Subclinical to catastrophic: a range of outcomes in cerebral air embolism.

Cerebral air embolism (CAE) is a rare, yet potentially devastating condition characterized by entrance of air into cerebral vasculature, that is nearly always iatrogenic. While many findings of CAE are subclinical and incidental at computed tomography (CT), there remain cases of catastrophic and fatal embolisms. Increasing physician awareness of prevention, presentation, and treatment for CAE is crucial for reducing morbidity and mortality. In this case series, we highlight this preventable entity by comparing three cases of CAE that showcase a diverse array of presentations, radiologic findings, and clinical outcomes. We will also explore predisposing factors, prognostic predictors, diagnostic considerations, and available treatments.

Congress of neurological surgeons systematic review and evidence-based guidelines update on the role of cytoreductive surgery in the management of progressive glioblastoma in adults.

QUESTION: In patients with previously diagnosed glioblastoma who are suspected of experiencing progression, does repeat cytoreductive surgery improve progression free survival or overall survival compared to alternative interventions? TARGET POPULATION: These recommendations apply to adults with previously diagnosed glioblastoma who are suspected of experiencing progression of the neoplastic process and are amenable to surgical resection. RECOMMENDATION: Level II: Repeat cytoreductive surgery is recommended in progressive glioblastoma patients to improve overall survival.

The impact of maternal obesity on iron status, placental transferrin receptor expression and hepcidin expression in human pregnancy.

BACKGROUND: Obesity is associated with decreased iron status, possibly due to a rise in hepcidin, an inflammatory protein known to reduce iron absorption. In animals, we have shown that maternal iron deficiency is minimised in the foetus by increased expression of placental transferrin receptor (pTFR1), resulting in increased iron transfer at the expense of maternal iron stores. OBJECTIVE: This study examines the effect of obesity during pregnancy on maternal and neonatal iron status in human cohorts and whether the placenta can compensate for decreased maternal iron stores by increasing pTFR1 expression. SUBJECTS/METHODS: A total of 240 women were included in this study. One hundred and fifty-eight placentas (Normal: 90; Overweight: 37; Obese: 31) were collected at delivery. Maternal iron status was measured by determining serum transferrin receptor (sTFR) and ferritin levels at 24 and 34 weeks and at delivery. Hepcidin in maternal and cord blood was measured by ELISA and pTFR1 in placentas by western blotting and real-time RT-PCR. RESULTS: Low iron stores were more common in obese women. Hepcidin levels (ng ml(-1)) at the end of the pregnancy were higher in obese than normal women (26.03±12.95 vs 18.00±10.77, P<0.05). Maternal hepcidin levels were correlated with maternal iron status (sTFR r=0.2 P=0.025), but not with neonatal values. mRNA and protein levels of pTFR1 were both inversely related to maternal iron status. For mRNA and all women, sTFR r=0.2 P=0.044. Ferritin mRNA levels correlated only in overweight women r=-0.5 P=0.039 with hepcidin (r=0.1 P=0.349), irrespective of maternal body mass index (BMI). CONCLUSIONS: The data support the hypothesis that obese pregnant women have a greater risk of iron deficiency and that hepcidin may be a regulatory factor. Further, we show that the placenta responds to decreased maternal iron status by increasing pTFR1 expression.

Minimally Invasive Bilateral Duo-Keyhole Approach for Giant Falcine Meningioma: 2 Dimensional Operative Video.

One of the key concepts behind minimally invasive keyhole cranial surgery is that as the operative corridor deepens, it also widens. The corridor should therefore be designed parallel to the long-axis of the tumor to optimize visualization.1 These ideas were applied in a duo-keyhole operation for a falcine meningioma. The patient is a 79-year-old woman diagnosed with a large falcine meningioma compressing both frontal lobes. Her tumor was oriented with the long-axis, perpendicular to the superior sagittal sinus, and has bulbous extensions on both sides of the falx. Incisions on the falx, anterior and posterior to the tumor, in addition to a cut between it and the undersurface of the superior sagittal sinus, would render it practically devascularized and "free-floating.2" One keyhole was insufficient, but one anterior and another posterior to the tumor would make the falcine cuts feasible. The operation was performed with the above scheme and the posterior keyhole to the left and anterior one to the right of midline to facilitate surface vascular detachment on both sides. The patient recovered well and was discharged home after 4 days. This procedure highlights that flexible application of the principles of minimally invasive keyhole. Neurosurgery can tailor-make an operation to precisely fit the unique features of a patient and the tumor. The procedure was performed under the ethical guidelines of our hospital. No Institutional Review Board consent was required or sought because the patient gave specific consent to the procedure and publication of her image.

Minimally Invasive Lateral Transorbital Approach for Clipping of Right Middle Cerebral Artery Aneurysm: 2-Dimensional Operative Video.

The lateral transorbital approach is a minimally invasive approach that was first described for accessing the cavernous sinus.1 Although other minimally invasive approaches have been broadly applied to aneurysm surgery,2 the use of transorbital keyholes for this is still quite rare.3,4 We present a 72-year-old man with an incidentally discovered 5-mm middle cerebral artery aneurysm. Despite a low rupture risk,5 the patient himself opted for treatment, and because of the complex shape of the aneurysm, he chose surgical clipping as the treatment of choice. Two unique aspects of the patient's anatomy brought forth transorbital approach for consideration. He had a wide fissure, which opened to the orbital wall, and a giant frontal sinus made its avoidance difficult with any anterolateral transcranial approach. The lateral transorbital approach was started with a transpalpebral incision.4,6,7 Both wings of the sphenoid bone were drilled until the frontal and temporal dura was exposed. Opening this through the orbit gained direct access to the large Sylvian fissure. Two specific challenges were specific to this opening: the aneurysm dome pointed straight at the surgeon, and the M1 segment, needed for proximal control, was directly behind the aneurysm. Despite these, the aneurysm was successfully eliminated through the transorbital approach with no residual or normal branch compromise. Given the specific anatomical provisions, the lateral transorbital approach was an effective and safety alternative to the pterional approach for middle cerebral artery aneurysms. No Institutional Review Board approval was sought or necessary as the patient provided consent for the procedure, publication of his image, and this submission.

Agreement of activity monitors for assessment of patients with sub-acute stroke in an inpatient rehabilitation facility.

PURPOSE: Determine the level of agreement of three activity monitors compared with the gold standard (video review) on the activity level of patients with stroke. METHODS: A prospective, observational, agreement study was performed on 47 individuals with sub-acute stroke in an inpatient rehabilitation facility. Data was collected during one physical therapy session. Individuals wore three device types; Actigraph (AG), Activpal (AP), and stepwatch activity monitor (SAM). Variables assessed were step counts for each limb (hemiparetic and non-hemiparetic) and percent time standing and other. ANALYSIS: Results from the activity monitors were compared to the video review and assessed for agreement using the intraclass correlation coefficient (ICC) and accuracy of mean difference from video observation. RESULTS: The step counts with the SAM on the non-hemiparetic limb had the highest ICC for step counts (ICC = 0.98, p < 0.001) and were overestimated with 21% accuracy. The SAM on the hemiparetic limb had 9.7% accuracy (ICC = 0.92, p < 0.001). For percent standing time all devices overestimated with poor reliability. For percent other activity time, the AP had the best accuracy and underestimated for both the hemiparetic limb (9.9% accuracy; ICC = 0.90, p < 0.001) and non-hemiparetic limb (8.3% accuracy; ICC = 0.84, p < 0.001). CONCLUSIONS: The use of multiple devices may be warranted to capture an accurate understanding of activity levels in this population of individuals with sub-acute stroke. There are concerns with all monitors and clinicians and researchers should be aware of what measures they are wanting to understand about their population.

The stepwatch activity monitor worn on the hemiparetic limb provided the best accuracy and excellent reliability for step counts in this population of subacute stroke.For percent standing time all devices overestimated with poor reliability.For percent other time, the AP had the best accuracy and good reliability on the non-hemiparetic limb.The use of multiple devices may be warranted to capture a more accurate understanding of activity level in this population of individuals with sub-acute stroke.Clinicians and researchers need to be aware of the biases of these devices in this population.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on the Management of Progressive Glioblastoma in Adults: Update of the 2014 Guidelines.

BACKGROUND: The Institute of Medicine best practice recommendation to review guidelines every 5 years is followed by the Congress of Neurological Surgeons Guidelines Committee. The aim of this work was to provide an updated literature review and evidence-based recommendations on the topic of diagnosis and treatment of patients with progressive glioblastoma (pGBM). OBJECTIVE: To review the literature published since the last guidelines on pGBM dated 2014, with literature search ending in June 2012. METHODS: PubMed, Embase, and Cochrane were searched for the period July 1, 2012, to March 31, 2019, using search terms and search strategies to identify pertinent abstracts. These were then screened using published exclusion/inclusion criteria to identify full-text review articles. Evidence tables were constructed using data derived from full-text reviews and recommendations made from the evidence derived. RESULTS: From the total 8786 abstracts identified by the search, 237 full-text articles met inclusion/exclusion criteria and were included in this update. Two new level II recommendations derived from this work. For the diagnosis of patients with GBM, the use of diffusion-weighted images is recommended to be included in the magnetic resonance images with and without contrast used for surveillance to detect pGBM. For the treatment of patients with pGBM, repeat cytoreductive surgery is recommended to improve overall survival. An additional 21 level III recommendations were provided. CONCLUSION: Recent published literature provides new recommendations for the diagnosis and treatment of pGBM. The Central Nervous System Guidelines Committee will continue to pursue timely updates to further improve the care of patients with diagnosis.https://www.cns.org/guidelines/browse-guidelines-detail/guidelines-management-of-progressive-glioblastoma.

Change in EEG Activity is Associated with a Decrease in Tinnitus Awareness after rTMS.

OBJECTIVE: To examine how 1Hz and 10Hz rTMS temporarily influence ratings of tinnitus loudness, annoyance, and awareness. The thalamocortical dysrhythmia (TCD) model of tinnitus was tested by examining changes in spectral power and coherence of resting state EEGs from baseline to each phase of treatment and correlating these data with change in tinnitus. METHODS: Nineteen participants completed a double-blind, placebo (sham rTMS) controlled, within-subjects study with crossover between the two active rTMS treatment conditions. An imposed order effect, sham rTMS first, eliminated drift of active treatment into the placebo condition. The primary outcome measures were analogue ratings of tinnitus loudness, annoyance, and awareness, assessed repeatedly at baseline and during treatment, and 64 channel, resting state EEGs collected at baseline and the end of each treatment phase. Active rTMS consisted of 1800 pulses at 110% of motor threshold over temporal cortex delivered at 1Hz and 10Hz over four days. The research design also examined the effect of rTMS immediately following stimulation, regression to the mean in tinnitus ratings made over multiple days, and differences between treatment responders and non-responders. RESULTS: There was no immediate effect of rTMS on tinnitus during a single rTMS session. Regression to the mean in tinnitus ratings occurred over three days of baseline and four days of treatment (both sham and active rTMS). After accounting for regression to the mean in the statistical model, 1Hz rTMS led to a significant decrease in tinnitus awareness from baseline and 10Hz rTMS trended in the same direction, whereas sham rTMS showed little change from baseline other than regression to the mean. Changes from baseline in spectral power of the resting state EEG provided partial support for predictions based on TCD model of tinnitus for active 1 and 10Hz rTMS but not sham rTMS. However, only an increase in beta coherence correlated significantly with a decrease in tinnitus awareness. Changes in the EEG were robust in treatment responders but absent among non-responders and during sham rTMS. CONCLUSIONS: A positive response to rTMS for tinnitus is associated with an rTMS-induced change in beta coherence of the EEG. Increased beta coherence may be a biomarker of the rTMS effect; a "top-down" modulation of the EEG that promotes habituation to tinnitus. Participants whose tinnitus did not improve after rTMS did not show any changes in the EEG.

The α5-GABAAR inverse agonist MRK-016 upregulates hippocampal BDNF expression and prevents cognitive deficits in LPS-treated mice, despite elevations in hippocampal Aß.

Alzheimer's disease is marked by the presence of amyloid-beta (Aß) plaques, elevated central cytokine levels, dysregulation of BDNF-related gene expression, and cognitive decline. Previously, our laboratory has demonstrated that repeated administration of peripheral LPS is sufficient to significantly increase the presence of central Aß in the hippocampus, and that this upregulation corresponds with deficits in learning and memory. We have also previously demonstrated that the inverse benzodiazepine agonist MRK-016 (MRK) can protect against memory acquisition and consolidation errors in mice. To extend these findings, the current study explored the protective effects of MRK in the context of LPS-induced hippocampal Aß accumulation. Hippocampal Aß was significantly elevated, relative to saline-treated animals, following seven days of peripheral LPS injections. Animals were then trained in a contextual fear conditioning paradigm and were immediately treated with MRK or saline once training was complete. Behavioral testing occurred the day after training. Results from this study demonstrate that repeated injections of LPS significantly elevate hippocampal Aß, and inhibit acquisition of contextual fear. Post-training treatment with MRK restored behavioral expression of fear in LPS-treated animals, despite elevated hippocampal Aß, an effect that may be attributed to increased BDNF mRNA expression. Therefore, our data indicate that MRK can prevent LPS- induced cognitive deficits associated with elevated Aß, and restore hippocampal BDNF expression.

Successful treatment of ventricular assist device associated ventricular thrombus with systemic tenecteplase.

We report a case of intracardiac thrombus in a patient supported by the Jarvik 2000 Flowmaker successfully treated with a single dose of peripherally administered TNK-tissue plasminogen activator (Tenecteplase, Metalyse, Boehringer Ingelheim). This strategy may be considered in the case of life-threatening VAD associated thrombosis to avoid the need for intracardiac drug delivery or VAD replacement. We also discuss the apparent increased thrombotic risk in patients receiving a VAD for chemotherapy induced cardiomyopathy and the implications this may have for the choice of VAD.

In rats gestational iron deficiency does not change body fat or hepatic mitochondria in the aged offspring.

Mitochondrial dysfunction and resulting changes in adiposity have been observed in the offspring of animals fed a high fat (HF) diet. As iron is an important component of the mitochondria, we have studied the offspring of female rats fed complete (Con) or iron-deficient (FeD) rations for the duration of gestation to test for similar effects. The FeD offspring were ~12% smaller at weaning and remained so because of a persistent reduction in lean tissue mass. The offspring were fed a complete (stock) diet until 52 weeks of age after which some animals from each litter were fed a HF diet for a further 12 weeks. The HF diet increased body fat when compared with animals fed the stock diet, however, prenatal iron deficiency did not change the ratio of fat:lean in either the stock or HF diet groups. The HF diet caused triglyceride to accumulate in the liver, however, there was no effect of prenatal iron deficiency. The activity of the mitochondrial electron transport complexes was similar in all groups including those challenged with a HF diet. HF feeding increased the number of copies of mitochondrial DNA and the prevalence of the D-loop mutation, however, neither parameter was affected by prenatal iron deficiency. This study shows that the effects of prenatal iron deficiency differ from other models in that there is no persistent effect on hepatic mitochondria in aged animals exposed to an increased metabolic load.

Strategy of aggressive steroid weaning and routine alendronate therapy to reduce bone loss after cardiac transplantation.

OBJECTIVE: Osteoporosis is common after cardiac transplantation. The routine use of prednisolone posttransplantation is a major contributor to bone mineral loss. We sought to study the effectiveness of a strategy combining aggressive steroid weaning and routine prophylaxis with alendronate to reduce bone loss without adversely affecting posttransplantation survival. PATIENTS AND METHODS: This retrospective clinical study compared 2 cohorts of patients. Group A included 28 patients who had undergone transplantation since June 1999, all of whom were prescribed alendronate (10 mg daily or 70 mg weekly). All were aggressively weaned off prednisolone with the aim of being steroid-free by 9 months posttransplantation. Only 10 of the 28 patients were on prednisolone at the time of the study. Group B was an historical control cohort of 28 posttransplant patients reviewed in a cross-sectional study in 1995. Only 2 patients were on osteoporosis prophylaxis with estrogen or vitamin D; 26 patients were on prednisolone at the time of the study. The groups were compared by dual-energy X-ray absorptiometry (DEXA) bone mineral densitometry at the femoral neck and lumbar spine at a mean of 3 years after transplantation. We compared the cumulative survival of the 2 groups. RESULTS: Cumulative survival posttransplantation was similar in both groups. Compared with group B, group A showed a significantly higher mean femoral Z-score (+0.3 vs -0.5, P=.01) and lumbar spine Z-score (0.0 vs -0.9, P<.02). The incidence of osteoporosis (defined by WHO criteria as T-score

Neural activity during attentional conflict predicts reduction in tinnitus perception following rTMS.

BACKGROUND: Subjective idiopathic tinnitus is an intrusive, distracting, and potentially disabling disorder characterized by phantom perception of sounds. Although tinnitus has no approved pharmacologic treatment, recent evidence supports the use of repetitive transcranial magnetic stimulation (rTMS) to alleviate tinnitus symptoms. OBJECTIVE/HYPOTHESIS: Repetitive TMS delivered over the middle superior temporal gyrus (STG) may alter ratings of tinnitus awareness and annoyance more than loudness due to change in attentional processing. STG has reciprocal connections to regions of the prefrontal cortex that mediate attention. To probe the hypothesized influence of STG stimulation on attention, a subset of patients with tinnitus enrolled in an rTMS clinical trial [n = 12, 9 male, mean (sd) age = 49 (15) years] underwent an attentional conflict task before and after rTMS treatment in a repeated-measures functional magnetic resonance imaging (fMRI) study. METHODS: The Multi-Source Interference Task (MSIT), a Stroop-based visual attentional conflict fMRI task, was used to map participants' neural processing of attentional conflict prior to rTMS intervention (Baseline) and after three rTMS intervention arms: Sham, 1 Hz, and 10 Hz (four sessions per arm, 1800 pulses per session, delivered @110% of the motor threshold over the posterior superior temporal gyrus). RESULTS: All measures of tinnitus severity (awareness, loudness, and annoyance) improved with 1 Hz rTMS intervention; however, the greatest and most robust changes were observed for ratings of tinnitus awareness (mean 16% reduction in severity from Baseline, p < 0.01). The MSIT elicited a similar pattern of neural activation among tinnitus participants at Baseline compared to an independent sample of 43 healthy comparison adults (r = 0.801, p = 0.001). Linear regression with bootstrap resampling showed that greater recruitment of bilateral prefrontal and bilateral parietal regions by MSIT at Baseline corresponded with poorer treatment response. Individual regions' activities explained 37-67% variance in participant treatment response, with left dorsolateral prefrontal cortex's MSIT activity at Baseline explaining the greatest reduction in tinnitus awareness following 1 Hz stimulation. Although left dorsolateral prefrontal cortex activity at Baseline also predicted reduction in tinnitus loudness and annoyance (∼50% variance explained), these symptoms were more strongly predicted by right middle occipital cortex (∼70% variance explained) - suggesting that the neural predictors of symptom-specific treatment outcomes may be dissociable. CONCLUSION: These candidate neural reactivity markers of treatment response have potential clinical value in identifying tinnitus sufferers who would or would not therapeutically benefit from rTMS intervention.

Late humoral rejection in a cardiac transplant recipient treated with the anti-CD20 monoclonal antibody rituximab.

Humoral or vascular rejection results from a B cell-mediated production of immunoglobulin (Ig) G antibody against a transplanted organ, producing immune complex deposition on the vascular endothelium, activation of the complement cascade, generation of endothelial dysfunction, and regional ischemic injury. Antibody-mediated rejection, which may be accompanied by hemodynamic compromise, is associated with reduced long-term graft survival. Patients believed to be at an increased risk of developing humoral rejection include women, particularly those with high levels of panel reactive antibodies, cytomegalovirus seropositivity, and positive cross matches, and subjects with prior sensitization to OKT3. Treatment options for humoral rejection include plasmapheresis to lower the circulating immunoglobulin levels followed by high-dose cyclophosphamide to reduce the B-cell population. Other modalities include total lymphoid irradiation, photophoresis, splenectomy, and, for treatment failures, retransplantation. Rituximab is a chimeric humanized monoclonal antibody directed against the pan B-cell surface molecule, CD20. It is approved for the treatment of low-grade B-cell non-Hodgkin's lymphoma. It has also been used successfully for the treatment of posttransplant B-cell lymphoproliferative disease. We report a case of late humoral rejection successfully treated with rituximab.

Canine thyroid neoplasms: epidemiologic features.

A retrospective study of medical records from twelve veterinary university hospitals-clinics yielded 144 dogs with a confirmed diagnosis of a thyroid neoplasm (25 adenomas and 119 carcinomas). Forty-five of these dogs had additional primary neoplasms. As in man, associated tumors suggested the inherited multiple endocrine adenomatosis, type 1, and a possible syndrome of thyroid and chemoreceptor lesions. Although the female preponderance of human thyroid cancer was not seen in dogs, females showed a much sharper increase in risk with advancing age than did males. Three breeds (beagle, boxer, and golden retriever) had a significantly greater risk for thyroid carcinoma than did all dogs combined, whereas miniature and toy poodles had a low risk. The function of thyroiditis in the origin of thyroid cancer, as suggested by reports of thyroid carcinoma in people with Hashimoto's disease, may be clarified by follow-up studies of beagles which are prone to Hashimoto-type thyroiditis.

Excess of seminomas observed in Vietnam service U.S. military working dogs.

During the Vietnam War, US military working dogs served with their companion dog handlers in close proximity, sharing common exposures to war-related activity, many zoonotic infectious agents, chemical pesticides, phenoxy herbicides, and extensive use of therapeutic drugs. To gain insight into the effects of the Vietnam experience, we investigated the occurrence of neoplasms in military working dogs based on standard necropsy examination by the Armed Forces Institute of Pathology. We observed that these dogs experienced significant elevated risks for testicular seminoma and, independently, testicular dysfunction. Experimental evidence shows testicular dysfunction and impaired spermatogenesis in laboratory animals exposed to phenoxy herbicides, dioxin, or tetracycline, and antibiotic used extensively in military working dogs in Vietnam. Because an unexplained significant decrease in sperm quality in Vietnam veterans has been observed by the Centers for Disease Control, further research is warranted if we are to clarify military service in Vietnam as a risk factor for testicular dysfunction. The testis should be made a priority site in the study of Vietnam experience-related cancers.

Case-control study of canine malignant lymphoma: positive association with dog owner's use of 2,4-dichlorophenoxyacetic acid herbicides.

A hospital-based case-control study of companion dogs examined the risk of developing canine malignant lymphoma associated with the use of chemicals in and about the home. Information from a self-administered owner questionnaire and/or a telephone interview of about 491 cases, 466 nontumor controls, and 479 tumor controls indicated that owners in households with dogs that developed malignant lymphoma applied 2,4-dichlorophenoxyacetic acid (2,4-D) herbicides to their lawn and/or employed commercial lawn care companies to treat their yard significantly more frequently than control owners (odds ratio = 1.3). In addition, the risk of canine malignant lymphoma rose to a twofold excess with four or more yearly owner applications of 2,4-D. The findings in this study are consistent with occupational studies in humans, which have reported modest associations between agricultural exposure to 2,4-D and increased risk of non-Hodgkin's lymphoma, the histology and epidemiology of which are similar to those of canine malignant lymphoma. The present study suggests that human health implications of 2,4-D exposure in the home environment should receive further investigation.

Epidemiological features of canine renal neoplasms.

A retrospective study of medical records from 13 veterinary university hospitals and clinics yielded 73 cases of confirmed primary neoplasms of the kidney and renal pelvis. Analysis of the 34 cases of renal carcinoma revealed no evidence of familial (breed) predisposition, but an excess risk was identified in males, especially during middle life. The morphological and epidemiological features of canine renal carcinoma are similar to those of renal carcinoma in humans. The dog may be a suitable model for further research into the causes of this cancer.

Hormone-dependent neoplasms of the canine perianal gland.

The epidemiological features of 472 dogs with microscopically confirmed neoplasms of the perianal gland are described. These general characteristics suggest etiological factors similar to those responsible for hormone-related neoplasms occurring in human beings. Perianal gland tumors appear to be androgen dependent. Male dogs show a 5.6-fold-increased risk compared with females; endogenous estrogens offer protection and the use of estrogenic hormones is conventional therapy for the benign lesion. Both sexes of the cocker spaniel breed show excessively high risk, suggesting that this dog family may be a model for genetic studies that could be relevant to familial aggregations of hormone-related tumors in men and women. Adrenocortical hormones may play a role in the development of the tumor in female dogs. Research into alterations of the biochemical pathways of steroidogenesis in affected female dogs may provide clues to similar conditions in humans.

Selective immunosuppression in mice of natural killer cell activity by ochratoxin A.

Ochratoxin A, a naturally occurring mycotoxin, has recently been shown to cause renal and hepatic carcinomas in mice. In the present studies, the effects of ochratoxin A on immune mechanisms associated with tumor resistance were examined in mice using dose levels similar to those that cause neoplasia. Ochratoxin A was shown to specifically inhibit natural killer (NK) cell activity and increase the growth of transplantable tumor cells without altering T-cell- or macrophage-mediated antitumor activity. In contrast, ochratoxin B, a much less toxic ochratoxin, did not influence immune function. Polyinosinic:polycytidylic induced interferon was markedly reduced in mice following exposure to ochratoxin A although total serum protein levels were slightly increased. Injection of polyinosinic:polycytidylic enhanced NK activity in the presence of ochratoxin A, although the level of enhancement was slightly lower than that produced by the agent in the absence of ochratoxin A. Thus, ochratoxin appears to suppress NK cell activity by inhibiting production of basal interferon. Additionally, these findings suggest a possible role for altered NK cell function in the development of mycotoxin-induced carcinogenesis.