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D C Miller

Publications and source records attributed to D C Miller.

At least 181 records · Page 10Linked to original sources
PubMed1994

Diagnostic use of immunohistochemistry in neuropathology.

Immunohistochemistry has revolutionized both the research and diagnostic endeavors of anatomic and surgical pathologists, including neuropathologists. These methods, which use the high specificity of antibody recognition of target antigens, have largely replaced the more capricious, less sensitive, and less specific panoply of metallic impregnations and other histochemical methods that once were characteristics of neuropathology. With immunostaining, specific infectious agents, from ordinary bacteria to spirochetes, fungi, parasites, and especially viruses, can be identified as the causative agents of central nervous system diseases. Understanding of the pathogenesis and establishment of correct diagnoses of neurodegenerative disorders are both improved, and more precise and reliable diagnosis of central nervous system tumors has become a matter of immunophenotypic characterization using panels of relevant antibodies to supplement the recognition of standard histologic patterns. Newer trends in neuropathologic immunohistochemistry point to a better understanding of the molecular pathology of degenerative disorders and of tumors as specifically mutated oncogenetic or neurotoxic antigens are localized and identified in diseased brain and spinal cord tissues.

Brain↗
PubMed1993

Intravascular lymphomatosis. A systemic disease with neurologic manifestations.

BACKGROUND: Intravascular lymphomatosis (IL) is a systemic neoplasm that often involves the nervous system, inducing progressive neurologic deficits in the setting of undiagnosed or quiescent extranodal non-Hodgkin lymphoma. METHODS: The clinical and pathologic files of the Massachusetts General Hospital and New York University Medical Center and the English language literature were reviewed to identify all reports of intravascular lymphomatosis (angioendotheliomatosis) or other examples of a diffuse proliferation of neoplastic cells filling capillaries, arterioles, and venules. RESULTS: The authors report seven patients with IL and note 114 patients reported in the literature. Almost two-thirds (63%) of patients had neurologic manifestations, without abnormalities on bone marrow biopsy, chest and abdominal tomographic examinations for adenopathy, and cerebrospinal fluid (CSF) analysis. All patients had one or more of four syndromes, each reflecting a vascular occlusive process: progressive, multifocal cerebrovascular events; paraparesis, pain, and incontinence; a subacute encephalopathy; and peripheral or cranial neuropathies. CONCLUSIONS: The unexplained presence of any one or more of these neurologic syndromes should alert the physician to the possible presence of this disease.

Female↗
PubMed1993

Intravascular stenting of acute experimental type B dissections.

To evaluate the efficacy of intravascular stenting for acute aortic dissection, 12 dogs underwent surgical creation of an acute type B dissection. Intravascular ultrasound evaluated luminal diameter, distal propagation, and branch involvement. Three animals underwent no further treatment (control). In 9 dogs, balloon-expandable intravascular stents (15-20 mm) were placed proximally to compress the intimal flap. One dog with a small dissection had complete obliteration of the false lumen after initial stent placement. Six dogs with extension below the diaphragm were initially stented proximally to restore flow; 3 were left with a residual distal false lumen, while 3 had additional stents placed to obliterate their entire false lumen. In the final 2 dogs, proximal stenting resulted only in partial compression of the false lumen. Two animals died within 24 hr due to prolonged hemodynamic instability and aortic rupture at the intimal flap, respectively. Six weeks later, radiologic and histologic evaluation was performed on the 10 surviving animals. All stented true lumens were patent without thrombus formation, and stents were covered by neointima. In dogs with stenting of the entire dissection, the aortic wall had healed and no false lumen was present. However, in all dogs with only proximal obliteration, 1/2 with partial compression, and 2/3 controls, a patent false channel was present indicative of a chronic dissection. Thus, we found that intravascular stents can restore true lumen flow and obliterate the false lumen in experimental dissections; however, stenting limited to the proximal dissection does not prevent formation of a chronic residual patent false lumen.

Acute Disease↗
PubMed1993

Right ventricular dynamics during left ventricular assistance in closed-chest dogs.

To determine the effects of left ventricular assist device (LVAD) support on global right ventricular (RV) systolic mechanics, 8 closed-chest, conscious, sedated dogs were studied after placement of an LVAD (left ventricle to femoral artery bypass) and implantation of 27 tantalum markers into the left ventricular and RV walls for computation of biventricular volumes and geometry. Biplane cinefluoroscopic marker images and hemodynamic parameters were recorded during transient vena caval occlusion at various levels of LVAD support. Right ventricular contractility was assessed using end-systolic elastance and preload recruitable stroke work, and the myocardial (pump) efficiency of converting mechanical energy to external work (stroke work/total pressure-volume area) was calculated. With full LVAD support, RV end-diastolic volume increased from 60 +/- 15 to 62 +/- 17 mL (p < 0.002), pulmonary artery input impedance decreased from 940 +/- 636 to 587 +/- 347 dyne.s/cm5 (p < 0.007), and measurement of RV and left ventricular septal-free wall dimensions demonstrated a significant leftward septal shift (p < 0.0005). Global RV end-systolic elastance and preload recruitable stroke work decreased from 2.4 +/- 1.0 to 1.7 +/- 0.7 mm Hg/mL (p < 0.004) and 14.1 +/- 3.3 to 12.1 +/- 3.9 mm Hg (p < 0.02), respectively; however, RV power output and myocardial efficiency did not change significantly (p > 0.74 and p > 0.33, respectively). Therefore, during LVAD support, global RV contractility is impaired with leftward septal shifting, but RV myocardial efficiency and power output are maintained through a decrease in RV afterload and an increase in RV preload.

Animals↗
PubMed1993

Abnormal postoperative interventricular motion: new intraoperative transesophageal echocardiographic evidence supports a novel hypothesis.

Abnormal interventricular septal motion is a frequent finding after cardiac surgery. However, the time course and underlying mechanisms are not well understood. Nineteen patients, mean age 54 years (range 20 to 82 years), were studied with intraoperative transesophageal echocardiography at five specific times: with the chest closed (baseline), with the chest open and the pericardium closed, with both chest and pericardium open, after cardiopulmonary bypass with the chest open, and after cardiopulmonary bypass with the chest closed. In each patient interventricular septal motion was recorded from the transgastric view; tricuspid annular motion and Doppler color flow mapping of tricuspid regurgitation were obtained from the four-chamber view. All the echocardiographic data were stored on videotape and were later viewed in random sequence by one investigator who was aware of the baseline stage but was blinded to the other stages. All patients had normal septal motion before cardiopulmonary bypass. After cardiopulmonary bypass, with the chest still open, 5 of 17 patients (29%) with adequate recordings had abnormal septal motion while 13 of 17 patients (76%) with adequate recordings had abnormal tricuspid annular motion. After chest closure, only three patients (14%) had normal septal motion and one patient (6%) had normal tricuspid annular motion. Significant tricuspid regurgitation was an infrequent finding in all cases. It is concluded that abnormal interventricular septal motion occurs after cardiopulmonary bypass and is related to abnormal tricuspid annular motion. We hypothesize that suboptimal right ventricular myocardial preservation impairs the motion pattern of the right ventricle, including the tricuspid annulus.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Mutation screening of complete fibrillin-1 coding sequence: report of five new mutations, including two in 8-cysteine domains.

Marfan syndrome (MFS) is an autosomal dominantly inherited connective tissue disorder characterized by cardiovascular, ocular and skeletal manifestations. Previously, mutations in the fibrillin-1 gene on chromosome 15 (FBN1) have been reported to cause MFS. We have now screened 44 probands with MFS or related phenotypes for alterations in the entire fibrillin coding sequence (9.3 kb) by single strand conformation analysis. We report four unique mutations in the fibrillin gene of unrelated MFS patients. One is a 17 bp deletion and three are missense mutations, two of which involve 8-cysteine motifs. Another missense mutation was found in two unrelated individuals with annuloaortic ectasia but was also present in unaffected relatives and controls from various ethnic backgrounds. By using allele-specific oligonucleotide hybridization, we screened 65 unrelated MFS patients, 29 patients with related phenotypes and 84 control individuals for these mutations as well as for a previously reported mutation and two polymorphisms. Our results suggest that most MFS families carry unique mutations and that the fibrillin genotype is not the sole determinant of the connective tissue phenotype.

Adolescent↗
PubMed1993

Demyelinating disease versus tumor in surgical neuropathology. Clues to a correct pathological diagnosis.

Clinical presentations as well as radiological and histopathological findings in biopsies from patients with multiple sclerosis (MS) or other demyelinating disorders of the central nervous system are sometimes misleading, resulting in an erroneous diagnosis of brain or spinal cord tumor. We report 17 patients who presented with symptoms mimicking those of brain (14 cases) or spinal cord (three cases) tumors. Computerized tomography or magnetic resonance imaging studies or both were interpreted as consistent with a tumor in each case. All patients underwent surgery, and all 17 pathological specimens were eventually diagnosed as showing demyelinating disease, usually consistent with MS. In each case we examined a variety of histological features and immunohistochemical studies and addressed their relative importance in considering the diagnosis of MS. All cases showed perivascular lymphocytic inflammation with variable amounts of macrophage infiltration, necrosis, and edema. The hypercellularity of the lesions and the presence of atypical reactive astrocytes with mitotic figures were the disturbing features that might have led to the erroneous diagnosis of an astrocytic neoplasm. Immunohistochemistry for astrocytic (glial fibrillary acidic protein) and macrophage (HAM-56) markers are helpful in evaluating biopsies. Our results emphasize the need to perform special stains (i.e., for myelin and axons) that demonstrate myelin loss and relative preservation of axons and allow a correct diagnosis.

Adolescent↗
PubMed1993

A correlative study of p53 protein alteration and p53 gene mutation in glioblastoma multiforme.

The p53 tumor suppressor gene is frequently mutated in glioblastomas. Mutations within the p53 gene often result in aberrant expression of the p53 protein leading to protein accumulation within the nucleus of the cells which can be detected by immunochemistry. Many studies have correlated alterations of p53 protein expression with p53 gene mutations. Positive staining of tumor cells for p53 protein has been widely assumed, perhaps incorrectly, to signify the presence of p53 gene mutations. This study compared the immunostaining patterns for p53 protein in 37 glioblastomas with the molecular genetic data obtained by the single strand conformation polymorphism assay. p53 gene mutations were detected in 46% (17 of 37) of glioblastomas, while 65% (24 of 37) of glioblastomas were positive for protein accumulation by immunohistochemistry. Although 30 of 37 glioblastomas analyzed showed concordance for p53 protein expression and p53 gene mutations, a subset of seven glioblastomas showed discordant accumulation of the p53 protein in the absence of any detectable p53 gene mutations. The mdm-2 gene was assessed in 17 glioblastomas for gene rearrangements or amplification, but none were found. This result suggests that a mechanism other than p53 gene mutation can result in altered p53 protein expression.

Antibodies, Monoclonal↗
PubMed1993

Central nervous system gangliogliomas. Part 1: Pathology.

Histopathological features that suggest the diagnosis of ganglioglioma require, in most cases, confirmation by special stains to distinguish these tumors from other gliomas. For this purpose, immunostaining for synaptophysin, which has previously been shown to selectively label the cell surface of neoplastic ganglion cells, was used to retrospectively examine glioma tumor specimens. Sixty-three cases of ganglioglioma were identified. The files of the Division of Neuropathology of New York University Medical Center contained 45 tumors that had been diagnosed as ganglioglioma, of which 42 were verified by synaptophysin; three cases were reclassified, two as astrocytomas and one as a gangliocytic paraganglioma. Thus, a tumor identified as ganglioglioma based on other criteria was likely to be a ganglioglioma. The other 21 cases of gangliogliomas were originally diagnosed as astrocytoma or mixed glioma, but were shown by synaptophysin staining to be gangliogliomas. In some cases the ultimate diagnosis was obtained after radical surgery provided relatively abundant amounts of tissue, thereby limiting sampling errors, in contrast to the biopsies from which the original diagnoses were made. Histopathological review of these cases demonstrated that four features represent important clues to the correct diagnosis: 1) clusters of large cells potentially representing neurons (without such cells the tumor cannot be classified as a ganglioglioma); 2) no perineuronal clustering of the glial cells around the alleged neoplastic neurons; 3) fibrosis (desmoplasia); and 4) calcification. Binucleate neurons, previously suggested to be common in gangliogliomas, were not frequently found in this series, and lymphocytic infiltrates, while common, are so often found in other tumors that they gave no specific hint that any single neoplasm was a ganglioglioma. The glial elements were astrocytic in all cases, except that one tumor also had oligodendroglial and ependymal patterns. Four tumors also had small mature neurons, as seen in neurocytomas. Cells from one tumor were successfully grown in short-term tissue culture; the culture contained large dividing neurons with synaptophysin immunoreactivity as well as smaller dividing cells, demonstrating that the neuronal cells are a proliferating element in gangliogliomas.

Adult↗
PubMed1993

Central nervous system gangliogliomas. Part 2: Clinical outcome.

The records of 58 patients with gangliogliomas surgically treated between January 1, 1980, and June 30, 1990, were retrospectively reviewed in order to determine long-term survival, event-free survival, and functional outcome resulting after radical resection and to assess the impact of histological grading on outcome. Tumors were located in the cerebral hemisphere in 19 cases, the spinal cord in 30, and the brain stem in nine. Forty-four patients had gross total resection and 14 had radical subtotal resection. Only six patients underwent postoperative irradiation or chemotherapy and, therefore, the outcome was generally related to surgery alone. Of the 58 gangliogliomas, 40 were classified as histological grade I, 16 were grade II, and two were grade III. The median follow-up period was 56 months. There were no operative deaths, and the operative morbidity rate was 5%, 37%, and 33% for cerebral hemisphere, spinal cord, and brain-stem gangliogliomas, respectively. The 5-year actuarial survival rates for cerebral hemisphere, spinal cord, and brain-stem gangliogliomas were 93%, 84%, and 73%, respectively (p = 0.7). The event-free survival rate at 5 years was 95% for cerebral hemisphere gangliogliomas and 36% for spinal cord gangliogliomas (p < 0.05); for brain-stem gangliogliomas the event-free survival rate at 3 years was 53% (p < 0.05). Neurological function at recent follow-up evaluation was stable or improved in 81% of patients. Multivariate analysis (Cox linear regression) revealed tumor location to be the only variable predictive of outcome, with spinal cord and brain-stem gangliogliomas having a 3.5- and 5-fold increased relative risk of recurrence, respectively, compared to cerebral hemisphere gangliogliomas. Histological grade was not predictive of outcome, although in each location there was a trend for higher-grade tumors to have a shorter time to recurrence. It is concluded that radical surgery leads to long-term survival of patients with gangliogliomas, regardless of location, and adjuvant therapy can probably be reserved for special cases.

Adolescent↗
PubMed1993

Management of patients with intramural hematoma of the thoracic aorta.

BACKGROUND: Intramural hematoma of the thoracic aorta (IMH) is a diagnosis of exclusion and represents spontaneous, localized hemorrhage into the wall of the thoracic aorta in the absence of bona fide aortic dissection, intimal tear, or penetrating atherosclerotic ulcer. This process may arise from primary vasa vasorum hemorrhage within the aortic media or rupture of an atherosclerotic plaque. The clinical presentation of patients with IMH mimics that of acute aortic dissection; moreover, considerable diagnostic confusion exists despite the use of many different imaging modalities. The optimal mode of management of patients with IMH (medical versus medical plus surgical) remains problematic because of the paucity of information available. METHODS AND RESULTS: Thirteen patients with IMH were managed at two medical centers between 1983 and 1992. Patients with IMH caused by giant penetrating atherosclerotic ulcers were specifically excluded. There were 8 women and 5 men (mean age, 70 years [range, 54 to 82 years]). The admitting clinical diagnosis was acute aortic dissection, and all patients had a history of hypertension. There was no evidence of aortic dissection or intimal disruption as assessed by computed tomographic (CT) scan (n = 11), aortography (n = 10), magnetic resonance imaging (MRI) scan (n = 9), transesophageal echocardiography (TEE) (n = 6), or intravascular ultrasound (n = 1). The diagnosis of IMH was established by exclusion. The descending thoracic aorta was involved in 10 cases and the ascending/arch in 3. Conservative medical management was attempted initially. All 3 patients with IMH involving the ascending aorta ultimately required operative intervention, and 2 individuals died; 2 of 10 patients with descending aortic involvement eventually underwent surgery. Average hospital stay was 11 days; the mean follow-up interval for discharged patients was 29 months. CONCLUSIONS: IMH is a distinct pathological entity, should not be confused with aortic dissection, and probably will be identified more frequently in the future. All patients with IMH should be monitored carefully and treated with aggressive antihypertensive therapy. Frequent serial assessment is necessary using TEE or MRI/CT scans. Based on this small experience, patients with ascending/arch IMH, ongoing pain, or IMH expansion should probably undergo early graft replacement. Patients with IMH involving the descending thoracic aorta who have no evidence of progression and become pain free can probably be treated conservatively but require antihypertensive therapy and serial aortic imaging surveillance indefinitely.

Aged↗
PubMed1993

Randomized, prospective assessment of bioprosthetic valve durability. Hancock versus Carpentier-Edwards valves.

BACKGROUND: Although the major limitation of porcine valves is their finite durability, no controlled clinical data exist regarding the relative durability of the two porcine bioprostheses implanted most commonly today, the Carpentier-Edwards (C-E) and Medtronic Hancock I (H) valves. METHODS AND RESULTS: To assess this question, 174 patients undergoing aortic (AVR) or mitral (MVR) valve replacement with a bioprosthesis between March 1980 and March 1982 were randomized to receive either a C-E or a H valve. There were 102 AVRs (54 C-E and 48 H) and 74 MVRs (39 C-E and 35 H). For both the AVR and MVR cohorts, the average patient age was 58 +/- 14 years (+/- SD). The male/female ratio was 2.2:1 for AVR and 0.57:1 for MVR. Clinical follow-up was undertaken periodically; the most recent follow-up closing interval was July through October 1992, and current follow-up was 96% complete. Cumulative follow-up totaled 1369 patient-years (mean, 7.7 +/- 3.6 years; median, 9.1 years; maximum, 12.0 years). The main focus of this analysis was bioprosthetic durability, using the AATS/STS guidelines defining "Structural Valve Deterioration" (SVD). Multivariate analysis revealed that (younger) age was the only significant (P = .024) independent predictor of SVD. Valve manufacturer (C-E versus H) and valve site (aortic versus mitral) did not emerge as significant independent risk factors for SVD. Actuarial rates (Cutler-Ederer) expressed as percent free of SVD (+/- SEM) at 10 years (n = number of patients remaining at risk) were 71 +/- 7% and 59 +/- 9% for the C-E (n = 26) and H (n = 17) groups, respectively, for the AVR cohort; for the MVR cohort, these estimates were 60 +/- 10% (n = 12) and 72 +/- 10% (n = 11), respectively, but these differences were not statistically significant (P = NS, Lee-Desu). CONCLUSIONS: After 10 years, there was no statistically significant difference in durability or other valve-related complications between the H and C-E aortic or mitral valves. Based on current information, the choice of a porcine bioprosthesis should be based on factors other than durability, including ease of implantation, hemodynamic performance, and cost.

Aortic Valve↗
PubMed1993

Dilatation of the lateral part of the transverse fissure of the brain in Alzheimer's disease.

Post-mortem MRI (magnetic resonance images) studies followed by histopathological examination were used to study the size and the shape of the lateral part of the transverse fissure of the brain in seven individuals with Alzheimer disease (AD) and five controls. In control brains, the lateral part of the transverse fissure is a narrow cleft protruding laterally as choroid and hippocampal recesses. In AD-affected brains, the lateral part of the transverse fissure becomes a large subarachnoid space as a result of different degrees of atrophy of various hippocampal and parahippocampal structures. Our findings directly indicate the relationship between changes in the hippocampal and parahippocampal structures and the size of the lateral part of the transverse fissure. Sector CA1, the subiculum, the entorhinal cortex, and the parahippocampal isocortex are the most affected, whereas the dentate gyrus is much less affected. Adjacent thalamic structures, which are less vulnerable to the AD pathology, do not appear to contribute to transverse fissure changes. The size and the shape of the lateral part of the transverse fissure of the brain in AD reflect the atrophy of the hippocampus and parahippocampal structures.

Aged↗
PubMed1993

The use of endovascular techniques for the treatment of complications of aortic dissection.

Intravascular ultrasonography, balloon angioplasty, stent placement, and endovascular septal fenestration have been used in the evaluation and treatment of vascular complications of acute and chronic aortic dissection in five patients. There were three men and two women with an average age of 52 years (range 39 to 64 years). There were three chronic type A dissections, one acute type B, and one subacute type B dissection. Intravascular ultrasonography was used in all five cases. The three patients with chronic type A dissections underwent unilateral renal artery angioplasty (RA PTA) and stent placement; one patient with an acute type B dissection and associated fibromuscular dysplasia underwent bilateral RA PTA without stent placement. These procedures were performed to ameliorate severe hypertension. The final patient, with a subacute type B dissection, underwent iliac artery stenting to correct severe lower extremity ischemia. During a second intervention, this patient, who also had bowel ischemia and nonresolving acute renal failure, underwent balloon dilatation of a preexisting septal fenestration to augment visceral blood supply and bilateral RA PTA and stent placement in an effort to improve renal function. This patient eventually died of gut ischemia. After RA PTA and stent placement, one patient had a major intrarenal hemorrhage that required coil embolization and transfusion. In the four survivors, RA PTA and stent placement resulted in immediate improvement in blood pressure control. This response has been sustained during follow-up intervals ranging from 8 to 18 months (average 10 months). Intravascular ultrasonography can clearly demonstrate the pathologic anatomy associated with aortic dissection (even when angiography is ambiguous) and is essential for guiding therapeutic endovascular interventions. Further exploration of the efficacy of these endovascular techniques is warranted in this high-risk group of patients with aortic dissection who have appropriate clinical indications.

Acute Disease↗
PubMed1993

Utilization of manufacturers' implant card data to estimate heart valve failure.

Heart valve manufacturers possess the most complete inventory of world-wide mechanical valve failures, but to convert failures to time-related risks requires estimates of patient follow up. Since manufacturers did not actively track patients, they needed a model that incorporates an assumed death rate to decrease the numbers of patients at risk. We present a method for using a manufacturer's implant card database to estimate time-related complication rates for patient subsets, and illustrate its use by examining the risk of outlet strut fracture (OSF) with the Björk-Shiley 60 degrees Convexo-Concave valve (CC60). We developed a parametric model for valve patient survival based on actively followed valve patients from three centers using only variables typically available from implant cards. Using this survival model, a simulated lifetime was produced for each valve in the CC60 implant database for which the required covariates were known. These lifetimes were then used to analyze OSF as if they were true follow up times. This allowed the use of conventional methods of univariate and multivariate analysis for OSF, including parametric statistical models. According to the approximate linearity of the cumulative hazard functions, OSF risk over time appeared to be fairly constant. Several risk factors were identified, including valve size, patient age at implant and valve position. Using parametric models for both patient survival and OSF permits the estimation of the probability of OSF before death for an individual patient (as opposed to the usual actuarial probability of OSF given that the patient does not die). Because the patient may die before his valve would have failed, this cumulative incidence of OSF is always less than the actuarial risk. For all but the very highest risk patients, the cumulative incidence over their relatively short remaining lifetimes is very small.

Actuarial Analysis↗
PubMed1993

Three-dimensional spiral computed tomographic angiography: an alternative imaging modality for the abdominal aorta and its branches.

PURPOSE: We sought to apply a new technique of computed tomographic angiography (CTA) to the preoperative and postoperative assessment of the abdominal aorta and its branches. METHODS: After a peripheral intravenous contrast injection, the patient is continuously advanced through a spiral CT scanner, while maintaining a 30-second breath-hold. Thirty-five patients with abdominal aortic, renal, and visceral arterial disease have undergone CTA. RESULTS: Diagnostic three-dimensional images were obtained in patients with aortic aneurysms (n = 9), aortic dissections (n = 4), and mesenteric artery stenoses (n = 4). The technique has also been used to assess vessels after operative reconstruction or endovascular intervention in 18 patients. These preliminary studies have correlated well with conventional arteriographic findings. In aneurysmal disease both the lumen and mural thrombus and associated renal artery stenoses are visualized. The true and false channels of aortic dissections and the perfusion source of the visceral vessels are clearly shown; patency of visceral and renal reconstruction or stent placement are confirmed. CTA is relatively noninvasive and can be completed in less time than conventional angiography with less radiation exposure. CONCLUSIONS: This initial experience suggests that CTA may be a valuable alternative to conventional arteriography in the evaluation of the aorta and its branches.

Adult↗