Douglas R. Shanklin

Hepatic histopathologic condition does not correlate with laboratory abnormalities in HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count)

OBJECTIVE Our objective was to categorize the histologic findings in the liver in patients with HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count) and to correlate these findings with the severity of clinical laboratory abnormalities. STUDY DESIGN Eleven patients with laboratory criteria for HELLP syndrome who required cesarean delivery underwent needle biopsy of the liver under direct visualization. RESULTS Eight patients had periportal hemorrhage, and six had fibrin deposition. Fatty infiltration was seen in four, one with large-droplet fat, three with microvesicular fat. There was no statistically significant correlation between the severity of the histologic findings of periportal hemorrhage and fibrin deposition and the clinical laboratory findings. Fatty infiltration did not correlate with the severity of the HELLP syndromes histologic condition, but, in contrast, did correlate with thrombocytopenia and aminotransferase elevations. CONCLUSIONS Laboratory abnormalities do not accurately reflect the severity of the underlying histopathologic condition in HELLP syndrome. We propose that all patients with HELLP syndrome, regardless of the degree of their laboratory abnormalities, be treated aggressively, primarily with delivery.

Ultrastructural aspects of preeclampsia: I. Placental bed and uterine boundary vessels

Biopsy specimens were obtained under direct vision at the time of cesarean section from 42 patients (33 preeclamptic and nine normotensive patients) and from three hysterectomies (all in normotensive patients). Mean gestational age was 32.8 +/- 0.9 week (range, 26 to 40 weeks) in women with preeclampsia and 36.1 +/- 1.1 weeks in normotensive women (range, 32 to 41 weeks). Tissues were obtained from the central placental bed and from nonplacental sites. Specimens were examined histologically and by electron microscopy. Ultrastructural changes in small vessels, primarily venules, were compared with preeclamptic blood pressure. Extensive ultrastructural endothelial injury was found consistently in both site and nonsite areas in all of the specimens from women with preeclampsia but not in normotensive women (p less than 0.0001). There was no apparent correlation between the type or degree of endothelial damage and maternal hypertension. The same types and relative severity of specific vascular injury were present in both placental and nonplacental sites. Endothelial and derivative vascular injury occurs more or less uniformly in the uterus in preeclampsia, especially along the boundary zone between maternal and fetal tissues.

The immunopathology of siliconosis. History, clinical presentation, and relation to silicosis and the chemistry of silicon and silicone.

Recent evidence confirms the fundamental involvement of the human immune system in the reaction to implantation of siliconebased medical devices. An as yet-to-be particularized epitope of many complex substances sharing siloxane structures is presented through the MHC-II apparatus with development and retention of T cell memory. This memory can be tested for in practical terms using one or more forms of silica, which links the immunohistopathology and autoimmune attributes of “silicosis” with those of “siliconosis.” The lesions of siliconosis are typical of those for persistent antigens and delayed, cell mediated hypersensitivity. The basic descriptive pathology of the reaction to silicone has been known since soon after introduction of silicones in medical procedures, with the exception of some details related to the more recent discoveries on the role of cytokines in the immunopathic process. The clinical consequences of siliconosis are common and can be severe in some individuals implanted with silicone devices.

Thyroid Hormone Control of Brain and Motor Development: Molecular, Neuroanatomical, and Behavioral Studies

Thyroid hormones, T3 and T4, have been shown to play significant but poorly understood roles in development and differentiation of rodent and human brain(Lauder, 1989; Legrand, 1982–83; Stein et al, 1989a; 1991a,d; Eayrs, 1968; Morreale de Escobar et al, 1984; Garza et al, 1988; Ruiz-Marcos, 1989; Nunez et al, 1989). Hypothyroidism leads to molecular(Stein et al, 1989a,c; 1991a; Nunez et al, 1989; Hendrich et al, 1987), neuroendocrinological(Noguchi et al, 1986, Bakke et al, 1975, Stein et al, 1989b, Porterfield et al, 1981), neuroanatomical(Lauder et al, 1986; Lauder, 1989; Ruiz-Marcos, 1989; Eayrs, 1955; Garza et al, 1988; Morreale de Escobar et al, 1989; Marc et al, 1985; Legrand, 1982–83; Rami et al, 1986b; Narayanan et al, 1985; Marinesco, 1924; Lotmar, 1928; Rosman, 1975), behavioral and neuropsychological(Adams et al, 1989,1991; Anthony et al, 1991; Eayrs, 1968; Davenport et al, 1976; Klein, 1985; Rovet et al, 1987; Rovet, 1989; Man, 1971; Boyages et al, 1988; Pharoah,1984), and neurological abnormalities(Chaouki et al, 1989; Boyages et al, 1988; Delong et al, 1985; Nelson et al, 1986; Macfaul et al; 1978; Stein et al, 1991d, Rochiccioli et al, 1989) in the developing brain. Specifically, disorders of neuronal process growth and connectivity are noted neuroanatomically and motor syndromes involving motor cortex and pyramidal tracts are commonly observed in hypothyroid humans and rodents. These neurological and neuropathological abnormalities may be predicated on abnormalities in the cytoskeletal structures and in their molecular components. The cytoskeleton is a primary target for thyroid hormone in euthyroid and hypothyroid brain.

Recurrent acute fatty liver of pregnancy

The first reported case of recurrent acute fatty liver of pregnancy confirmed by biopsy is described. In this case a high index of suspicion led to an early diagnosis and intervention with resultant improved maternal and fetal outcome. Electron microscopic examination of a liver biopsy specimen proved more beneficial in confirmation of the diagnosis compared with routine microscopic examination.

Monocyte-Dependent Stimulation of Human T Cells by Silicon Dioxide

Mononuclear cells were isolated by Ficoll-Hypaque density gradient centrifugation from randomly selected silicone breast implant recipients for testing. Restricted antibody to HLA-DR (28–33 kD) depleted the concanavalin A mitogenic response which was expected but failed to inhibit the proliferative response to silicon dioxide. Further testing with monoclonal antibodies to HLA-DP, -DQ, and a second -DR with specificity for the NS1 region of the MHC class II genome, all markedly inhibited proliferation of T cells despite otherwise adequate stimulation by concanavalin A or silicon dioxide. Monoclonal antibodies directed against B7-1 also inhibited proliferation of T cells following stimulation with concanavalin A or silicon dioxide. These results confirm the T-cell response to silicon dioxide is monocyte-dependent and not a superantigen as has been speculated.

LYMPHOCYTE RESPONSE TO SILICA AMONG OFFSPRING OF SILICONE BREAST IMPLANT RECIPIENTS

The current study evaluated immune response to silicon dioxide in children born to women with silicone breast implants. In part one of the study, the T lymphocytes of 21 of 24 such children were significantly stimulated by silicon dioxide (silica). Part two consisted of eleven children, four born preimplantation and seven born postimplantation. None of the preimplant offspring showed T cell responses to silica; five of the seven postimplant children were positive for T cell memory for silica. Part three was a blinded study based on statistically significant differences in T cell stimulation with silicon dioxide between postimplant children and controls. These findings indicate a common immune reaction, that of T cell memory, occurs in mothers and their children born after exposure to silicone mammary implants placed prior to pregnancy. Since not all such children were breast fed the result favors transplacental passage of immunogens such as silicone oligomers or through maternofetal cellular traffic.

Pathologic studies of fetal thyroid development.

Ordinarily the assignment of tissue change to the category of lesion or to variation is straightforward, depending on the character and extent of the change and its functional impact. The developmental process alters this relationship in large part because the effect is often in the future, sometimes the distant future. As such, what is “pathological” from the developmental point of view requires more understanding of the coordination of developing systems, the sequences for obtaining functional competency, and the effects of growth, maturation, and diseases in other organ systems. Specified injuries may have different effects on the time scale of development. Moreover, lesions in fetuses and newborns often have unusual features. It should be kept in mind that much of the final form, content, and location of many organs often depends on the removal of primordial structures which were earlier stages of those tissues. For the thyroid gland the process in question is that of folliculogenesis [Norris, 1914]. through the formation of a primordium later converted to follicles, a unique vertebrate structure.