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Biomedical subjects

M J Post

Publications and source records attributed to M J Post.

At least 37 records · Page 2Linked to original sources

The atherosclerotic Yucatan animal model to study the arterial response after balloon angioplasty: the natural history of remodeling.

OBJECTIVE: Remodeling in de novo atherosclerosis and in restenosis after balloon angioplasty constitutes a change in total arterial circumference which, together with plaque growth or neointimal formation, determines the lumen of the artery. To better understand the fundamental biology of neointimal formation, remodeling and their interaction, animal studies are needed. In this study, we described in detail the methodology used and the natural history of neointimal formation and remodeling after balloon angioplasty in atherosclerotic Yucatan micropigs. METHODS AND RESULTS: Atherosclerosis was induced in 60 peripheral arteries of sixteen Yucatan micropigs by a combination of denudation and atherogenic diet. Balloon angioplasty was performed in 38 arteries, with serial intravascular ultrasound (IVUS) and quantitative angiography before and after intervention and at 2, 4, 7, 14 or 42 days follow-up. Remodeling, expressed as late media-bounded area (MBA) loss, increased progressively over time. At 42 days, late MBA loss after balloon angioplasty was significantly different compared to late MBA loss in control arteries, 2.2 +/- 1.0 versus -0.3 +/- 1.1 mm2 and p = 0.02. Late lumen loss increased over time and was highest at 42 days after balloon angioplasty (2.8 +/- 0.7 mm2). The contribution of neointimal formation to late lumen loss decreased over time and the contribution of late MBA loss to late lumen increased over time and was highest at 42 days (78%). Medial necrosis was 48% at two days after balloon angioplasty and the repopulation of the media was almost completed at seven days. CONCLUSION: Remodeling following balloon angioplasty has an early onset and progresses with neointimal formation to cause restenosis over the standard 42-day time course for Yucatan micropigs. This correlates to six months renarrowing in humans. In this model, atherosclerosis and the natural history of restenosis, both with respect to neointimal formation and remodeling, resemble the human disease quite closely.

Analysis of Variance↗

The relation between de novo atherosclerosis remodeling and angioplasty-induced remodeling in an atherosclerotic Yucatan micropig model.

Geometric remodeling in de novo atherosclerosis and in restenosis after balloon angioplasty constitutes a change in total arterial circumference that, together with plaque growth or neointima formation, determines the lumen of the artery. The heterogeneous nature of arterial obstructions raises the question of whether early and late outcomes (restenosis) of angioplasty are affected by the degree and direction of de novo atherosclerotic remodeling. This study was designed to assess the relationship between atherosclerotic remodeling and the degree and mechanism of restenosis after balloon angioplasty. Atherosclerosis was induced in 27 peripheral arteries of 18 Yucatan micropigs by a combination of denudation and atherogenic diet. Balloon angioplasty was performed, with serial intravascular ultrasound and quantitative angiography before and after intervention and at 42 days' follow-up. We used the relative media-bounded area (MBA), defined as the MBA of the treated site divided by the MBA of the reference, before angioplasty as a measure of remodeling in de novo atherosclerosis and late MBA loss as a measure of remodeling after balloon angioplasty. Relative MBA before angioplasty was not correlated with angiographic and echographic acute gain after balloon angioplasty (r=.22, P=.28 and r=.14, P=.48) or with late lumen loss (r=-.05, P=.81 and r=.19, P=.33). No correlation was found between relative MBA and late MBA loss (r=.14 and P=.48). In the atherosclerotic Yucatan micropig, remodeling during de novo atherosclerosis has no relevance for acute gain and late lumen loss after balloon angioplasty. Both the direction and the extent of remodeling after balloon angioplasty are not related to the direction and extent of remodeling during de novo atherosclerosis.

Angiography↗

Cerebral aneurysmal arteriopathy in childhood AIDS.

OBJECTIVE: To identify cerebral aneurysmal arteriopathy in children with longstanding AIDS. BACKGROUND: Five cases are described from the authors' experience, and eight additional cases are reviewed from the literature. Details are presented in regard to the clinical picture as well as brain imaging with cerebral angiography and magnetic resonance angiography in some cases. Autopsy information is available in four cases, including one of the authors' patients. RESULTS: Seven patients acquired HIV infection perinatally, five patients were infected by blood transfusions, and one patient had both risk factors. In the four postmortem patients, the vascular pathology was similar, showing ectasia and aneurysmal dilatation confined to the large arteries of the circle of Willis. Medial fibrosis and loss of muscularis with destruction of the internal elastic lamina and intimal hyperplasia was common. The latency period following infection varied from 2 to 11 years. Once a diagnosis of aneurysmal arteriopathy was made, the patients deteriorated rapidly, with death occurring in less than 6 months. CONCLUSIONS: The development of cerebral aneurysmal arteriopathy in childhood AIDS tends to occur after a prolonged delay and is usually followed by death in a short period of time. The etiology for the vasculitis is unknown. Varicella zoster virus may be the etiology in some of the cases because of its potential to cause this pathology and the striking unilateral arterial involvement found in Case 5. HIV vasculitis is also a possibility, as suggested by the detection of HIV protein or genomic material in two of the four autopsy cases.

Acquired Immunodeficiency Syndrome↗

Arterial remodeling after balloon angioplasty or stenting in an atherosclerotic experimental model.

BACKGROUND: Recent studies have indicated that coronary restenosis after balloon angioplasty is the sum of geometric remodeling and neointimal formation. A proportional relationship between acute gain and late lumen loss has been observed in clinical trials. The aims of this study were to evaluate (1) the contribution of geometric remodeling and neointimal formation to the proportional gain-loss relationship after PTA or stenting and (2) the relationship between geometric remodeling and neointimal formation. METHODS AND RESULTS: In atherosclerotic iliac arteries of 29 Yucatan micropigs, PTA or stenting was performed, with serial intravascular ultrasound (IVUS) and quantitative angiography before and after intervention and at 2 or 42 days of follow-up, followed by histomorphometrical analysis. For PTA at 42 days, late lumen loss by IVUS correlated strongly with geometric remodeling, expressed as late media-bounded area (MBA) loss (R2=.843, P<.001, n=20), and correlated weakly with intimal hyperplasia area (R2=.214, P=.02). For stented arteries, however, late lumen loss correlated moderately with intimal hyperplasia (R2=.367, P=.01, n=18) and only weakly with geometric remodeling (R2=.195, P=.04). Late lumen loss and late MBA loss of reference segments were observed at 42 days, especially in PTA arteries. Intimal hyperplasia and geometric remodeling were not correlated. CONCLUSIONS: In this experimental model, the proportional relationship between acute gain and late lumen loss is mainly due to the proportional relationship between acute gain and geometric remodeling for PTA and between acute gain and intimal hyperplasia for stents. Finally, neointimal formation and remodeling seem to be unrelated processes.

Angiography↗

Impact of local atherosclerotic remodeling on the calculation of percent luminal narrowing.

The choice of the reference site in order to calculate percent luminal narrowing mainly depends on which diagnostic tool is used for examination. In intravascular ultrasound or histology, the local area encompassed by the internal elastic lamina (IEL) area is used as a reference. However, the local IEL area, and thereby the reference value, may have been altered by atherosclerotic remodeling. In the present study we examined the impact of local arterial remodeling on the calculation of luminal narrowing. Forty-five human femoral arteries were analyzed, 32 postmortem and 20 in vivo, by intravascular ultrasound. Cross sections were examined every 0.5 cm over an arterial segment length of 10 to 15 cm. In each cross section we measured the lumen area and the IEL area. Two reference areas were used to calculate percent luminal narrowing: (1) the lumen area in the cross section that contained the least amount of plaque (distant reference); and (2) the local IEL area (local reference). In each cross section, the IEL area was expressed as percent of the IEL area in the cross section that contained the least amount of plaque (relative IEL area). Using the distant reference, we found that less luminal narrowing was observed for cross sections with a relative IEL area > 100% (indicating compensatory enlargement) than for those with a relative IEL area < 100% (indicating shrinkage), whereas percent luminal narrowing calculated using the local reference hardly differed between cross section with a relative IEL area > 100% and < 100%. Thus, arterial wall remodeling makes the local IEL area an unreliable reference for calculation of percent luminal narrowing. The calculated percent luminal narrowing using a distant, nondiseased reference site reflects the actual change of the luminal area more accurately.

Aged↗

Effects of hypercholesterolemia on the contractions to angiotensin II in the isolated aorta and iliac artery of the rabbit: role of arachidonic acid metabolites.

The aim of this study was to investigate the effect of hypercholesterolemia on the angiotensin II-induced contractions in the isolated aorta and iliac artery of the rabbit, with respect to the role of arachidonate metabolites. Furthermore, the effect of the angiotensin-converting enzyme inhibitor ramipril was studied on the responses to angiotensin II in the cholesterol-fed rabbit. After 12 weeks of cholesterol diet (0.3%), endothelium-dependent relaxations to acetylcholine were significantly fewer compared with control (30.2 +/- 5.9% vs. 73.0 +/- 1.7%) in the aorta but not in the iliac artery of the rabbit. The angiotensin II- and methoxamine-induced contractions were also significantly lower compared with control in the aorta (101.4 +/- 6.7% vs. 60.9 +/- 4.2% and 160.2 +/- 5.7% vs. 135.8 +/- 8.0%, respectively) but not in the iliac artery. The lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) selectively attenuated the angiotensin II-induced contractions in rabbit aortic rings from the control group only in the presence of the endothelium, whereas it had no effect on the responses to angiotensin II in the cholesterol group (with or without endothelium). In the iliac artery, NDGA inhibited the responses to angiotensin II in both the control and cholesterol groups. Treatment with ramipril (0.33 mg/kg/day) significantly improved the maximal angiotensin II-induced contraction in the aorta of rabbits fed a cholesterol diet for 16 weeks to 61.0 +/- 7.3% (vs. 32.7 +/- 9.0% in the cholesterol group). We conclude that hypercholesterolemia leads to a reduction of angiotensin II-induced contractions in the aorta and not in the iliac artery of the rabbit. This reduction might be related to loss of endothelium-dependent lipoxygenase products and is partially reversed by ramipril.

Angiotensin II↗

Relationship between plaque mass and neointimal hyperplasia after stent placement in Yucatan micropigs.

PURPOSE: To determine whether the amount of neointima found after stent placement is related to the preexistent plaque mass in the peripheral arteries in micropigs. MATERIALS AND METHODS: Twenty-six peripheral arteries were studied in 14 Yucatan micropigs in a denudation and diet-induced atherosclerosis model. Quantitative angiographic and intravascular ultrasound (US) analysis were performed before and after stent placement and at follow-up 6 weeks after stent placement. At follow-up, the peripheral arterial tree was fixed by means of pressure perfusion, processed for histologic analysis, and analyzed morphometrically with a computer-based system. RESULTS: Preexistent plaque correlated strongly with intimal hyperplasia measured on US images (r = .81, P < .001) or in histologic sections (r = .53, P = .006). No correlation was found between dilation ratio and intimal hyperplasia or between balloon-to-lesion ratio and intimal hyperplasia. In multivariate models of intimal hyperplasia, preexistent plaque and early gain in lumen diameter depicted at angiography were independent explanatory variables. CONCLUSION: The amount of plaque present before stent placement was a determinant of the amount of intimal hyperplasia present after stent placement.

Angiography↗

Primary central nervous system lymphoma in patients with AIDS.

Primary central nervous system lymphoma (PCNSL), once considered a rare brain neoplasm, has been steadily increasing in incidence mainly due to an enlarging population of immunosuppressed patients. PCNSL has become the second most common brain space occupying lesion in patients with the acquired immunodeficiency syndrome. A rapid diagnosis of this entity may represent weeks to months of survival to immunosuppressed HIV-positive patients. The radiologist now plays an important role in the noninvasive diagnosis and management of this condition through the accurate interpretation of imaging findings provided by CT, MR, and brain SPECT studies. This article focuses on the pathogenesis, clinical manifestations, neuropathology, and imaging characteristics of this brain neoplasm. New accurate imaging algorithms combining the diagnostic information provided by CT, MR, and T1-201 brain SPECT are discussed.

Brain↗

Diagnostic imaging of infections and neoplasms affecting the spine in patients with AIDS.

The central nervous system may be affected by AIDS in the form of infections or neoplasia and by HIV itself. The spine and spinal cord are involved more commonly than documented. MR imaging is the most sensitive imaging technique for the detection of AIDS-related abnormalities in the spine and spinal cord. The early detection by spinal imaging will allow the prompt initiation of the appropriate therapy.

AIDS-Related Opportunistic Infections↗

Spinal cord lesions in patients with AIDS.

In the past, little attention has been given in the imaging literature to spinal cord findings in the human immunodeficiency syndrome. This article summarizes the major pathologic conditions found in the spinal cord in patients with AIDS and compares them to MR features. The details of toxoplasma myelitis, spinal cord lymphoma, HIV myelitis, and tract pallor are demonstrated. A review of literature and a description of the pathologic cord changes will help the reader understand the alterations of the spinal cord in patients with AIDS.

AIDS-Related Opportunistic Infections↗

Atherosclerotic arterial remodeling in the superficial femoral artery. Individual variation in local compensatory enlargement response.

BACKGROUND: In previous studies on atherosclerotic arterial remodeling, compensatory enlargement of the artery in response to plaque accumulation was inferred from pooled data based on one cross section per artery. We assessed local arterial remodeling individually by analyzing 45 artery segments at 0.5-cm intervals over a length of 10 to 15 cm. METHODS AND RESULTS: Twenty patients were studied by 30-MHz intravascular ultrasound (IVUS) before balloon angioplasty of the superficial femoral artery (370 cross sections), and 25 femoral artery segments were studied postmortem (551 cross sections). In each cross section, the area surrounded by the internal elastic lamina (IEL area) and the plaque area were measured. The IEL area was larger in the cross section with the largest plaque area than in the cross section with the smallest plaque area (32.5+/-13.0 and 32.0+/-11.5 mm2 versus 28.9+/-9.7 [P=NS] and 26.7+/-10.1 [P<.05] mm2 for IVUS and histology, respectively [mean+/-SD]). A significant positive correlation was found between plaque area and IEL area for the pooled data (r=.61 and r=.47 and slope=1.07 and 0.90 for IVUS and histology, respectively; both P<.001). In 12 of 20 and 16 of 25 individual arterial segments, however, no significant correlation was observed between plaque area and IEL area for IVUS and histology, respectively. A large variation was found in the correlation of the regression of plaque to IEL area (IVUS, r=-.40 to .89; histology, r=-.13 to .91) and slope (IVUS, -0.28 to 1.29; histology, -0.18 to 1.32). CONCLUSIONS: In the majority of atherosclerotic femoral arteries, significant compensatory enlargement could not be determined. It is inferred that arterial remodeling in response to plaque formation may vary among individuals.

Aged↗

Computation of a location shift between two subsequent intra vascular ultrasound registrations by cross-correlation analysis of the lumen area functions.

For longitudinal studies on atherosclerosis and restenosis after angioplasty by intravascular ultrasound (IVUS), it is essential that repeated studies are performed at exactly the same location along an arterial section. In human femoral arteries, lumen and plaque area functions of two subsequent IVUS pullback maneuvers were compared by cross-correlation analysis. In cross-correlation analysis of two functions with equal abscissa values, the data sets are repetitively correlated after incremental shifts of the two functions along the abscissa. This results in multiple correlation coefficients with a maximum at the relative position where the two functions show the closest match. In group A (12 patients), both pullbacks were performed after angioplasty and in group B (17 patients) one pullback was performed before angioplasty and the second immediately after angioplasty. In group A, cross-correlation showed a shift between lumen area functions of 5 mm in one patient and no shift in the other patients. Maximum correlation coefficients in group A ranged from 0.644 to 0.978. Four patients from group B showed shifts from 2.5 to 35 mm. Maximum coefficients were significantly smaller than in group A: 0.259-0.864 (p < 0.01). Plaque area functions in group B showed higher correlations (0.468-0.862, p = 0.034) and only two shifts. Cross-correlation of lumen and plaque area functions may be used to compute location shifts between two subsequent IVUS registrations and to correct such shifts.

Aged↗

Fogarty and percutaneous transluminal coronary angioplasty balloon injury induce comparable damage to the arterial wall but lead to different healing responses.

PURPOSE: Fogarty balloon denudation in experimental animals often serves as a model for percutaneous transluminal coronary angioplasty (PTCA). We compared the healing response of the arterial wall with the use of Fogarty and PTCA balloon dilation. METHODS: Carotid arteries of rabbits were injured with a 2F Fogarty (n = 9) or a 3 mm PTCA balloon (n = 6). At 1 day endothelial cell removal was qualitatively evaluated in Fogarty balloon lesions and in PTCA balloon lesions with a modified "en face" silver nitrate staining. Medial necrosis was morphometrically determined as percentage medial area. After 21 days endothelial cell coverage was assessed in the center of the lesion with an antibody to CD31 and intimal proliferation with an antibody to the nuclear antigen Ki-67. Intimal hyperplasia area was measured with morphometry. Acute lumen gain directly after Fogarty balloon dilation and PTCA balloon dilation was determined by serial angiography. All data are means +/- SEM. RESULTS: At 21 days intimal hyperplasia area was higher in the Fogarty balloon lesions than in the PTCA balloon lesions. Intimal hyperplasia area was 0.19 +/- 0.02 mm2 and 0.03 +/- 0.01 mm2, respectively. Immediately after injury the acute gain in luminal diameter did not differ between Fogarty and PTCA balloon dilation (0.37 +/- 0.03 mm and 0.38 +/- 0.05 mm, respectively). At 1 day after injury endothelial cell removal was complete in all segments. Medial necrosis caused by Fogarty (67% +/- 7%) and PTCA balloon dilation (74% +/- 9%) did not differ. At 21 days endothelial cell coverage was almost complete both in the Fogarty balloon lesions and in the PTCA balloon lesions. Intimal proliferation was also higher in the Fogarty balloon lesions than in the PTCA balloon lesions. CONCLUSION: Despite comparable endothelial cell abrasion and medial necrosis, Fogarty balloon injury elicited significantly augmented intimal hyperplasia compared with PTCA balloon dilation.

Angioplasty, Balloon, Coronary↗

Interventional thermal injury of the arterial wall: unfolding of von Willebrand factor and its increased binding to collagen after 55 degrees C heating.

PURPOSE: Thermal angioplasty alters the thrombogenicity of the arterial wall. In previous studies, platelet adhesion was found to increase after heating human subendothelium to 55 degrees C and decrease after heating to 90 degrees C. In the present electron microscopic study, the mechanism of this temperature-dependent platelet adhesion to the heated arterial wall is elucidated by investigating temperature-dependent conformational changes of von Willebrand factor (vWF) and collagen types I and III and the binding of vWF to heated collagen. METHODS: Purified vWF and/or collagen was applied to electron microscopic grids and heated by floating on a salt-solution of 37 degrees C, 55 degrees C or 90 degrees C for 15 s. After incubation with a polyclonal antibody against vWF and incubation with protein A/gold, the grids were examined by electron microscopy. RESULTS: At 37 degrees C, vWF was coiled. At 55 degrees C, vWF unfolded, whereas heating at 90 degrees C caused a reduction in antigenicity. Collagen fibers heated to 37 degrees C were 60.3 +/- 3.1 nm wide. Heating to 55 degrees C resulted in the unwinding of the fibers, increasing the width to 87.5 +/- 8.2 nm (p < 0.01). Heating to 90 degrees C resulted in denatured fibers with an enlarged width of 85.1 +/- 6.1 nm (p < 0.05). Heating of collagen to 55 degrees C resulted in an increased vWF binding as compared to collagen heated to 37 degrees C or to 90 degrees C. Incubation of collagen with vWF, prior to heating, resulted in a vWF binding after heating to 55 degrees C that was similar to the 37 degrees C binding and a decreased binding after 90 degrees C. CONCLUSIONS: After 55 degrees C heating, the von Willebrand factor molecule unfolds and collagen types I and III exhibit an increased adhesiveness for von Willebrand factor. Heating to 90 degrees C denatures von Willebrand factor and collagen. The conformation changes of von Willebrand factor and its altered binding to collagen type I and III may explain the increased and decreased platelet adhesion to subendothelium after 55 degrees C and 90 degrees C heating, respectively.

Analysis of Variance↗

MR of vasculitis-induced optic neuropathy.

PURPOSE: To describe the MR characteristics of optic neuropathy caused by vasculitis. METHODS: Nine cases of optic neuropathy with diagnosis of vasculitis (six with systemic lupus erythematosis and one each with rheumatoid arthritis, Sjögren disease, and radiation vasculitis) were reviewed retrospectively. Patients were 31 to 62 years old, and all but one were women. All patients had MR imaging through the orbits and anterior visual pathways, five with fat suppression, with and without gadopentetate dimeglumine. Five patients also had MR imaging of the entire brain. The size and enhancement of various segments of the optic nerve and anterior visual pathways were studied. RESULTS: MR imaging with contrast material showed enhancement and enlargement of segments of the optic nerves and/or chiasm in six of the nine patients (all but three with systemic lupus erythematosis). Enlargement of a segment of the anterior visual pathway never occurred without enhancement, but enhancement alone did occur in three cases. Of the five patients who had MR imaging of the whole brain, abnormalities were seen in three: periventricular hyperintensity in two and a lacunar infarct in one; none had vessel abnormalities. CONCLUSION: Because the MR enhancement seen represents disruption of the blood-brain barrier within the optic nerve, MR imaging with gadopentetate dimeglumine and fat suppression should be performed to detect increased permeability of the blood-brain barrier in acute optic neuropathy.

Adult↗

MR characteristics of histopathologic subtypes of spinal ependymoma.

PURPOSE: To examine MR characteristics and enhancement patterns of spinal ependymomas and compare these data with histopathologic subtypes. METHODS: The MR images from 26 cases of pathologically proved spinal ependymomas were evaluated with respect to seven criteria: signal characteristics, enhancement pattern, length of involvement, cysts or syrinxes, hemorrhage, bony changes, and type of cord expansion. Signal characteristics were then correlated with histologic subtype. RESULTS: In the category of enhancement pattern, our results differed markedly from published data, with only 38% of cases demonstrating classic homogeneous enhancement. The remainder of our cases (62%) demonstrated other enhancement patterns, including heterogeneous (31%), rim (19%), minimal (6%), and no enhancement (6%). Pathologic comparison revealed that one histologic subtype, the myxopapillary ependymoma, demonstrated unique imaging characteristics on T1-weighted images. A highly statistically significant percentage of this variant was hyperintense on T1, whereas most nonmyxopapillary ependymomas were hypointense. CONCLUSION: The radiologist should be aware of alternative patterns of enhancement of spinal ependymomas and not be dissuaded from the diagnosis in appropriate clinical settings. In addition, one histologic subtype, myxopapillary, often exhibits signal characteristics different from nonmyxopapillary types, appearing hyperintense on T1 probably because of their intracellular and perivascular accumulation of mucin.

Adult↗