: Transmyocardial revascularization reduces the symptoms and morbidity of patients with endstage ischemic heart disease. The mechanism is postulated to be the formation of transmural left ventricular channels through which oxygenated blood directly perfuses the myocardium. New techniques for molecular enhancement of angiogenesis and endothelial cell motility may represent strategies to augment this clinical benefit. METHODS: Triads of transmyocardial revascularization channels were placed in eight separate nonischemic sites on the hearts of 7 pigs weighing 68 to 78 kg, which were allowed to recover and were then sacrificed at 28 days. In addition, one triad pair was injected with vascular endothelial growth factor, and two triad pairs received an adenovirus vector with or without the gene encoding for human profilin, which increases endothelial cell motility and adhesion. The remaining triad pair stood untreated (laser only). The histologic changes were graded (0 through 3) by an independent pathologist without knowledge of the treatment modality. Profilin production and vascular endothelial growth factor activation using a tyrosine kinase assay were monitored. RESULTS: Transmyocardial revascularization alone resulted in a significant injury response (p < 0.01), including increased vascularity without patent channels. Vascular endothelial growth factor increased surrounding inflammation (p < 0.01) without improving vascularity or patency. Profilin content in tissues was increased but nonspecifically because inflammation resulting from adenovirus also induces higher profilin concentrations. CONCLUSIONS: The clinical benefit of transmyocardial revascularization may result simply from a nonspecific histologic response to injury. Molecular interventions appear to stimulate more inflammation but no additional angiogenesis. Further improvement in the clinical benefit of transmyocardial revascularization awaits the successful stimulation of a true angiogenic response.

Acquired spinal cord injury in human fetuses with myelomeningocele.

Experimental studies have shown that there is a potential to attempt in utero repair of myelomeningocele in human fetuses. To provide a better understanding of the pathology of these lesions we prospectively studied eight stillborn human fetuses with myelomeningocele autopsied at The Johns Hopkins Hospital. The intact vertebral column with surrounding structures was removed, processed as a single block, and prepared as serial histologic sections. Study of the slides showed in all cases that in the center of the myelomeningocele the vertebral arch was open, the arrangement of meninges was such that the dura mater was open and in continuity with the deep layers of the dermis, and the pia mater was open and in continuity with a layer consisting of the superficial dermis and the epidermis. These meningeal relationships created an abnormally configured arachnoid space containing cerebrospinal fluid ventral to the spinal cord, which rested on the open pia mater and was exposed on the dorsal aspect of the sac. At the level of the myelomeningocele the naked cord had undergone varying degrees of injury up to complete loss of neural tissue. Where ventral remnants of the cord remained it was evident that a large degree of normal development of the cord had occurred. In most instances it appeared that the injury or destruction of the dorsal spinal cord was recent and consistent with occurrence during delivery. The results of this study support the concept that in utero surgery could preserve and protect the exposed spinal cord in a myelomeningocele of a human fetus and thus could reduce the severity of the neurologic deficit at birth.

The WAF1-mediated p53 growth-suppressor pathway is intact in the coronary arteries of heart transplant recipients.

It has been suggested that the interaction of cytomegalovirus (CMV) with the p53 tumor suppressor gene product plays a role in the development of coronary artery restenosis after angioplasty. CMV nucleic acids have been observed in the coronary arteries of allografted hearts, suggesting a possible role for the interaction of CMV with p53 in the development of accelerated graft arteriosclerosis in transplant recipients. Formalin-fixed, paraffin-embedded sections of coronary arteries from 19 transplanted hearts were immunostained for the p53 gene product using Target Unmasking Fluid (TUF)-mediated immunohistochemistry and the anti-p53 antibodies CM1 and DO7. Fresh-frozen sections of coronary arteries were also available from six of the 19 hearts, and these fresh-frozen sections were immunostained for the p53 gene product with the DO7 antibody and for WAF1 using the anti-WAF1 antibody EA10. Focal and weak staining for p53 was observed in smooth muscle and endothelial cells in two of 19 vessels, whereas the remaining 17 did not stain. CMV nucleic acids were previously shown in six of 13 of these hearts by in situ hybridization. The fresh-frozen sections of coronary arteries also did not stain for p53, but the smooth muscle cells in these vessels did stain intensely for WAF1. These results suggest three possibilities: (1) CMV-p53 interactions are not important in the development of accelerated graft arteriosclerosis; or (2) there is an interaction, but it is transient and not detectable at the time points examined in this study; or (3) there is an interaction, but binding of CMV to p53 leads to accelerated degradation of p53, as occurs with HPV-E6. The expression of WAF1 further suggests that the WAF1-mediated antiproliferative signal is intact in these vessels.