Joiner Cartwright

Segmental mediolytic arteritis. A clinicopathologic and ultrastructural study of two cases

We describe the histopathologic and ultrastructural changes in two cases of segmental mediolytic arteritis (SMA) and summarize the clinical and pathologic findings in previous reports. SMA is initiated by the transformation of the arterial smooth-muscle cytoplasmic contents into a maze of dilated vacuoles containing edema-like fluid. With vacuolar rupture, the smooth-muscle cells are disrupted and the mediolytic process completed. Mediolysis is accompanied by fibrin deposition and hemorrhages at the adventitio-medial junction and within the media. Inflammation is inconstant and limited to the periadventitial tissues. Transmural mediolysis leads to the formation of arterial wall gaps—defects in the vascular wall bridged by a serofibrinous layer. The serosal and intramural arteries and arterioles of the jejunum and the epicardial coronary arteries were the targets of SMA in this report. SMA occurs in two clinical settings: (a) in abdominal muscular arteries and arterioles of predominantly elderly patients presenting either with ischemic bowel disease or shock, and (b) in the coronary arteries of neonates in conditions associated with severe hypoxemia. We conclude that SMA is the result of an inappropriate vasospastic response expressed in a splanchnic vascular bed undergoing vasoconstriction as a response to shock or severe hypoxemia.

Silicone lymphadenopathy associated with augmentation mammaplasty. Morphologic features of nine cases.

Silicone lymphadenopathy (SL)—defined as the presence of silicone in a lymph node—is a rare side effect of mammary augmentation either by injection of liquid silicone or by placement of a bag-gel prosthesis. Nine new cases in eight patients are herein reported and compared with six previously well-documented cases. The available data showed that SL was frequently detected as an incidental finding of no clinical significance during mastectomy and nodal dissection for associated breast carcinoma (nine cases), but may present as a painful or nontender enlarged lymph node (six cases). The latter presentation was almost always associated with a history of injection of liquid silicone or rupture of the prosthesis. All or some of the following findings were present in an affected lymph node: coarse vacuoles, fine vacuoles, and multinucleated giant cells. All lymph nodes contained a variable amount of an unstained, nonbirefringent, refractile material that, in seven of our cases, was shown to contain elemental silicon by energy-dispersive x-ray elemental analysis. In 312 lymph nodes collected from 18 routine cases of breast carcinoma, coarse vacuoles probably representing fat were found in 107 lymph nodes (34%); focal fine vacuoles were found in one (0.3%), and a single multinucleated giant cell was found in one (0.3%). In conclusion, SL probably will be encountered more frequently when cancer-prone age is reached by the susceptible population. In most cases, it is an incidental finding of no clinical significance. However, the histologic diagnosis can be made by observing characteristic light-microscopic changes, which may be supplemented in doubtful cases by energy-dispersive x-ray analysis.

Decreased necrotizing fasciitis capacity caused by a single nucleotide mutation that alters a multiple gene virulence axis

Single-nucleotide changes are the most common cause of natural genetic variation among members of the same species, but there is remarkably little information bearing on how they alter bacterial virulence. We recently discovered a single-nucleotide mutation in the group A Streptococcus genome that is epidemiologically associated with decreased human necrotizing fasciitis (“flesh-eating disease”). Working from this clinical observation, we find that wild-type mtsR function is required for group A Streptococcus to cause necrotizing fasciitis in mice and nonhuman primates. Expression microarray analysis revealed that mtsR inactivation results in overexpression of PrsA, a chaperonin involved in posttranslational maturation of SpeB, an extracellular cysteine protease. Isogenic mutant strains that overexpress prsA or lack speB had decreased secreted protease activity in vivo and recapitulated the necrotizing fasciitis-negative phenotype of the ΔmtsR mutant strain in mice and monkeys. mtsR inactivation results in increased PrsA expression, which in turn causes decreased SpeB secreted protease activity and reduced necrotizing fasciitis capacity. Thus, a naturally occurring single-nucleotide mutation dramatically alters virulence by dysregulating a multiple gene virulence axis. Our discovery has broad implications for the confluence of population genomics and molecular pathogenesis research.

Inhibitory Effects of Hypercholesterolemia and Ox-LDL on Angiogenesis-like Endothelial Growth in Rabbit Aortic Explants Essential Role of Basic Fibroblast Growth Factor

Hypercholesterolemic (HC) rabbits exhibit suppressed compensatory vascular growth after restriction of arterial supply. However, neovascularization is commonly found in atheromas containing inflammatory cells. We used an in vitro model to determine the effects of hypercholesterolemia on angiogenesis in the absence or presence of inflammatory cells. HC rabbit aortic explants (1 mm2) with or without (n = 90 each) lesion-forming inflammatory cells were cultured in a collagen matrix with serum-free medium. Explant-derived endothelial cell growth was organized into capillary-like microtubes (CLM) that could be videomicroscopically quantified. CLM growth from lesion-free HC explants was significantly reduced to 13 +/- 4% of the value in explants (n = 90) from normocholesterolemic (NC, n = 15) rabbits (P < .001). In contrast, in lesion-containing HC explants, the matrix was invaded by foam cells, and CLM growth was not inhibited. Immunoassayable basic fibroblast growth factor (bFGF, in pg/mL) in the culture medium was significantly lower in lesion-free HC (< 5) than NC explants (11 +/- 2, P < .01) or HC explants with lesions (14 +/- 3). In addition, CLM growth was reduced in NC explants incubated with oxidized LDL (ox-LDL, 50-100 micrograms/mL). Exogenous bFGF (10 ng/mL) reversed the inhibitory effects of hypercholesterolemia and ox-LDL, whereas bFGF-neutralizing antibody (10 micrograms/mL) abolished CLM growth in all groups. In cultured rabbit aortic endothelial cells, ox-LDL reduced DNA synthesis, but this inhibition was reversed by bFGF. We conclude that hypercholesterolemia and ox-LDL inhibit angiogenesis like endothelial growth because of a suppressed availability of endogenous bFGF. Retained responsiveness to exogenous bFGF suggests that inducing bFGF expression at targeted sites may improve collateral growth in hyperlipidemic arterial disease.

Are Gadolinium-Based Contrast Media Nephrotoxic?: A Renal Biopsy Study

Gadolinium-based contrast media were originally introduced as alternatives to iodinated media for magnetic resonance imaging. Although originally thought to be nonnephrotoxic, gadolinium-based contrast media have recently been reported to be associated with acute renal failure; the mechanism and the underlying renal injury are not completely understood. We report what is, to our knowledge, the first renal biopsy in this context. A 56-year-old patient underwent 2 consecutive vascular imaging procedures in conjunction with gadolinium-based contrast medium administration. A few days later, the patient developed acute renal failure. A renal biopsy showed acute tubular cell injury including patchy tubular cell necrosis, tubular cell degeneration, and marked proliferation of tubular cells, together with mild interstitial edema and interstitial inflammation, but without significant glomerular or vascular changes. During supportive therapy, renal function was partially regained. This case emphasizes the potential nephrotoxicity of gadolinium-based contrast media and suggests that the nephrotoxicity is related to potentially reversible acute tubular cell injury.

Lead arthritis and lead poisoning following bullet wounds: A clinicopathologic, ultrastructural, and microanalytic study of two cases

Bullet wounds causing lead synovitis in the wrist and knee are reported in two patients, one of whom also developed clinical plumbism. Very high lead levels in the synovial fluid are believed to be responsible for toxicity changes that occurred in the synovium and bone. Ultrastructurally, these alterations included the formation of nuclear lead inclusions, dilation, and degranulation of the rough endoplasmic reticulum and deposition of crystalline precipitates in the matrix of the mitochondria in macrophages, osteoclasts, and synoviocytes, as well as the development of cytoplasmic lead inclusions in osteoclasts. Energy-dispersive x-ray elemental analysis (EDXEA) indicated that the nuclear inclusions contained only lead, whereas precipitates within the mitochondria and elsewhere in the cytoplasm were composed of complexes containing lead, calcium, and phosphorus. Similarly constituted extracellular complexes were incorporated into newly formed trabecular bone laid down as a physiologic response to the bullet lodged within the wrist bones. This bone subsequently exhibited defects in bone resorption, which were characterized by depressed osteoclastic function and a unique lesion termed incomplete osteocytic osteolysis. The genesis of this latter lesion is uncertain. The sequestration of the partially degraded bone fragments containing lead complexes into the marrow and eventually into the joint spaces and synovium permitted the recycling of bone lead, and this may have played an important role in inducing clinical plumbism in one of the patients in this study.

Intraluminal crystalloids in prostatic adenocarcinoma immunohistochemical, electron microscopic, and X‐ray microanalytic studies

Histochemical, immunohistochemical, electron microscopic, and x‐ray microanalytic studies were performed on crystalloids within glandular lumina of adenocarcinomas of the prostate. In a review of light microscopic sections of 343 prostatic adenocarcinomas, unequivocal crystalloids were identified in 35 cases (10.2%). Immunohistochemical and ultrastructural studies revealed distinct differences between these crystalloids and the Bence Jones crystals of multiple myeloma: anti‐kappa and anti‐lamda immunostaining was negative, and the characteristic lattice‐like architecture of Bence Jones crystals was not seen. Differences from corpora amylacea also were demonstrated. X‐ray microanalysis did not elucidate the nature of the prostatic crystalloids, and their biochemical composition and mode of formation remain uncertain. Detection of the crystalloids in light microscopic sections nevertheless can aid in the diagnosis of prostatic adenocarcinoma, particularly when the tissue is distorted by crushing artifact, or if the tumor is so well‐differentiated that it can be confused with atypical hyperplasia or inflammatory atypia. When intraluminal crystalloids are detected in prostatic glands that appear histologically benign or atypical, study of additional levels or a repeat biopsy should be undertaken. Cancer 57:2397–2407, 1986.

Distribution of elements in rat peripheral axons and nerve cell bodies determined by X-ray microprobe analysis

Abstract: X‐ray microprobe analysis was used to determine concentrations (millimoles of element per kilogram dry weight) of Na, P, Cl, K, and Ca in cellular compartments of frozen, unfixed sections of rat sciatic and tibial nerves and dorsal root ganglion (DRG). Five compartments were examined in peripheral nerve (axoplasm, mitochondria, my‐elin, extraaxonal space, and Schwann cell cytoplasm), and four were analyzed in DRG nerve cell bodies (cytoplasm, mitochondria, nucleus, and nucleolus). Each morphological compartment exhibited characteristic concentrations of elements. The extraaxonal space contained high concentrations of Na, Cl, and Ca, whereas intraaxonal compartments exhibited lower concentrations of these elements but relatively high K. contents. Nerve axoplasm and axonal mitochondria had similar elemental profiles, and both compartments displayed proximodistal gradients of decreasing levels of K, Cl, and, to some extent, Na. Myelin had a selectively high P concentration with low levels of other elements. The elemental concentrations of Schwann cell cytoplasm and DRG were similar, but both were different from that of axoplasm, in that K and Cl were markedly lower whereas P was higher. DRG cell nuclei contained substantially higher K levels than cytoplasm. The subcellu‐lar distribution of elements was clearly shown by color‐coded images generated by computer‐directed digital x‐ray imaging. The results of this study demonstrate characteristic elemental distributions for each anatomical compartment, which doubtless reflect nerve cell structure and function.

Intraluminal crystalloids in malignant salivary gland tumours

The ultrastructural, X-ray microanalytical, histochemical and immunocytochemical features of intraluminal crystalloids found in adenocarcinomas of the parotid gland have been studied. The crystalloids, putatively derived from an abnormal crystalization of salivary duct proteins, are considerably different from the crystalloids found in normal parotid glands, pleomorphic adenomas, and sialocysts.

Smoke inhalation: An ultrastructural study of reaction to injury in the human alveolar wall

This study was undertaken to determine the site of initial pulmonary injury in smoke inhalation. A hotel fire in Houston, Texas, resulted in the on-site deaths of 10 white people (2 to 62 years of age). All underwent autopsy examinations which included measurement of carbon monoxide (CO) and cyanide (CN) levels, as well as electron microscopy of lung samples. Average CO levels of 40% and CN levels of 0.6 ppm were obtained. In all cases, the lungs were heavy, hyperemic, and edematous with soot staining the tracheobronchial mucosa. Light microscopy showed soot, pulmonary congestion, and edema. Electron microscopy confirmed the presence of interstitial and intraalveolar congestion and edema. Carbon particles were also present, and occasionally were seen undergoing phagocytosis by alveolar macrophages. Intracellular edema with focal bleb and vesicle formation was prominent within Type I pneumocytes in 9 of 10 cases. Endothelial cells showed similar but much less severe changes, lacking the distinct blebs seen in the Type I cells. This investigation reveals that smoke, like ammonia inhalation and nitric acid instillation, appears to cause pulmonary edema by initial injury to the Type I pneumocyte.