[Analysis of the statistical value of various commercially available stool tests - a comparison of one stool sample in correlation to colonoscopy]. / Evaluierung der statistischen Kennwerte verschiedener kommerziell erhältlicher Stuhltests - Ein Quervergleich aus derselben Stuhlprobe in Korrelation zur Koloskopie.

INTRODUCTION: Guajac based fecal occult blood tests have proven to reduce mortality of colorectal cancer - despite their unsatisfactory statistical values. The potential of newer tests is yet inconclusive. We compared two guajac based, four immunochemical and the M2-PK test with colonoscopic and histological results as a reference. METHODS: In 1128 stool samples of patients undergoing (screening) colonoscopy the mentioned tests were performed. RESULTS: Positivity rate was 1.9 to 4.1 % for guajac based and immunochemical tests, M2-PK reached 11.6 %. In case of advanced neoplasias, no significant differences in sensitivity (7.3 - 20 %), specifity (96.6 - 98.4 %), positive predictive value (16.7 - 30.6 %) or accuracy (92.9 - 94.0 %) between guajac based and immunochemical tests were encountered. The slightly higher sensitivity of M2-PK (27.3 %) did not reach statistical significance - however the comparatively low specifity (89.2 %) and accuracy (86.2 %) were clearly lower compared to all other tests. Regarding all neoplasia, immunochemical tests performed better than conventional hemoccult, but the difference did not reach statistical significance. In this group, the sensitivity of M2-PK is clearly better, but specifity is clearly inferior to all other tests. DISCUSSION: Low sensitivity and low predictive values are explained by the study design with single test and low prevalence of neoplasia. Due to small numbers, there is only a trend, but no significant difference between the performance of conventional hemoccult compared with immunochemical and high senstitive guajac tests. Because of its low specificity, M2-PK is not an appropriate screening test for colorectal neoplasia.

The reelin pathway components disabled-1 and p35 in gangliogliomas--a mutation and expression analysis.

Focal epilepsies in young patients are frequently associated with differentiated glioneuronal tumours. Dysplastic neurones represent a characteristic neuropathological feature of gangliogliomas, the most common entity encountered in this group. Here, we have analysed two major components of the reelin pathway involved in neuronal migration and cortical development, that is, p35 and disabled-1 (dab1), in gangliogliomas. Genomic structures of human dab1 and p35 were identified 'in silico' using the HTGS databank, NCBI BLAST 2.1. DNA sequence analysis was carried out in gangliogliomas obtained from 29 epilepsy patients vs. peripheral blood DNA from non-affected control individuals (n = 100). Gene expression of dab1 and p35 was determined by real-time RT-PCR (reverse transcriptase polymerase chain reaction) in gangliogliomas (n = 14) vs. non-neoplastic central nervous system tissue (n = 20). The human dab1 gene contains 13 coding exons and is located on chromosome 1p31-32. A single coding exon constitutes the human p35 gene, which is located on chromosome 17q11.2. A novel homologueous genomic region on chromosome 2 has to be taken into account for future studies on p35. One ganglioglioma patient showed a unique polymorphism in the p35 gene. The single base exchange (C to A) at nucleotide 904 of the p35 cDNA (GenBank X80343, start ATG, codon 302) results in a leucine-isoleucine amino acid substitution. No mutations of the dab1 and p35 genes in gangliogliomas were observed. However, significantly lower levels of dab1 and p35 gene transcripts were detected in gangliogliomas compared to controls (dab1 28.24%, t-test P < 0.001; p35 21.28%, t-test P < 0.001, in gangliogliomas vs. controls). Our data suggest that mutational events of dab1 and p35 are not involved in the molecular pathogenesis of gangliogliomas. A potential functional role of these developmentally regulated genes for the formation of epileptogenic glioneuronal lesions remains to be elucidated.

Distinct expression pattern of microtubule-associated protein-2 in human oligodendrogliomas and glial precursor cells.

Microtubule-associated protein 2 (MAP2), a protein linked to the neuronal cytoskeleton in the mature central nervous system (CNS), has recently been identified in glial precursors indicating a potential role during glial development. In the present study, we systematically analyzed the expression of MAP2 in a series of 237 human neuroepithelial tumors including paraffin-embedded specimens and tumor tissue microarrays from oligodendrogliomas, mixed gliomas, astrocytomas, glioblastomas, ependymomas, as well as dysembryoplastic neuroepithelial tumors (DNT), and central neurocytomas. In addition, MAP2-immunoreactive precursor cells were studied in the developing human brain. Three monoclonal antibodies generated against MAP2A-B or MAP2A-D isoforms were used. Variable immunoreactivity for MAP2 could be observed in all gliomas with the exception of ependymomas. Oligodendrogliomas exhibited a consistently strong and distinct pattern of expression characterized by perinuclear cytoplasmic staining without significant process labeling. Tumor cells with immunoreactive bi- or multi-polar processes were mostly encountered in astroglial neoplasms, whereas the small cell component in neurocytomas and DNT was not labeled. These features render MAP2 immunoreactivity a helpful diagnostic tool for the distinction of oligodendrogliomas and other neuroepithelial neoplasms. RT-PCR, Western blot analysis, and in situ hybridization confirmed the expression of MAP2A-C (including the novel MAP2+ 13 transcript) in both oligodendrogliomas and astrocytomas. Double fluorescent laser scanning microscopy showed that GFAP and MAP2 labeled different tumor cell populations. In embryonic human brains, MAP2-immunoreactive glial precursor cells were identified within the subventricular or intermediate zones. These precursors exhibit morphology closely resembling the immunolabeled neoplastic cells observed in glial tumors. Our findings demonstrate MAP2 expression in astrocytic and oligodendroglial neoplasms. The distinct pattern of immunoreactivity in oligodendrogliomas may be useful as a diagnostic tool. Since MAP2 expression occurs transiently in migrating immature glial cells, our findings are in line with an assumed origin of diffuse gliomas from glial precursors.

Mutational analysis of TSC1 and TSC2 genes in gangliogliomas.

Gangliogliomas constitute the most frequent tumour entity in patients with temporal lobe epilepsy. The characteristic histopathological admixture of glial and neuronal elements, the focal nature and their differentiated phenotype and benign biological behaviour suggest an origin from a developmentally compromised or dysplastic precursor lesion. The present study analysed TSC1 and TSC2 genes as potential candidates involved in the pathogenesis of this intriguing neoplasm. Recent data suggest that both genes play a role in cortical differentiation and growth control. DNA sequence analysis of TSC1 and TSC2 was studied in 20 patients with gangliogliomas. Fifteen of these tumours (75%) carried polymorphisms in the TSC2 gene. The frequency of these polymorphisms was significantly increased in intron 4 (12.5%) and exon 41 (15%) compared to control individuals (8.1 and 6.5%, respectively, n = 100). A somatic mutation in intron 32 of the TSC2 gene was encountered in one patient. In the TSC1 gene, seven polymorphisms occurred as a combination of base exchanges in exon 14 and intron 13. No mutations were observed in this gene. Laser microdissection and harvesting of individual neuronal and glial elements identified the intron 32 mutation within the glial portion but not in dysplastic neurones of the tumour. The data demonstrate numerous polymorphisms as well as a novel TSC2 mutation in gangliogliomas from patients with chronic epilepsies. The selective detection of the TSC2 mutation within the glial component of a ganglioglioma suggests that the glioma portion has undergone clonal evolution in this case.

Increase of nestin-immunoreactive neural precursor cells in the dentate gyrus of pediatric patients with early-onset temporal lobe epilepsy.

A considerable potential for neurogenesis has been identified in the epileptic rat hippocampus. Here, we explore this feature in human patients suffering from chronic mesial temporal lobe epilepsy. Immunohistochemical detection of the neurodevelopmental antigen nestin was used to detect neural precursor cells, and cell-type specific markers were employed to study their histogenetic origin and potential for neuronal or glial differentiation. The ontogenetic regulation of nestin-positive precursors was established in human control brains (week 19 of gestation-15 years of age). A striking increase of nestin-immunoreactive cells within the hilus and dentate gyrus could be observed in a group of young patients with temporal lobe epilepsy (TLE) and surgical treatment before age 2 years compared to adult TLE patients and controls. The cellular morphology and regional distribution closely resembled nestin-immunoreactive granule-cell progenitors transiently expressed during prenatal human hippocampus development. An increased Ki-67 proliferation index and clusters of supragranular nestin-immunoreactive cells within the molecular layer of the dentate gyrus were also noted in the group of young TLE patients. Confocal studies revealed colocalization of nestin and the betaIII isoform of tubulin, indicating a neuronal fate for some of these cells. Vimentin was consistently expressed in nestin-immunoreactive cells, whereas cell lineage-specific markers, i.e., glial fibrillary acidic protein, MAP2, neurofilament protein, NeuN, or calbindin D-28k failed to colocalize. These findings provide evidence for increased neurogenesis in pediatric patients with early onset of temporal lobe epilepsy and/or point towards a delay in hippocampal maturation in a subgroup of patients with TLE.

Endocrine host responses during early and late phases of tumor development.

It is well established that hormones affect tumor growth. Conversely, inoculation of cells obtained from tumors that had been transplanted for many generations causes changes in the concentration of different hormones before and after tumor detection. We aimed at answering the question of whether hormonal alterations also occur during the development of primary tumors and following transplantation of tumors from early generations. Primary tumors were induced in mice by either the carcinogenic agent 3-methylcholanthrene, which produces fibrosarcomas, or the milk-transmitted mammary tumor virus, which induces adenocarcinomas. The results showed that (i) in both models, an early reduction in plasma insulin and prolactin levels occurred, and in the case of insulin, this reduction was sustained for a prolong period prior to tumor detection, indicating that recognition by the host of emergent tumor cells triggers an endocrine response; (ii) in contrast with multiply transplanted tumors, cells from early transplant generations produced no significant endocrine changes during latency; (iii) irrespective of whether they were primary or transplanted, large tumor burdens caused similar hormonal alterations, consisting of increased corticosterone and growth hormone and decreased insulin, thyroxin, prolactin and sex steroid levels in blood. Our comprehensive longitudinal study demonstrates host endocrine responses during different stages of neoplastic development.

A reduction in blood insulin levels as a host endocrine response during tumor development.

It has been previously reported that endogenous insulin levels decrease during tumor growth. We have now studied whether this host endocrine response is independent of the way in which the tumor is induced. For this purpose, animals transplanted with tumor cells induced by 3-methylcholanthrene (MCA) or 7,12-dimethylbenz(a) anthracene (DMBA), or with EL-4 lymphoma cells, and animals that develop autochthonous tumors induced by MCA or the murine mammary tumor virus (MMTV) were used. These procedures result in the induction of tumors of different histologic types: fibrosarcoma, mammary adenocarcinoma and lymphoma. The results obtained showed that a reduction in insulin levels preceded the overt appearance of tumors in all models of syngeneic or autochthonous tumors studied but not when DMBA-induced tumor cells were administered into allogeneic recipients. Reduced levels of insulin before tumor detection appeared to affect the onset of MCA-induced tumors. Indeed, those mice with a late tumor onset were those that had a more pronounced decrease in insulin blood levels during the induction phase of autochthonous MCA-induced tumors. Soluble factors associated with tumor growth seem to mediate the reduction in insulin blood levels in mice transplanted with EL-4 tumor cells. The results obtained indicate that the reduction in insulin levels detected is a consequence of the recognition of tumor cells by the host, and seems to be independent of the histologic type of the neoplastic cells that develop. Pharmacological interventions at the levels of mechanisms that control insulin output should clarify the relevance of decreased levels of this hormone for tumor development.

Polymorphic imprinting of the serotonin-2A (5-HT2A) receptor gene in human adult brain.

We have examined the imprinting status of the serotonin-2A (5-HT2A) receptor gene (HTR2A) in a series of 41 tissue samples from human adult brain. Using a HpaII RFLP polymorphism in the coding region, we obtained evidence of monoallelic expression of HTR2A in 4 out of 18 informative individuals. However, biallelic expression of HTR2A was observed in other individuals (14/18), suggesting that within the human population HTR2A imprinting in brain is polymorphic.

Prevention of postoperative pericardial adhesions using tissue-protective solutions.

Repeat cardiac surgical procedures are associated with increased technical difficulty and risk because of the previous formation of dense adhesions between the heart and the surrounding tissues. Dilute solutions of sodium hyaluronic acid (NaHA) and carboxymethyl cellulose (CMC) have been shown to prevent postoperative abdominal and pelvic adhesions and could therefore potentially inhibit adhesion formation following cardiac surgery. Adhesion prevention using 0.1% NaHA, 0.4% NaHA, or 0.1% CMC solutions was examined in a canine abrasion/desiccation pericardial adhesion model (5 animals/group) and compared to 10 animals treated with Ringer's lactate (RL) solution alone. The pericardium and heart were coated with 25 ml of test or control solution prior to and after pericardiotomy, after controlled gauze abrasion, after 30 min of desiccation, and prior to closure. At 6 weeks, animals were reexplored and adhesions were scored in a blinded manner by three to four surgeons using a 0-4 scale. Scores of 2 or greater were considered clinically significant. Mean adhesion scores from the left epicardium were 0.0 in animals treated with 0.1% NaHA, 0.6 in animals treated with 0.4% NaHA or 1% CMC, and 2.3 in animals treated with RL (P < 0.05 Duncan's ANOVA). In addition, none of the animals treated with 0.1% NaHA, 20% of the animals treated with 0.4% NaHA, and 20% of the animals treated with 1% CMC had clinically significant adhesions, whereas 80% of animals treated with RL had such adhesions. Sodium hyaluronic acid and CMC solutions, used as tissue coatings during cardiac surgery, inhibit the formation of undesired postoperative adhesions. Application of these biocompatible polymer solutions during surgery could reduce the technical difficulty and risk of repeat cardiac surgical procedures.

Tuberous sclerosis-like lesions in epileptogenic human neocortex lack allelic loss at the TSC1 and TSC2 regions.

Glioneuronal malformations with a striking histological resemblance to cortical tubers of tuberous sclerosis, but no extracerebral stigmata of this phacomatosis, are frequently encountered in patients with chronic pharmacoresistant epilepsies. It is controversial as to whether these lesion represent a forme fruste of tuberous sclerosis or a distinct entity. The recently reported loss of heterozygosity (LOH) at the regions of the TSC1 or TSC2 locus in hamartomas obtained from different organs of patients with established tuberous sclerosis, including cortical tubers, stimulated us to examine epilepsy-associated tuberous sclerosis-like glioneuronal malformations with respect to LOH at the TSC1 and TSC2 loci of chromosomes 9q34 and 16p 13.3, respectively. The analysis was carried out on DNA derived from paraffin-embedded brain tissues of 11 patients. For 5 patients, peripheral blood leukocytes were also available for DNA extraction. We performed microsatellite analysis with five markers on chromosome 9 and four markers on chromosome 16. In addition, polymerase chain reaction-restriction fragment length polymorphism (RFLP) analysis was performed using a polymorphic EcoRV restriction site in exon 40 of the TSC2 gene. No LOH was identified in any of the cases. These findings do not support a relationship between the epilepsy-associated glioneuronal lesions and tuberous sclerosis. However, tuberous sclerosis is genetically heterogeneous and microsatellite and RFLP analysis cannot exclude small deletions or point mutations. Thus, given the histopathological similarity of glioneuronal malformations in epilepsy patients to cortical tubers, further molecular genetic studies will be needed as our understanding of the molecular basis of tuberous sclerosis increases to completely clarify the relationship of these lesions to tuberous sclerosis.

Experimental and clinical allogeneic heart transplant rejection: correlations between histology and immune reactivity detected by cytokine messenger RNA.

BACKGROUND: Cytokines produced by host cells infiltrating allogeneic transplants are critical determinants of graft rejection but information on cytokine production during graft rejection remains limited. No reported study on cytokine profiles has compared experimental allograft rejection induced by withdrawal of cyclosporine with clinical transplant rejection that occurs in the presence of therapeutic levels of cyclosporine. METHODS: Functional activities of allograft-infiltrating host cells in sequential endomyocardial biopsies obtained before, during, and after acute heart transplant rejection were determined with the use of the reverse transcriptase-polymerase chain reaction to detect cytokine messenger RNA. These results were correlated with histologic findings in both an experimental canine model of heart transplant and rejection and in clinical human heart transplant recipients. RESULTS: When experimental rejection was induced by withdrawal of immunosuppression, rejection was characterized by the presence of mRNA encoding CD4, CD8, interleukin-2 (but not interleukin-4), interleukin-2 receptor, and tumor necrosis factor-beta. These findings are consistent with a classic T-helper, T-cytotoxic cell-mediated response. However, the cytokine profile of human, clinical heart transplant rejection occurring in the presence of therapeutic levels of immunosuppression differed strikingly. In clinical rejection in human beings, histologic evidence of rejection was not associated with detectable interleukin-2 or interleukin-2 receptor mRNA. CONCLUSIONS: Human, clinical heart rejection can occur in the absence of locally produced interleukin-2; the degree of immunosuppression achieved with cyclosporine A may explain the different results obtained in the canine withdrawal model versus human clinical allograft rejection.

Prolonged survival of a patient with left ventricular pseudoaneurysm following myocardial infarction and mitral valve replacement.

We present the case of a patient with left ventricular pseudoaneurysm following acute myocardial infarction. Survival for 2 years following diagnosis, despite the large size of the aneurysm, and subsequent management with cardiac transplantation represent unusual and interesting aspects of this complication of myocardial infarction.

Florida Poison Information Network. Saving lives and money.

A highly sophisticated network of poison information centers exists in Florida, one each in the northern, central and southern regions of the state. These 24-hour-a-day centers are staffed by nurses and pharmacists who provide assessment, triage and management advice about a wide range of exposures. Toxicologists are available when in-depth consultation is needed. As most cases can be safely managed at home, costly visits to the emergency room are averted, resulting in significant overall health-care savings. These centers also provide educational programs for the public and health professionals and compile epidemiologic statistics.

Modification of atrioventricular conduction using a combined laser-electrode catheter.

Ablation of the AV junction is an accepted technique for the management of selected supraventricular tachyarrhythmias. Radiofrequency ablation appears to be safe and effective for AV junction ablation in most patients, but the need for firm tissue contact may make it less effective for ventricular tachycardia and certain ectopic/atrial tachycardias. Laser energy can also be delivered through a catheter, and thus it may be an attractive alternative energy source for ablation. A new laser-electrode catheter was developed for modification of conduction through the AV node as a model for ablation of an arrhythmia substrate. A window for delivery of continuous-wave Nd:YAG laser energy was placed between the two electrodes of a bipolar electrode catheter. In vitro studies using a matrix of power versus time were performed to determine the energy that would create lesions of the appropriate size in vivo. Using this information, advanced AV block was successfully created in 16 of 17 dogs (94%) with the laser-electrode catheter. Advanced AV block was successfully created in all four dogs in the chronic study, and it persisted for 1-24 weeks of follow-up until sacrifice of the animals. Histologic examination demonstrated discrete thermal damage at the AV junction with no instances of septal perforation in the acute studies or progressive necrosis in chronically maintained dogs. Advanced AV block may be produced consistently and safely in dogs using a combined laser-electrode catheter.

Inhibition of atherosclerosis by dietary pectin in microswine with sustained hypercholesterolemia.

Sustained hypercholesterolemia is a known risk factor for development of atherosclerosis. In animal studies, grapefruit pectin fed concurrently with a high-lipid diet inhibits hypercholesterolemia and atherogenesis. The purpose of the present study was to determine if grapefruit pectin affects cholesterol levels and atherogenesis of animals with established hypercholesterolemia. Microswine were fed an atherogenic diet to establish hypercholesterolemia. Plasma cholesterol levels rose rapidly and for 360 days were sustained at levels 6- to 12-fold the normal level. Then, half the microswine, selected at random, were fed a diet in which 3% grapefruit pectin was substituted for cellulose, and the remaining animals received the original diet. Animals were killed 270 days later, and the extent of atherosclerosis was determined. In animals with established hypercholesterolemia, pectin did not lower their cholesterol levels. However, pectin reduced the extent of atherosclerosis in both the aorta and coronary arteries. The mean surface area covered by atherosclerosis in the aorta was 13.6% in the group that did not receive pectin compared with 5.3% in the group that did receive pectin. The mean coronary artery narrowing was 45% without pectin and 24% with pectin. We conclude that pectin may have a direct beneficial effect on atherosclerosis by a mechanism independent of cholesterol levels.

Rotational atherectomy for treatment of occluded prosthetic grafts.

Potentially, percutaneous rotational atherectomy (RA) can be used to open occluded prosthetic arterial bypass grafts with less morbidity than surgical catheter thrombectomy. However, RA could damage prosthetic grafts or produce significant distal emboli. To investigate this, acutely thrombosed and chronically occluded prosthetic grafts, harvested from dogs, were placed in an ex vivo perfusion system and recanalization was attempted using the TRAC-Wright rotational atherectomy system. Urokinase (UK) was delivered through the RA catheter in one-half of the procedures. Graft surface thrombogenicity and graft mechanical integrity after successful recanalization were determined and debris released during recanalization was collected. Results were compared to those from grafts opened by catheter thrombectomy. One hundred percent (22/22) of acute prosthetic graft occlusions and 39% (16/41) of chronic prosthetic graft occlusions were opened using RA, similar to results achieved using catheter thrombectomy. In addition, surface thrombogenicity after recanalization of acute graft occlusion with RA was lower than that after catheter thrombectomy (P < 0.05) and infusion of UK improved RA success in chronically occluded grafts (52% vs 25%). Debris generated during RA averaged 15-18 micrograms, equivalent to debris generated during catheter thrombectomy, and graft mechanical integrity was unaffected by recanalization using RA. Thus, rotational atherectomy is a minimally invasive means of safe and effective prosthetic graft recanalization that produces a less thrombogenic graft than thrombectomy.

Acetaminophen ingestion in childhood--cost and relative risk of alternative referral strategies.

Acetaminophen is the pharmaceutical most frequently ingested by small children. Although past research has allowed the safe management of 90% of these ingestions at home, several thousand are still referred to emergency departments annually. With the goal of further reducing the number of unnecessary referrals, the risk/benefit considerations of alternate referral strategies were analyzed. In a retrospective poison center chart review study from 11 centers, the records of children between the ages 1 and 6 years who acutely ingested acetaminophen and were referred to a hospital for determination of serum acetaminophen concentration in 1986 and 1987 were identified using the database of the American Association of Poison Control Centers. Risk of hepatic injury was assigned on the basis of the Rumack-Matthew acetaminophen toxicity nomogram. The cohort was stratified in terms of the amount ingested and whether a pediatric or adult preparation was ingested. The direct cost of an evaluation was estimated from four centers. Sensitivity, specificity and direct cost of each risk identification strategy were calculated. Eight hundred sixty six of 2091 patients had a timed serum acetaminophen concentration recorded. Of these, three patients had results in the "probable risk" area of the nomogram. A referral reduction strategy which would refer only children who ingest 200 mg/kg or more of an adult preparation could eliminate 82% of referrals without missing any of these "probable risk" patients. Six other children were determined to have serum acetaminophen concentrations in an area of the nomogram labeled "possible risk". No referral reduction strategy explored identified all of these patients. The average charge for an emergency department evaluation in 1992 was $272.00. These data suggest that children less than six years of age who ingest pediatric acetaminophen products other than those from packages containing greater than 30 tablets or who ingest less than 200 mg/kg of an adult preparation may be safely managed at home without referral to a hospital. This strategy would result in significant cost savings and prevent unnecessary inconvenience to many patients and families.

Influence of time until emesis on the efficacy of decontamination using acetaminophen as a marker in a pediatric population.

STUDY OBJECTIVE: To determine the extent of drug removal by emesis at different times after the ingestion of a toxic substance. DESIGN: Multicenter retrospective chart review. METHODS: Using the American Association of Poison Control Centers' aggregate data base, children who had ingested acetaminophen and who were referred to a health care facility by one of 11 poison centers during a two-year period were identified. Charts of these patients were reviewed to determine the quantity ingested per kilogram of body weight, method of decontamination used, the timing of decontamination, and the serum acetaminophen concentration obtained four hours after ingestion. RESULT: Charts of 455 patients met all requirements for inclusion. When emesis occurred within one-half hour after ingestion, mean serum acetaminophen concentration drawn four hours after ingestion was approximately half that in a control group that received no decontamination. Emesis had less impact when it was delayed further and had no demonstrable impact when it occurred more than 90 minutes after ingestion. CONCLUSION: Many factors must be considered when deciding if and by what method a given patient should receive decontamination. When delayed gastric emptying is not expected, emesis can at best decrease a toxic burden by half if it occurs early. Medical care givers must continue to scrutinize management practice to ensure that syrup of ipecac is given only in situations in which it is likely to make a difference in outcome and in which it is the most effective agent to achieve this goal.

Origin of cells in the coronary intima during acute vascular rejection of the transplanted human heart.

Acute vascular rejection of the coronary arteries in human heart transplants is characterized by a lymphocytic infiltrate and a thickened intima that contains numerous highly vacuolated cells. The origin of the vacuolated cells has been controversial. In this immunocytochemical and electron microscopic study of four patients with acute vascular rejection, the predominant cells in the coronary artery intima were host-derived lymphocytes and highly vacuolated smooth muscle cells. Lymphocytic infiltrates were composed of T cells with variable numbers of B cells. Macrophages were infrequent. Smooth muscle cells were identified by their reactivity to muscle-specific actin and ultrastructural features of a peripherally displaced elongated nucleus associated with abundant myofibrils. In addition, the vacuolated cells did not react with endothelial factor 8-related antigen or Ulex europaeus agglutinin, as would be expected of endothelial cells. The cytoplasmic vacuoles present in the smooth muscle cells appear to be swollen endoplasmic reticulum containing watery fluid consistent with the hypothesis that they result from altered ion movement across the plasma membrane in response to cellular injury.