Search

Toxic epidermal necrolysis (TEN) is a severe cutaneous reaction that most commonly is related to drug exposure and that clinically can be confused with other bullous dermatoses, particularly staphylococcal scalded skin syndrome (SSSS) and erythema multiforme major (the Stevens-Johnson syndrome). We report the first case, to our knowledge, of TEN associated with ethambutol hydrochloride administration. Toxic epidermal necrolysis can be partially differentiated from other bullous dermatoses by history and clinical presentation. Microbiological results (eg, the isolation of Staphylococcus aureus in SSSS) and immunological studies (eg, the demonstration of immune complexes in the Stevens-Johnson syndrome) may aid in differentiation, but ultimately the diagnosis depends on histopathological examination of involved skin.

Detection of gastrointestinal bleeding using Tc-99m labeled RBCs has proven to be clinically useful although false-positive images associated with abnormal vascularity remain problematic. The scintigraphic appearance of a large mesenteric varix is presented, and its potential confusion with gastrointestinal bleeding is discussed. Correlative CT and angiographic images are presented.

Rats injected with bleomycin over a 58-week period developed weight loss, alopecia, hyperpigmentation, skin thickening and skin tautness when compared with saline-injected control animals. The only significant abnormality in laboratory blood tests was an increased sedimentation rate in the bleomycin-treated rats compared with controls. Histological examination of dorsal skin showed atrophied sebaceous glands and increased collagen fibres, with diameters ranging from 37.5 to 75 nm as compared with 72.5 to 100 nm in control animals. Chronic bleomycin exposure produces clinical, histological and ultrastructural skin changes similar to those found in human progressive systemic sclerosis (scleroderma).

The ability to accurately distinguish remaining or recurrent high-grade astrocytoma from necrosis or edema following treatment is essential to optimal patient management. Thallium 201 planar gamma-camera imaging has been shown to be helpful in detecting recurrent high-grade astrocytoma; however, due to tissue heterogeneity adjacent to and within tumor, the cellular specificity and quantification of 201Tl uptake are largely unknown. In order to determine which tissues are responsible for the radioisotope uptake, microautoradiographic techniques were used to examine multiple tissue sections from five patients with high-grade astrocytoma. Each patient received 5 mCi of 201Tl i.v. 1 h prior to tumor removal. Additionally, all patients received computerized tomographic and 201Tl planar gamma-camera scans prior to surgery. Following surgery, the excised tissue specimens were tentatively classified by gross pathological examination and then immediately processed for dry mount autoradiography; grain density was determined over regions containing tumor, adjacent and uninvolved brain tissue, necrotic tissue, and background. Highly significant differences were found in grain densities (201Tl uptake) between tumor and uninvolved brain tissue, as well as between uninvolved brain tissue and necrotic tissue; there was no significant difference between background grain density and that in necrotic tissue. Mean grain densities (grains/cm2 +/- 1 SD) across patients were: tumor, 102 +/- 23; adjacent, uninvolved brain tissue, 29 +/- 11; necrotic tissue, 6.2 +/- 1.1; and background, 7.0 +/- 4.1. We conclude that the ability of 201Tl to selectively image high-grade astrocytoma is due to its preferential uptake into tumor cells.

A human fetal liver cDNA library was screened at reduced hybridization stringency for v-raf-related sequences. In addition to the expected c-raf-1 cDNA, a second sequence was isolated. Comparison of the second gene (pks) to the other raf-related sequences revealed nucleotide homologies of 71%. The predicted amino acid sequence of the kinase domain is sufficiently similar to that of v-raf to suggest that pks may encode a polypeptide that exhibits serine/threonine kinase activity. The expression of pks mRNA (2.7 kilobases long) is elevated in peripheral blood mononuclear cells isolated from two patients with angioimmunoblastic lymphadenopathy with dysproteinemia, a disease in which autoantibodies are produced following the lymphoproliferative activation of B cells. Analysis of somatic cell hybrids for segregation of the pks locus revealed the presence of an additional locus closely related to the pks sequence.

The correlation of anatomical with functional brain images is of critical importance for data analysis. We have designed and tested a reference system method that provides accurate localization of neuroanatomy on functional brain images. The method differs from prior techniques using headholding devices in that it does not require head fixation and is noninvasive. The reference system can be quickly, accurately, and reproducibly applied to the patient's head with respect to the surface anatomy of the head. The reference system is easily adaptable to multiple imaging modalities. The reference system is implemented with the aid of a computer algorithm that reconstructs the anatomic images into a new image matching a selected functional image. Accuracy and reproducibility of placement of the reference system was demonstrated by the application of the system on multiple subjects by two independent observers. The use of this method provides accurate correlation between functional and anatomical brain images.

Mice and humans with systemic lupus erythematosus (SLE) have been studied with regard to cellular, genetic and molecular genetic abnormalities. B cell hyperactivity and autoantibody production are the hallmarks of this illness. In humans with SLE, there is increased stem cell, B cell precursor and B cell proliferation. The same is true of NZB mice. In lpr/lpr and gld/gld mice, marked expansion of a subpopulation of T cells allows extrathymic terminal T cell maturation and secondary B cell hyperactivity. Androgens suppress these processes and polyclonal immune activators accelerate them. Three types of genes are identified: inducing genes, accelerating genes and background genes. These give rise to abnormal expression of various cellular oncogenes, T cell receptor genes and immunoglobulin genes. The data suggest that abnormal immune regulation plays a critical role in the development of SLE, with polyclonal B cell activation being common to both mice and humans with SLE. Different genetic and cellular abnormalities underlie the ultimate syndrome, the common denominator, generalized autoimmunity, that we call SLE.

This article is intended to elucidate some of the neuropathogenetic mechanisms possibly operative in obsessive-compulsive disorder (OCD). Relevant literature is reviewed, with attention to psychologic, and pathologic considerations. Anatomy, neurochemistry, and known functional associations with neuropathological and behavioral abnormalities of implicated brain regions are discussed. The authors propose that dysfunction of neuronal circuits interconnecting the orbitofrontal cortex, basal ganglia/limbic striatum, and thalamus serves a critical role in the pathogenesis of OCD and that obsessive-compulsive symptoms occur when an aberrant positive feedback loop develops in the reciprocally excitatory frontothalamic neuronal interchange, which is inadequately integrated or inhibited by the ventromedial (limbic) portions of the striatum; the ventromedial striatum may serve to modulate activity in the frontothalamic circuit through a negative feedback loop.

A single recessive gene, lpr, induces an autoimmune-lymphoproliferative syndrome in several strains of mice. The lymphoid organs of lpr/lpr mice contained cells with increased amounts of myb RNA, which codes for a protein found in the nucleus. A similar human lymphoproliferative disorder also had an increase in c-myb expression. Mouse T cells induced by mitogens to proliferate did not express large amounts of myb RNA, indicating that marked myb expression is not a general feature of lymphocyte activation and proliferation.

Systemic autoimmune disease states are known to be associated with abnormal cell growth or differentiation. In the murine models of systemic lupus erythematosus (SLE), specific genotypes result in dysregulated growth of certain lymphocyte subpopulations. Although genes underlying autoimmune syndromes have been characterized by mendelian genetics, it has not yet been possible to characterize them at the molecular level. Recently, it has become clear that cellular proto-oncogenes can regulate cell growth and differentiation. Therefore, we have studied the expression of five different proto-oncogenes; myc, myb, abl, bas, and raf, in organs and cells of various autoimmune strains. These genes were selected because each has previously been associated with abnormal hemopoietic cell growth, and because each has been at least partially characterized at the molecular and functional level. We have found selective abnormal proto-oncogene expression associated with the characteristic abnormal cell growth or differentiation of lymphocytes of autoimmune mice. The lymph nodes of MRL-lpr/lpr mice are packed with unusual T cells. These had a marked increase in myb expression. There was a 20-40-fold increase in myb RNA in lymph nodes of lpr/lpr mice on several different genetic backgrounds. The gld/gld mouse has a very similar unusual T cell in the lymph nodes: it also had a comparable increase in myb RNA in the nodes. In contrast, myb expression was not elevated in the other autoimmune mouse strains lacking these abnormal T cells. Whereas such lpr/lpr mice had increased myb expression in the lymph nodes and splenic T cells, they had markedly subnormal myb expression in the thymus, an organ with high myb in normal and in the other autoimmune strains. These results suggest that one phase of intrathymic differentiation in other mice occurs in the periphery of lpr/lpr mice. The spleens of NZB and male BXSB mice had increased myc expression which was found to be associated with B cells upon cell separation. Similarly, increased bas and abl expression was associated with autoimmune B cells. The xid gene, which retards or prevents the expression of murine lupus by retarding B cell maturation, was associated in BXSB.xid, NZB.xid, and MRL-lpr/lpr.xid congenic mice with marked reduction in expression of myc, bas, and abl in the spleens containing B cells, but not of myb in the lpr/lpr.xid nodes containing primarily the unusual T cells. Raf expression was found to be associated in lpr/lpr and gld/gld mice with both the unusual T cells and splenic B cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Treatment of high-grade astrocytoma includes surgery, chemotherapy, and various methods of irradiation. Radiation therapy usually results in necrosis and edema around the primary tumor site. Contrast-enhanced computerized tomography (CT) and standard radionuclide imaging techniques are unable to reliably distinguish recurrent tumor from necrosis or edema since these images depict localization of contrast material or tracer, which primarily depends on blood-brain barrier breakdown. Thallium-201 (201Tl) appears to incorporate into viable tumor cells more rapidly than into normal brain cells. This report describes a new method to quantify the uptake of 201T1 in the tumor: the tumor-to-cardiac uptake ratio (T/C). Twenty-three 201T1 brain scans were performed on eight patients to differentiate recurrent viable high-grade astrocytoma from posttherapy changes. Planar images of the head and heart were obtained in order to calculate the ratio of tumor counts to cardiac counts. This ratio represents a numerical estimation of 201T1 uptake in the brain tumor relative to cardiac counts and is expressed as the T/C index. The T/C index correlated well with the clinical course in all eight patients. In general, however, CT suggested more extensive regrowth of tumor than the actual clinical status suggested. In one patient's course of radiological monitoring, tumor recurrence was detected by means of 201T1 imaging four months prior to its appearance on CT. In conclusion, when performed serially, the T/C index can provide an accurate estimate of residual tumor burden or recurrence, and detect and quantify viable tumor during therapy.

Regional cerebellar perfusion was imaged using technetium Tc 99m hexamethylpropylene amine oxime and single photon emission computed tomography (HM-PAO-SPECT) in a patient with chronic left lateral medullary syndrome with contralateral weakness due to traumatically induced thrombosis of the left vertebral artery. Despite continued neurologic deficits, x-ray transmission computed tomography was normal. However, HM-PAO-SPECT demonstrated that blood flow to the left cerebellar hemisphere was significantly impaired. This abnormality was still apparent after correction for atrophy as estimated by magnetic resonance imaging. Technetium Tc 99m hexamethyl-propyleneamine oxime and single photon emission computed tomography effectively imaged regional blood flow in the vertebrobasilar circulation and appears to more clearly reflect the nature and extent of the neurologic deficit than either x-ray transmission computed tomography or magnetic resonance scanning.

Bone imaging of the body is often requested to rule out metastatic disease. A patient with suspected breast carcinoma underwent bone imaging which revealed a focal area of uptake that appeared to be localized in the right posterior calvarium. The initial interpretation was possible solitary metastatic breast carcinoma to the skull. Skull radiographs and head computed tomography (CT) were suggested for follow-up evaluation. The skull series was performed immediately after bone imaging and was negative. Further clinical information revealed that the patient recently had undergone total right internal carotid artery ligation for treatment of a large, surgically inaccessible right cavernous aneurysm. SPECT imaging of the head localized the region of abnormal uptake adjacent to the calvarium, which suggested the uptake was due to a recent brain infarction or metastatic disease to the brain. A CT scan performed 4 days later demonstrated generalized cerebral atrophy, but was otherwise normal, ruling out metastatic breast carcinoma. This case emphasizes the importance of SPECT imaging when a solitary skull lesion is found on bone imaging. SPECT can localize the lesion to be within the brain and/or skull and can aid in further investigative management. A lesion located at the periphery of the brain may be due to an occult stroke. This finding is of particular consideration in the elderly in whom there is a relatively high incidence of coexisting cancer and silent brain infarction.

To assess the potential role of scintigraphy in the evaluation of clinically and biochemically suspect ovarian hyperandrogenism (HA), dexamethasone suppression 131I-6 beta-iodomethyl-19-norcholesterol (NP-59) scans were performed to characterize ovarian function in nine patients. Pelvic ultrasound and/or computed tomography (CT) identified anatomic abnormalities in the adnexal region in six women in whom there was discernible pelvic accumulation(s) of NP-59. In the remaining three patients testosterone levels were normal or only slightly elevated and the NP-59 scan did not demonstrate abnormal adrenal or pelvic uptake. CT and/or ultrasound studies failed to demonstrate an abnormality in the pelvis suggesting excessive peripheral conversion or abnormal end organ sensitivity of androgen precursors as potential etiologies of their HA. In three women with androgen secreting lipoid tumors of the ovary, unilateral, pelvic NP-59 activity was noted; these tumors were subsequently resected. Two women with bilateral pelvic NP-59 uptake were later shown to have hyperthecosis with markedly asymmetric and enlarged ovaries. In one woman the extent of asymmetric NP-59 uptake was anticipated by the asymmetry of ovarian vein androgen levels at selective venous catheterization. In another woman with markedly asymmetric polycystic ovary disease, intense focal uptake of NP-59 localized to the side of the anatomically abnormal, enlarged ovary. Thus, our preliminary study reviews our experience to date and suggests that NP-59 scintigraphy may be used to localize both tumorous and nontumorous ovarian dysfunction in states of HA and virilization.

A prominent filling defect was depicted on a radionuclide ventriculogram in a patient with mitral regurgitation. This defect was later shown, by cardiac ultrasound, to be due to mitral valve prolapse into the left ventricle during diastole. This case illustrates that mitral valve prolapse should be added to the list of clinical entities that can result in an intraventricular defect on a radionuclide ventriculogram.

99mTc-HM-PAO was used to evaluate regional cerebral blood flow in a 26-year-old woman with Moyamoya disease. This patient had an 18-month history of recurrent neurologic deficits and had angiographic evidence of Moyamoya disease. She had used oral contraceptives and cigarettes, but had no other risk factors for stroke. Single photon emission computed tomographic images showed bilateral and asymmetric reductions in blood flow to anterior and lateral brain regions. These findings correlated better with clinical symptomatology and suggested more extensive brain involvement than did computed tomography.