Uptake of inert microparticles in normal and immune deficient mice.

Intestinal microparticle uptake is important for drug delivery, environmental pollution and multiple organ dysfunction syndrome. This paper explores further whether uptake occurs at mucosa associated lymphoid tissue (MALT) via the microfold (M) cells of Peyer's patch domes or through villous epithelium. It does this by comparing the results of exposure of either severe combined immunodeficient (SCID) mice (lacking MALT) or normal BALBc mice, to oral gavage with 2 microm fluorescent latex microparticles. At 5 and 30 min after gavage, full circumference samples along the small intestine were processed for fluorescence microscopy and microparticle numbers were collected for surface and tissue sites. Uptake occurred in both BALBc and SCID mice within 5 min of particle administration and increased further in the following 25 min. In BALBc mice, almost all particles (96%) are in non-MALT sites in MALT circumference samples, with very few at the domes: uptake was also substantial in entirely villous samples. In SCID mice, particle numbers were only slightly lower than those of the BALBc mice, and occurred exclusively by the villous route. These findings confirm that the villous uptake route must be considered when assessing the extent of the dose delivered following pharmaceutical or toxicological oral exposure to microparticles.

Parameters influencing intestinal epithelial permeability and microparticle uptake in vitro.

The hypothesis that, in vivo in situ, villous uptake of 2 microm latex microparticles involves changes at enterocyte tight junctions (TJs) was tested using Caco-2 cells on porous membranes. Epithelial permeability was measured by transepithelial resistance (TER) and particle numbers in surface, intraepithelial and sub-epithelial compartments by microscopy. Apical particle or medium addition initially closed TJs, but this was subsequently reversed in particle-treated groups. Peristaltic onward movement of a bolus was simulated by removing apical particles after an exposure period and leaving the remaining particles to interact with the epithelium: this produced marked TJ loosening during the interaction period. For particle exposure groups, the early similarity with particle numbers in vivo taken up in young adult rats became less marked with time, although bolus removal counteracted this tendency. The TJ response to vasoactive intestinal polypeptide (VIP) was time-dependent. Adsorbed and intraepithelial particle numbers increased with particle exposure time; epithelial-associated microparticle aggregation varied with treatment and submembranous particles were seen in all groups. Correlation between TER changes and particle numbers suggests TJ loosening may be important in microparticle uptake. This Caco-2 model gives epithelial particle numbers that approximate well to published figures for microparticle uptake in vivo and allows effective microenvironmental manipulation.

Factors influencing intestinal microparticle uptake in vivo.

The aim of this study is to compare microparticle uptake in animals of different ages, gender and species and at different time points. The 2mum latex/in vivo in situ model uses the observation of animal responses or post-mortem changes and also particle identification by fluorescence microscopy in nine sequential intestinal segments and secondary sites. The wide size range of animals studied requires particle numbers in tissue compartments to be related to intestinal tissue section area through a circumference measurement. Area under the curve (AUC) data for particles in intestinal tissue are plotted against measurements of intestinal length, allowing comparisons to be made across different ages and species and between males and females. The percentage uptake of administered dose and particle numbers in macerated tissue are also reported. Some parameters, in particular species, do not appear to affect the extent of microparticle uptake, which ranges from 0.12 to 0.32% of the administered dose. Particle uptake does, however, vary with age, being significantly greater in young adult males (7 weeks) than in younger (3 weeks) and older (17 and 52 weeks) age groups. It is concluded that age is more important in determining the extent of uptake than gender or species.

Incidence and histologic characteristics of blebs in patients with abdominal aortic aneurysms.

PURPOSE: Aortic blebs-focal outpouchings within aortic aneurysms-may contribute to their eventual rupture. In this study we determine the incidence of aortic blebs and describe their microscopic features. METHODS: Computed tomographic scans of the abdominal aorta were obtained in 188 patients with aortic diameters measuring > or = 3 cm and were independently evaluated by a radiologist. The number and location of blebs were recorded, and each was measured with calipers. Sixteen blebs, with an adjacent uninvolved aneurysmal segment of aorta, and tissue from two patients with ruptured aneurysms were examined by light microscopy and immunohistochemical analysis. Specimens from six blebs and five aneurysms were examined for alpha 1 (I) procollagen messenger RNA by in situ hybridization. RESULTS: Twenty blebs, ranging in size from 5 to 30 mm (mean, 12 +/- 7 mm), were detected in 11% (20 of 188) of computed tomographic scans. Blebs were observed in 10% (11 of 111) of patients with aortic diameters between 3.0 and 4.9 cm, 10% (6 of 61) of patients with aneurysms between 5.0 and 6.9 cm, and 19% (3 of 16) of patients with aortic diameters > or = 7 cm. Histologically, the major difference between the aneurysmal aortic wall and blebs was found in the media. In aneurysmal aortas, the media consisted of multiple layers of fragmented elastic lamellae, whereas the number of elastic tissue elements along the circumference of the blebs progressively decreased; only a few isolated fragments of elastic tissue were present at the apices. Histologic evidence of rupture was evident in two specimens. A chronic inflammatory cell infiltrate composed of T and B lymphocytes, plasma cells, and macrophages, common to both the aneurysmal and the blebs, was most prominent in the adventitia of aneurysmal tissue, but involved both the media and adventitia of the blebs. In situ hybridization demonstrated the presence of alpha 1 (I) procollagen messenger RNA in four of the five aneurysm segments that were evaluated, compared with only one of six blebs. CONCLUSIONS: Blebs were discovered in aneurysms of all sizes; their frequency appeared to be unrelated to aneurysm size. The presence of inflammatory cell infiltrates and absence of alpha 1 (I) procollagen messenger RNA in five of six blebs suggest that a local imbalance of matrix degradation and repair plays a role in the cause of these lesions. Attenuation of the aortic wall accompanying the formation of blebs may predispose these sites to rupture.

Abdominal wall hernias in patients with abdominal aortic aneurysmal versus aortoiliac occlusive disease.

BACKGROUND: This study was undertaken to determine the incidence of ventral incisional hernias (VIHs) and inguinal hernias (IHs) in patients with abdominal aortic aneurysmal (AAA) versus those with aortoiliac occlusive disease (AIOD). PATIENTS AND METHODS: The medical records of 193 patients (128 with AAA and 65 with AIOD) who had undergone elective aortic reconstruction were reviewed to determine the number and location of abdominal wall hernias (AWHs). RESULTS: Forty-one AWHs (28 IHs and 13 VIHs) were detected in patients with AAA compared to 13 (11 IHs and 2 VIHs) in patients with AIOD. There was a significantly greater incidence of VIHs in patients with AAA versus patients with AIOD (10% versus 3%, P < 0.05) and recurrent AWHs (28% versus 19%, P < 0.01), but not of IHs (22% versus 17%). CONCLUSION: Patients with AAA have a higher incidence of VIHs and recurrent AWHs--without a corresponding increase in patient-related risk factors--than patients without aneurysm, suggesting that as yet unidentified etiologic factors may contribute to the development of AWHs in these patients.

Pulmonary embolism following hemodialysis access thrombolysis/thrombectomy.

PURPOSE: The increased use of thrombectomy with deliberate pulmonary embolization of thrombus following initial thrombolysis for occluded hemodialysis fistulas prompted the authors to measure the prevalence of pulmonary embolism (PE) due to the procedure. PATIENTS AND METHODS: Thirty-one patients with 43 acutely thrombosed polytetrafluoroethylene hemodialysis fistulas were treated with thrombolysis/thrombectomy. Perfusion lung scans were obtained in 22 patients. Patients were also continuously monitored for clinical signs or symptoms of PE. RESULTS: Perfusion scans were interpreted as consistent with PE in 59% of those studied, but no clinical signs or symptoms were present in 41 of the 43 cases (95%). However, two patients developed both signs and symptoms of acute PE in the postprocedural period and died. One had underlying pulmonary disease and had undergone thrombectomy before. The other had chronic heart disease. CONCLUSION: Thrombolysis/thrombectomy is usually safe and effective, even though many patients develop subclinical PE. The authors urge extreme caution in patients who have underlying pulmonary or cardiac disease and/or have undergone the procedure before.

Application of computed tomography for surveillance of aortic grafts.

BACKGROUND: This study was undertaken to assess the application of computed tomography (CT) for surveillance of aortic grafts. METHODS: Demographics, operative technique, and graft type and size at the time of implantation of aortic grafts in 178 patients were recorded. CT measurements of graft diameters were made with calipers. Data were analyzed by analysis of variance, multiple regression, and chi-squared methods. RESULTS: One hundred twenty-eight (72%) bifurcated grafts and 50 (28%) tube grafts were placed for aneurysmal disease (49%), aortoiliac occlusive disease (47%), ruptured aneurysm (2.3%), anastomotic aneurysm (1%), and graft aneurysm (0.6%). Mean implant time was 43.3 +/- 3.2 months. A total of 143 Dacron prostheses (74 woven, 69 knitted) and 35 polytetrafluoroethylene prostheses were placed. Mean percentage dilation was 49.2 +/- 4.0 for knitted prostheses, 28.5 +/- 3.0 for woven prostheses, and 20.6 +/- 1.9 for polytetrafluoroethylene prostheses compared with the graft implant size. A significant correlation was seen between graft dilation (more than 50%) and graft construction with knitted prostheses (p < 0.01, Tukey's range test). Complications detected by CT occurred in 24 (13.5%) patients including supragraft aneurysms (seven), distal anastomotic aneurysms (five), proximal anastomotic aneurysms (three), graft infections (two), perigraft fluid collections (two), graft aneurysm with thrombus and distal embolization (two), and nonvascular complications (three). CONCLUSIONS: CT is a useful modality for postoperative imaging of aortic prostheses. Routine surveillance may detect complications before they become clinically apparent.

Contrast-induced nephrotoxicity: the effects of vasodilator therapy.

The increasingly frequent use of contrast-enhanced imaging for diagnosis or intervention in patients with peripheral vascular disease has generated concern about the incidence and avoidance of contrast-induced nephrotoxicity (CIN). In this prospective study, we sought to identify those patients at greater risk of developing CIN and to evaluate the efficacy of vasodilator therapy with dopamine in limiting this complication. Baseline serum creatinine (Cr) concentrations were obtained on admission and daily for up to 72 hr after angiography in 222 patients undergoing 232 angiographic procedures. The preangiographic treatment was varied at 2-month intervals for 1 year. All patients received an intravenous infusion of 5% dextrose and 0.45% normal saline at a rate of 75 to 125 ml/hr. During the first interval patients received 12.5 g of 25% mannitol immediately prior to their contrast load, in addition to intravenous fluids. During the next 2-month period the patients were given renal dose dopamine intravenously (3 micrograms/kg/min) commencing the evening before angiography and continued to the next morning. During the latter half of the study the treatment regimens were modified so that the use of mannitol was restricted to patients with diabetes mellitus and dopamine to patients with serum creatinine concentrations of > or = 2 mg/dl. Postangiographic elevation in Cr occurred in 2, 10.4, and 62% of studies in patients with baseline creatinine levels of < or = 1.2 mg/dl, 1.3 to 1.9 mg/dl, and > or = 2.0 mg/dl, respectively. None of the patients receiving dopamine experienced an elevation in creatinine. There was no statistical correlation between age, diabetes, or medication with calcium channel blockers and CIN.(ABSTRACT TRUNCATED AT 250 WORDS)

Proximity injuries: correlation with results of extremity arteriography.

The results of 170 emergency arteriography procedures in 142 patients who had sustained extremity injuries near major arteries were correlated with the findings from a physical examination conducted prior to arteriography. Radiographically demonstrable significant arterial injuries, which usually required surgical repair, were present at 42 of the 170 injury sites (25%). Major physical findings suggestive of arterial injury were noted at 105 of 170 sites (62%). Arteriography demonstrated a significant injury in 40 (38%) of these 105 injury sites, representing 95% of all major arterial injuries. Among the 65 injury sites without any suggestive major physical finding, only two were associated with a significant vascular injury at arteriography (3%) (5% of all 42 arterial injuries). At each of these 65 injury sites, the decision to perform emergency arteriography was based solely on the proximity of the wound to a major artery. In spite of this very low yield in the subgroup of 51 patients without major physical findings, emergency arteriography is still routinely requested for extremity injuries at the authors' institutions. The validity of this policy, a possible reason for its development, and its effect on patient disposition are examined.