Florabel G. Mullick

Drug related vasculitis: Clinicopathologic correlations in 30 patients*

Drug related vasculitis has variously been described as necrotizing hypersensitivity or allergic angiitis or microscopic panarteritis nodosa. We reviewed tissue sections from 30 patients with validated drug hypersensitivity and vasculitis in order to precisely define this entity. No evidence of necrotizing vascular lesions or of fibrinoid associated with necrosis was found. The vascular lesions in all 30 patients involved small arteries, arterioles, capillaries, and venules. The inflammatory infiltrate consisted primarily of mononuclear cells and prominent numbers of eosinophils and was present in all three layers of the involved vessel walls. Clinically the patients developed either localized or systemic vasculitis, which could not be predicted on the basis of the associated drug. The findings of a skin rash, fever, or eosinophilia and the development of symptoms consistent with a hypersensitivity reaction while medication was being taken were all suggestive of the diagnosis of drug related vasculitis.

Drug related myocarditis: I. Hypersensitivity myocarditis

The purpose of this study was to characterize in detail the morphologic changes in one form of drug related myocarditis: hypersensitivity myocarditis. We reviewed the clinical histories and microscopic findings in 24 patients with validated drug hypersensitivity and myocarditis. The myocarditis in these patients was characterized by a patchy interstitial inflammatory infiltrate rich in eosinophils, focal myocytolysis, prominent perivascular infiltrates, an absence of myocardial fibrosis, and the uniform features of the myocarditis in each patient. Twenty of the 24 patients died suddenly and unexpectedly. In retrospect, the presence of signs and symptoms of hypersensitivity (skin rash, fever, eosinophilia, and malaise) and nonspecific cardiac findings (electrocardiographic changes, tachycardia, or serum enzyme elevations) were suggestive of hypersensitivity myocarditis in these patients. Since early diagnosis is vital in hypersensitivity myocarditis, the presence of nonspecific cardiac findings in a patient receiving any drug associated with hypersensitivity should alert the clinician to the possibility of drug related myocarditis.

Detection of titanium in human tissues after craniofacial surgery.

&NA; Generally, titanium fixation plates are not removed after osteosynthesis, because they have high biocompatability and high corrosion resistance characteristics. Experiments with laboratory animals, and limited studies of analyses of human tissues, have reported evidence of titanium release into local and distant tissues. This study summarizes our results of the analysis of soft tissues for titanium in four patients with titanium microfixation plates. Energy dispersive x‐ray analysis, scanning electron microscopy, and electrothermal atomic absorption spectrophotometry were used to detect trace amounts of titanium in surrounding soft tissues. A single metal inclusion was detected by scanning electron microscopy and energy dispersive x‐ray analysis in one patient, whereas, electrothermal atomic absorption spectrophotometry analyses revealed titanium present in three of four specimens in levels ranging from 7.92 to 31.8 &mgr;g/gm of dry tissue. Results from this study revealed trace amounts of titanium in tissues surrounding craniofacial plates. At the atomic level, electrothermal atomic absorption spectrophotometry appears to be a sensitive tool to quantitatively detect ultra‐trace amounts of metal in human tissue.

Enflurane Hepatotoxicity: A Clinicopathologic Study of 24 Cases

Analysis of 24 cases of enflurane anesthesia-associated hepatic injury shows that the clinical, biochemical, and histologic features are similar to those seen with halothane- and methoxyflurane-related hepatitis. Postoperative fever was the presenting symptom in 19 patients. Jaundice occurred in 19 patients after a mean latent period of 8 days. Sixteen patients had been previously exposed to enflurane or halothane, and the latent period from exposure to the onset of symptoms or jaundice was shortened in these patients. There were five fatalities among the entire group. Liver biopsy most characteristically showed centrilobular necrosis, occasionally with ballooning degeneration and fatty change. The presumed mechanism of injury is metabolic idiosyncracy, and prior exposure to a haloalkane anesthetic may increase the risk of hepatic injury after enflurane administration.

Pemoline-associated hepatic injury

Among 100 cases of hepatic injury attributed to the administration of pemoline, 43 had sufficient accompanying information to permit analysis. All but two patients were less than 20 years old, and 80% were less than 12 years old. Males predominated the study. Injury appeared as early as 1 week or as late as greater than 1 year of taking the drug. The injury was uniformly hepatocellular as judged by the high values for aminotransferases and by death in massive necrosis in one patient. Mechanism was judged to be idiosyncratic, and the idiosyncrasy was probably metabolic rather than immunologic.

Identification of titanium in human tissues: probable role in pathologic processes.

Six cases of titanium dioxide exposure involving lung, skin, and synovium are described, with a review of the literature. The patients, four men and two women, were between the ages of 22 and 65 years. The pulmonary changes were characterized by fibrosis and numerous macrophages with abundant deposition of a black pigment. Adjacent areas of bronchopneumonia were also observed. In the skin a severe necrotizing lesion involving the subcutaneous tissue with extension to the muscle was observed in one case and a nonspecific inflammatory response was observed in another; both cases showed abundant black pigment deposition. Electron microscopy and energy dispersive x-ray analysis demonstrated the presence of large quantities of titanium in the pigment granules. There may be a combination of black pigment deposition and fibrosis, necrosis, or a xanthomatous or granulomatous reaction, that, together with negative results on special staining and culture studies for organisms, should raise the suspicion of titanium-associated injury and prompt the study of the affected tissues by x-ray analysis for positive identification.

A clinical and pathological comparison of the WHO and CDC case definitions for AIDS in Kinshasa, Zaïre: is passive surveillance valid?

Objectives:To compare the specificity of the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) case definitions for AIDS in autopsy cases from Zaïre. Setting:Mama Yemo Hospital and University Hospital morgues in Kinshasa, and Karawa Hospital in Equateur Region, Zaïre. Methods:Autopsy cases with a clinical diagnosis of AIDS on the death certificate or chart were studied. Evaluation included post-mortem HIV-1 serology, chart review for specific AIDS-related symptoms and signs, and application of WHO and CDC case criteria to the clinical and autopsy diagnoses. Results:Of the 68 diagnosed AIDS cases, 98% fulfilled WHO criteria for AIDS and 93% fulfilled both WHO and CDC criteria. All cases fulfilling both criteria were HIV-1-seropositive. Opportunistic infections accounted for 84% of CDC AIDS-defining conditions. Disseminated tuberculosis was the most frequent (41%) specific diagnosis; Pneumocystis carinii pneumonia was rare (<2%). Conclusions:There was good concordance between WHO and CDC case definitions. A diagnosis of AIDS on the chart or death certificate is adequate for surveillance purposes in this population.

Nodular Regenerative Hyperplasia of the Liver in Children

Sixteen cases of nodular regenerative hyperplasia of the liver in children are presented. The patients, 10 girls and 6 boys, were between the ages of 7 months and 13 years, with a median of 6 years. Clinically, nine children presented with hepatomegaly or splenomegaly, with and without signs of portal hypertension. A history of anticonvulsant drug therapy was obtained in four patients. Associated conditions in the remaining three cases were Donohues syndrome, disseminated intravascular coagulation, and angiomyolipoma of the kidney. In five patients a clinical diagnosis of primary intra-abdominal tumor was made. Follow-up showed that six patients died of causes unrelated to the nodular hyperplasia. Two patients were asymptomatic when last seen 5 and 18 years after the initial diagnosis of nodular hyperplasia. Both patients underwent shunt surgery. No follow-up was available for eight patients. The importance of recognizing this entity in the pediatric age group, as well as its histopathologic differential diagnosis, is stressed.

Pathology of lymph nodes From patients with breast implants : A histologic and spectroscopic evaluation

There are only a few published reports describing the pathology of regional lymph nodes from patients with silicone breast implants. Systematic analytical chemical verification of foreign material has not previously been reported. In this study, biopsies of regional lymph nodes from 96 patients with breast implants were studied using conventional histology as well as laser-Raman microprobe spectroscopy and Fourier transform infrared microspectroscopy. Lymph nodes from 12 patients without implants served as negative controls. Foamy macrophages, ranging from rare scattered cells to confluent sheets, were observed in sections of lymph nodes from 91 patients with implants and only rare foamy macrophages were observed in sections from 4 patients without implants. Refractile material consistent with silicone was observed in sections from 86 patients with implants and in no sections from patients without implants. Fragments of foreign material consistent with polyurethane were observed in sections from 16 patients with implants and in no sections from patients without implants. Using spectroscopy, the presence of silicone was confirmed in 71 patients with implants, and the presence of polyurethane was confirmed in 2 patients with implants. Spectroscopy was negative for silicone and polyurethane in all patients without implants. In summary, regional lymph nodes from patients with breast implants often have histologic evidence of silicone migration. Characteristic histologic findings include foamy macrophages and refractile droplets of clear material. Polygonal fragments of polyurethane were observed in lymph nodes from a number of patients. This finding has not been previously reported. The presence of silicone and polyurethane was confirmed using confocal laser-Raman microprobe and Fourier transform infrared microspectroscopy. Other than two prior case reports, this is the first confirmatory evidence of silicone migration to lymph nodes in patients with breast implants and this is the first confirmatory report of polyurethane migration to lymph nodes.

Presence and localization of three lactic acid transporters (MCT1, -2, and -4) in separated human granulocytes, lymphocytes, and monocytes.

We fractionated leukocytes from three donors into >90% pure samples of granulocytes, lymphocytes, and monocytes and tested them for transcriptional and translational expression of three physiologically-proven lactate transporters, monocarboxylate transporter 1(MCT1), MCT2, and MCT4, using RT-PCR and affinity-purified rabbit antibody (Ab) to the C-terminal segment of each human MCT. Transcripts of all three MCTs were identified in each leukocyte fraction by RT-PCR and proven by sequencing of fragments extracted after isolation on agarose gels. Transporter protein of the appropriate size was demonstrated for each of the monocarboxylate transporters MCTs in lymphocytes and monocytes by Western blot, while lower-molecular-weight bands were found in granulocytes and are presumed to be degraded forms, because they were blocked by antibody-antigen (Ab-Ag) preincubation. IHC demonstrated all three MCTs in methanol-fixed droplets of all three leukocyte fractions; stain was abolished on omission of the primary Ab. Plasmalemmal staining occurred with all MCTs in all leukocyte fractions. Because the Km for lactate increases approximately fivefold at each step, with MCT2<1<4, leukocytes must use the full range of lactate binding to survive in acidic and hypoxic environments. Except for MCT4 in lymphocytes, all the MCTs also stained leukocyte cytoplasm, often with distinct granularity. Nuclear membrane staining was also seen with MCT1 and MCT2, while platelet plasmalemma stained only with MCT2.