Gingival Fibroma: An Emerging Distinct Gingival Lesion with Well-Defined Histopathology.

Gingival growths, barring a few are mostly reactive and seldom exhibit significant true neoplastic potential. The common etiology is local irritation from dental plaque/calculus, trauma as well as medication-related overgrowth. Such lesions are easily distinguishable and categorized into diagnoses such as pyogenic granuloma, peripheral ossifying fibroma, etc. We present a previously undescribed, but commonly encountered, reactive gingival growth with unique histologic features and suggest the diagnostic term "gingival fibroma." An IRB approved retrospective review of the University of Florida Oral Pathology Biopsy Service encompassing years 2010-2019, was performed to select cases. Demographics, clinical data, and microscopic diagnoses were recorded and analyzed. Four board-certified oral and maxillofacial pathologists agreed upon and established the diagnostic criteria. These are: a prominent fibromyxoid stroma, variable cellularity, a whorled or storiform pattern of arrangement of the cellular elements, lack of significant inflammation or vascularity, and complete absence of calcification, and/or odontogenic islands. A total of 60 cases met all criteria and were included in the study. Age range in years was 14-87 with the mean at 45.11 years. A striking female predilection (90%) was noted. Approximately 62% of cases were reported on the maxillary gingiva, followed by 38.3% in the mandibular gingiva. Majority, 66.7% were in the anterior incisor region followed by 11.7% in the canine/first premolar areas. All lesions were submitted as excisional biopsy, and 4 cases recurred within 2-3 years of excision. In all cases, lesional tissue appeared to extend to the surgical base of the specimen. We present 60 cases of a histologically unique entity occurring exclusively on the gingiva and introduce the diagnostic term "Gingival Fibroma" for these lesions. Further studies with adequate clinical follow-up may help understand the exact clinical behavior of these lesions.

Odontogenic Myxoma: A 23-Year Retrospective Series of 38 Cases.

Odontogenic myxoma (OM) is an uncommon benign odontogenic tumor arising in the jaw. Though it has slight histologic overlap with other entities, definitive diagnosis is imperative considering the tumor's aggressive nature, high recurrence rate, and necessity of radical surgical intervention in large-sized lesions. With IRB approval, a retrospective search of the University of Florida College of Dentistry Oral Pathology Biopsy Service archives from 1994 to 2017 for diagnosis of OM of the jaw was performed. Biopsy reports and original slides for each case were assessed and reviewed along with any accompanying radiographs to confirm the diagnosis. Immunohistochemical staining was utilized to exclude entities with histologic overlaps, such as intraosseous myxoid neurofibroma. A total of 38 cases were included. The patients' age ranged from 6 to 84 years, with a mean age of 37.47 years. Females comprised two-thirds of the cases (n = 25) versus males (n = 13). The mandible was the most affected at 60.5% (n = 23), followed by maxilla 39.4% (n = 15). Posterior jaw involvement was higher than anterior in both the mandible (n = 20 versus n = 3) and the maxilla (n = 11 versus n = 4). Most lesions presented clinically as expansile masses with variable radiographic appearance. The clinical impression from submitting providers included "gelatinous masses", abscesses, odontogenic lesions, fibro-osseous lesions, soft tissue or bone neoplasms, and reactive gingival lesions. A consensus of odontogenic myxoma as a diagnosis was rendered for 30 cases (79%), while in 8 cases (21%) that exhibited a more fibrous stroma was identified as fibromyxoma. OM may exhibit a varied demographic and clinical profile with a wide spectrum of histologic presentations. Pathologists should be sentient of this variability in order to arrive at an accurate diagnosis and correctly manage these patients.

An Analysis of Clinical and Histopathologic Features of Fibrous Dysplasia of the Jaws: A Series of 40 Cases and Review of Literature.

Fibrous dysplasia (FD) is a rare condition commonly involving the jaws. While FD has a typical clinical and histological presentation, considerable variation exists. Moreover, overlap of features with other disorders is possible. This study serves to characterize the features of a large case series of FD of the jaws. With IRB approval, the University of Florida Oral Pathology Biopsy Service archive was retrospectively searched from 1994 to 2015 for cases of FD. Epidemiological data, location, duration, clinical and radiographic appearance, clinical impression and exact microscopic diagnosis were recorded. The average age was 37.3 years (range 7-87 years) with majority of cases in females (67.5%). The most common ethnicity was Caucasian. Maxillary location was predominant (59%), followed by mandible (38%) and multiple locations (3%). Expansion was reported in 78% of cases. Radiographically, most cases exhibited ground glass opacity, however some presented with a mottled or mixed radiopaque/radiolucent appearance. Histologically, a wide variation in terms of stromal cellularity, presence of osteoblastic rimming, and presence of calcified material mimicking cemento-osseous dysplasia was observed. Clinicians and pathologists should be cognizant of the significant variability in clinical, histopathologic, and radiographic presentation of FD, which may pose a diagnostic challenge.

Lichenoid Characteristics in Premalignant Verrucous Lesions and Verrucous Carcinoma of the Oral Cavity.

Verrucous hyperkeratosis (VH), verrucous carcinoma (VC) and the relentless, truly pre-malignant variant proliferative verrucous leukoplakia often exhibit lichenoid histologic features that may create a diagnostic dilemma for pathologists. This study aims to evaluate and categorize the frequency and the histopathologic patterns of lichenoid features seen in these lesions. Following IRB approval, cases of VH and VC from 1994 to 2014 were retrieved from the archives of UF Oral Pathology Biopsy Service. A panel of 4 board-certified oral and maxillofacial pathologists reviewed and scored the presence or absence of 5 lichenoid features: band-like infiltrate (BLI), saw tooth rete ridges (STRR), interface stomatitis (IS), civatte bodies (CB), and basement membrane degeneration (BMD). Cases not fulfilling the stringent selection criteria were excluded. A total of 70 cases of VH and 56 cases of VC were included. Approximately 25% of both VH and VC cases exhibited 3 or more lichenoid features. By Chi square testing, BLI (p = 0.000), IS (p = 0.005), and CB (p = 0.026) were significantly more common in VC than VH. Gingival lesions had significantly less frequent BLI (p = 0.004) and IS (p = 0.024) versus other sites. However, STRR was significantly more common in VH than VC (p = 0.000) in the gingiva. (p = 0.002). Statistical analysis revealed that the only significant valid association was the increased presence of band-like infiltrate in VC over VH (p = 0.001). Lichenoid features are common in both VH and VC and may represent a nonspecific inflammatory response to the dysplasia or malignancy rather than concomitant lichenoid disease. This could lead to significant under diagnoses of these premalignant or potentially malignant lesions by pathologists.

Effect of patient and nurse ethnicity on emergency department analgesia for children with appendicitis in israeli government hospitals.

BACKGROUND: Ethnicity is a risk factor for disparate Emergency Department (ED) analgesia. We aimed to explore ethnic variations in the administration of ED analgesia to children with acute appendicitis in Israeli government hospitals. METHODS: Children discharged with an International Classification of Disease-Ninth Revision diagnosis of acute appendicitis between 2010 and 2015 were included. The association between patient ethnicity (Jewish, Arab) and analgesia administration (any, opioid) was assessed. Age, gender, triage category, pain score and time of arrival were tested as possible confounders. The effect of patient-nurse ethnic discordance (PNED) was examined. RESULTS: Overall, 4714 children with acute appendicitis, 3520 Jewish and 1194 Arab, were cared for in the EDs; 1516 (32.2%) received any analgesia and 368 (7.8%) opioid analgesia. Stratified by pain score, no statistical differences were found in the administration of any or opioid analgesia between Jewish and Arab patients with either severe pain or moderate pain. In multivariate modelling adjusted for pain score and triage category, the rates of any analgesia for Arab and Jewish patients were 31.8% (95% CI, 30.9-32.6) and 36.5% (95% CI, 36.0-36.9), adjusted OR (aOR) = 1.16 (95% CI, 0.98-1.38), respectively. The rates of opioid analgesia for Arab and Jewish patients were 8.5% (95% CI, 8.2-8.9) and 7.9% (95% CI, 7.3-8.7), aOR = 0.77; (95% CI, 0.59-1.22), respectively. Jewish and Arab nurses treated proportionally fewer patients from the opposite ethnicity with any analgesia (p < 0.01). CONCLUSION: Emergency Department analgesia was markedly low, and not associated with patient ethnicity. PNED was associated with decreased rates of analgesia. SIGNIFICANCE: Emergency Department analgesia for children with acute appendicitis in Israeli government hospitals is markedly low. Patient-provider ethnic discordance may negatively influence the provision of analgesia. Significant efforts should be undertaken in order to increase analgesia provision rates and reduce social inequality.

Direct immunofluorescence testing results in cases of premalignant and malignant oral lesions.

OBJECTIVES: Oral premalignant and malignant lesions may mimic oral lichen planus (OLP) clinically and microscopically. OLP often shows basement membrane fibrinogen positivity on direct immunofluorescence testing (DIF). This study examined fibrinogen positivity in oral premalignant lesions and squamous cell carcinoma. STUDY DESIGN: The University of Florida Oral Pathology Biopsy Service records were searched for the years 2003 to 2013 for oral premalignant lesions and squamous cell carcinoma with concurrent DIF testing. Demographic, clinical, and DIF or histologic information was collected and analyzed. RESULTS: Sixty-eight fibrinogen positive lesions were identified within a total of 164 cases. Low-grade dysplasia and premalignant verrucous lesions made up the majority of the fibrinogen positive lesions (combined n = 43; 63.2%), and the most common locations in positive cases were the buccal mucosa, tongue, and gingiva. A lichenoid distribution of the inflammatory infiltrate significantly predicted fibrinogen positivity (P < .0005). CONCLUSIONS: Fibrinogen positivity may be seen in premalignant and malignant oral lesions increasing the risk of misdiagnosis.

A mutation creating an out-of-frame alternative translation initiation site in the GRHPR 5'UTR causing primary hyperoxaluria type II.

Primary hyperoxaluria type II is a recessive genetic disorder caused by mutations in the GRHPR gene. Although several dozen mutations have been described, all affect coding or transcript splicing. A man suspected of having primary hyperoxaluria type II was heterozygous for a novel single-nucleotide deletion (c.694delC) in GRHPR affecting Gln(232) , which introduced a pre-mature termination (p.Gln232Argfs*3). Two 5'untranslated region (UTR) variants of unknown significance were also noted. We show that these two variants occur in cis, on the opposite allele, and introduce - immediately upstream of the canonical translation initiation site - a novel out-of-frame translational start site. In vitro studies using the GRHPR 5'UTR fused to a luciferase reporter show that the variant start site pre-empted initiation at the canonical translational start site, and this was corroborated within the broader context of 1.3 kb of the GRHPR proximal promoter. This latter mechanism may be underappreciated in general; reports of clinically significant functional variation of this type are extremely rare.

Desmoplastic fibroma of the mandible: a series of three cases and review of literature.

The desmoplastic fibroma (DF) is a rare, fibroblastic lesion of bone that histologically resembles the desmoid tumor of soft tissue. Although classified as benign, it frequently demonstrates aggressive behavior, often causing tooth mobility, extensive bone destruction, and has a moderate to high recurrence rate. We present three cases of DF in the mandible: the first in a 13 year old female involving the mandibular body in the region of teeth #s 27-#28, the second in a 57 year old female with a lesion apical to tooth #30, and the third in a 20-year-old female involving the left posterior mandible. Clinical, histologic, immunohistochemical (IHC) and radiographic features of this rare neoplasm are discussed. The challenges encountered in establishing an accurate diagnosis due to significant microscopic overlap with other spindle cell lesions are also detailed. Additionally, the findings of IHC stains including vimentin, smooth muscle actin, S-100 protein, ß-catenin, HHF-35 and proliferation marker, Ki-67 on 3 cases are reported. The potential for misdiagnosis is high, especially in early lesions, since immunohistochemistry has been reported in literature to be inconsistent when differentiating DFs from other spindle cell lesions. A comparative review of DF and similar entities in the jaws with current considerations in treatment and prognosis is presented.

Intraoral basal cell carcinoma, a rare neoplasm: report of three new cases with literature review.

Intraoral basal cell carcinoma (IOBCC) is an extremely rare entity that bears close microscopic resemblance to and is often confused with the peripheral ameloblastoma (PA). Basal cell carcinomas are thought to arise from pluripotential basal cells present within surface epithelium and adnexal structures, so theoretically they can arise within the oral cavity. Many of the early cases reported as IOBCC actually represent PA. Most of the well documented cases arise from the gingiva. The histologic features of basal cell carcinoma that help separate it from a PA include: tumor arising from surface epithelium, scattered mitotic figures and apoptotic cells, presence of mucoid ground substance and tumor infiltrating widely throughout the connective tissue and often exhibiting a prominent retraction artifact. Clinically IOBCC resemble carcinomas, compared to the benign and innocuous appearance of the PA and typically presents as surface ulcerations varying from rodent ulcer to an ulcerated erythroplakia appearance. This contrasts with the classic "bump on the gum" appearance of PAs with usually intact surface and appearing as small discrete, sessile, exophytic lesions. Importantly, the proliferative basaloid epithelium demonstrates positive immunoreactivity for the anti-epithelial antibody, Ber-EP4, a cell surface glycoprotein. The IOBCC has the potential for local recurrence and aggressive behavior and should be treated with wide surgical excision and close clinical follow up. We present 3 rare cases of IOBCC and discuss the salient histologic, immunohistochemical and clinical features.

Bizarre parosteal osteochondromatous proliferation (Nora's Lesion) of the mandible. a rare bony lesion.

Bizarre parosteal osteochondromatous proliferation (BPOP) also eponymically called "Nora's lesion", is a rare benign reactive bone lesion first reported in 1983. BPOP occurs classically on the bones of the hands and feet and long bones. This lesion can easily be confused, both clinically and microscopically, with other benign and malignant lesions of bone, including osteochondroma, parosteal osteosarcoma, myositis ossificans and reactive periostitis. BPOP has been reported to have a high rate of recurrence. Only 3 cases of BPOP of the head and neck have been reported in the literature, of which one involved the maxilla. We present a rare case of BPOP involving the mandible in a 10 year old African American male. Microscopically, a fibro-cartilaginous cap giving rise to a proliferation of variably mineralized osteophytic finger-like projections of bone was seen. Multiple trabeculae of "blue bone" were noted as well as numerous atypical appearing chondrocytes. The lesion recurred within 4 months following the initial excision but has not recurred to date after the second local excision. To the best of our knowledge, this is the first report of BPOP arising in the mandible. In addition, we discuss the clinical and microscopic features, differential diagnosis, and prognosis of this rare entity. We present a case of BPOP of the mandible and believe this is the first report of such a case in the mandible.

Anatomic site based ploidy analysis of oral premalignant lesions.

The location of oral leukoplakia correlates strongly with the probability of finding dysplastic or malignant alterations at biopsy. It is well established that early detection can dramatically improve the 5-year survival rates for oral squamous cell carcinomas. Since aneuploidy is predictive of future conversion to malignancy, we hypothesized that dysplastic lesions from high-risk sites (floor of mouth, tongue and lips) would exhibit greater aneuploidy than low-risk sites (palate, gingiva and buccal mucosa). Epithelial sections from 60 archival samples diagnosed as mild dysplasia (36 females, 20 males) from various high/low risk locations were stained with Blue Feulgen Stain for DNA Ploidy Analysis (Clarient, Aliso Viejo, CA) and ploidy was analyzed using a ChromaVision ACIS II (Clarient, ALiso Viejo, CA) Image cytometry system. A DNA histogram was generated using an image analyzing software that evaluated the amount of Feulgen stain which is proportional to the amount of nuclear DNA. An ANOVA analysis followed by the Student's't' test revealed significant differences between means (P

Chronic ulcerative stomatitis: diagnostic and management challenges--four new cases and review of literature.

Chronic ulcerative stomatitis (CUS) is a recently described mucocutaneous disease characterized by involvement of mucosal surfaces and skin. The disease usually presents in the form of painful oral ulcers and has been seen predominantly among older women. Clinically, CUS patients may exhibit erosive or ulcerative lesions of oral mucosa resembling erosive lichen planus and/or other vesiculobullous lesions. Routine histology may exhibit features of lichenoid mucositis and is often nondiagnostic. Direct immunofluorescence studies of mucosal or skin biopsies usually reveal a unique pattern of IgG bound to nuclei of keratinocytes of the basal and parabasal cell layers. Chronic ulcerative stomatitis exhibits a unique resistance to standard treatments available, including topical and systemic corticosteroids and immunomodulatory medications. However, long-lasting favorable clinical responses may be achieved with hydroxychloroquine pharmacotherapy. We present the clinicoimmunopathologic findings of four cases of CUS and discuss the varied clinical, microscopic spectrum, and treatment for this chronic, debilitating, and often recalcitrant condition. A systematic review of the literature, including 35 previously reported cases, is presented.

Physician handwashing: what do parents want?

Transmission of micro-organisms from the hands of healthcare workers to patients is a major cause of healthcare-acquired infections. In 2002, the US Centers for Disease Control and Prevention (CDC) published guidelines for healthcare workers that included the recommendation for alcohol-based hand rub for hand hygiene during patient visits. In this prospective study we surveyed parental and healthcare workers' preferences for the hand hygiene practices of emergency physicians. The study comprised 99 parents of ill or injured children presenting to our emergency department and 100 healthcare providers (64 nurses, 29 physicians and seven nurse practitioners) within the department. There was a clear and similar preference by parents and healthcare workers for hand hygiene using soap and water over alcohol cleansing rubs. Furthermore, both groups preferred hand hygiene before and after the examination and wanted to observe the physician perform this procedure. In conclusion, families and healthcare worker preferences for hand hygiene are not in keeping with recommendations published by the CDC. Educational interventions are needed to disseminate the CDC's guidelines and to promote compliance with evidence-based recommendations for hand hygiene.

[Attention deficit-hyperactivity disorder or juvenile mania]. / Trouble déficit de l'attention/hyperactivité ou manie de l'enfant.

In recent years, the relationship between juvenile mania and attention deficit hyperactivity disorder has been the focus of renewed clinical research and controversial debates. We have reviewed the recent literature about bipolar disorder and juvenile mania in children in order to clarify the knowledge in assessment, phenomenology and diagnosis of prepubertal bipolar disorder. Despite the fact that prepubertal mania has been recognized, there is no consensus on the diagnostic criteria. The symptomatic overlap and comorbidity of juvenile mania with attention deficit hyperactivity disorder has produced confusion. As prospective studies are not yet contributive because of the heterogeneity of samples and criteria, one cannot consider these manic children as truly cases of bipolar disorder.

Urea and hypertonicity increase expression of heme oxygenase-1 in murine renal medullary cells.

Epithelial cells derived from the mammalian kidney medulla are responsive to urea at the levels of signal transduction and gene regulation. Hybridization of RNA harvested from control- and urea-treated murine inner medullary collecting duct (mIMCD3) cells with a cDNA expression array encoding stress-responsive genes suggested that heme oxygenase (HO)-1 mRNA was upregulated by urea. RNase protection assay confirmed this upregulation; hypertonicity also increased HO-1 mRNA expression but neither hypertonic NaCl nor urea were effective in the nonrenal 3T3 cell line. The effect on HO-1 expression appeared to be transcriptionally mediated on the basis of mRNA half-life studies and reporter gene analyses using the promoters of both human and chicken HO-1. Although urea signaling resembles that of heavy metal signaling in other contexts, the effect of urea on HO-1 transcription was independent of the cadmium response element in this promoter. Urea-inducible HO-1 expression was sensitive to antioxidants but not to scavengers of nitric oxide. Urea also upregulated HO-1 protein expression and pharmacological inhibition of HO-1 action with zinc protoporphyrin-sensitized mIMCD3 cells to the adverse effects of hypertonicity but not to urea. Coupled with the prior observation of others that HO-1 expression increases along the renal corticomedullary gradient, these data suggest that HO-1 expression may comprise an element of the adaptive response to hypertonicity and/or urea in renal epithelial cells.

Recurrent ingrown toenails secondary to indinavir/ritonavir combination therapy.

OBJECTIVE: To report five cases of ingrown toenails (IGTN) associated with indinavir/ritonavir (IDV/RTV) combination therapy. CASE SUMMARY: The median onset of IGTN from initiation of IDV/RTV therapy was 18.4 weeks. Four patients previously received IDV, with one of these experiencing prior IGTN. All patients required surgical management of IGTN. All patients received virologic benefit from ongoing antiretroviral therapy, and the majority of patients elected to maintain IDV/RTV combination therapy. Two patients experienced recurrent IGTN while receiving ongoing IDV/RTV combination therapy. DISCUSSION: IGTN and paronychia have previously been reported with IDV and lamivudine. IGTN in patients with HIV infection is more likely to present acutely, involve more digits, and require surgical management IDV increases retinoic acid signaling and, based on elevated IDV concentrations from concomitant RTV therapy, the risk of IGTN may be increased in patients receiving IDV/RTV combination therapy. CONCLUSIONS: With the increasing popularity of IDV/RTV combination therapy, clinicians should be aware of the potential increase in frequency of dose-related toxicities including IGTN. Evaluation of hands and feet on physical examination should be recommended for all patients being treated with lamivudine and IDV, especially when used in combination with RTV.

Evidence of hypertriglyceridemia in managing HIV patients on efavirenz.

Of the recently approved antiretroviral agents, efavirenz has become a popular medication for the treatment of HIV infection. The efficacy of an efavirenz-based regimen has allowed the use of a combination of this medication with other antiretroviral agents in all levels of HIV disease, resulting in decreased viral replication and positive clinical results. Efavirenz is also proposed as an acceptable agent to switch to from a protease inhibitor-based regimen to reduce the risk of metabolic complications. In addition, the favorable side-effect profile, diminished pill burden for clients, and daily dosing have contributed to its popularity. Primary care practitioners should be cognizant of the possible side-effect profile of antiretroviral therapy combinations and enter into a collaborative relationship with the infectious disease clinician to ensure safe and effective patient care.

Urea inhibits hypertonicity-inducible TonEBP expression and action.

Tonicity-responsive genes are regulated by the TonE enhancer element and the tonicity-responsive enhancer binding protein (TonEBP) transcription factor with which it interacts. Urea, a permeant solute coexistent with hypertonic NaCl in the mammalian renal medulla, activates a characteristic set of signaling events that may serve to counteract the effects of NaCl in some contexts. Urea inhibited the ability of hypertonic stressors to increase expression of TonEBP mRNA and also inhibited tonicity-inducible TonE-dependent reporter gene activity. The permeant solute glycerol failed to reproduce these effects, as did cell activators including peptide mitogens and phorbol ester. The inhibitory effect of urea was evident as late as 2 h after the application of hypertonicity. Pharmacological inhibitors of known urea-inducible signaling pathways failed to abolish the inhibitory effect of urea. TonEBP action is incompletely understood, but evidence supports a role for proteasome function and p38 action in regulation; urea failed to inhibit proteasome function or p38 signaling in response to hypertonicity. Consistent with its effect on TonEBP expression and action, urea pretreatment inhibited the effect of hypertonicity on expression of the physiological effector gene, aldose reductase. Taken together, these data 1) define a molecular mechanism of urea-mediated inhibition of tonicity-dependent signaling, and 2) underscore a role for TonEBP abundance in regulating TonE-mediated gene transcription.

Valvular hemodynamics and arrhythmias with exercise following the Ross procedure.

Pulmonary autograft aortic valve replacement (Ross procedure) is increasing in popularity, particularly in children and young adults. We performed a controlled study of pediatric and adult Ross procedure patients to evaluate postoperative exercise valvular hemodynamics and cardiac rhythm. Thirty-one patients and 24 controls underwent stress echocardiography. Doppler and 2-dimensional echocardiography assessed valvular hemodynamics and right and left ventricular size at baseline and after exercise. Electrocardiography monitored cardiac rhythm. Patients and controls had neoaortic and neopulmonic valve insufficiency ranging from none to moderate that improved or did not change with exercise. Baseline and exercise mean peak transaortic gradients were not significantly different between patients (baseline 6.3 +/- 3.8 mm Hg, exercise 12.8 +/- 7.3 mm Hg) and controls (baseline 6.7 +/- 2.5 mm Hg, exercise 14.3 +/- 5.2 mm Hg). However, baseline and exercise mean peak transpulmonic gradients were significantly different between patients (baseline 20.7 +/- 9.6 mm Hg, exercise 45.2 +/- 23.5 mm Hg) and controls (baseline 3.7 +/- 1.3 mm Hg, exercise 10.6 +/- 3.7 mm Hg). Significant exercise-induced arrhythmias occurred in 8 patients (26%) and no controls. Occurrence of arrhythmias correlated with an older age at surgery and age at study. After the Ross procedure, patients have valve competence and transaortic gradients similar to controls at baseline and with exercise. However, patients have significantly increased baseline and exercise transpulmonic gradients compared with controls. Furthermore, exercise-induced arrhythmias occurred frequently in our patient group and were associated with an older age at surgery and age at study.

Regional differences in mechanisms of cerebral circulatory response to neuronal activation.

Vibrissal stimulation raises cerebral blood flow (CBF) in the ipsilateral spinal and principal sensory trigeminal nuclei and contralateral ventroposteromedial (VPM) thalamic nucleus and barrel cortex. To investigate possible roles of adenosine and nitric oxide (NO) in these increases, local CBF was determined during unilateral vibrissal stimulation in unanesthetized rats after adenosine receptor blockade with caffeine or NO synthase inhibition with N(G)-nitro-L-arginine methyl ester (L-NAME) or 7-nitroindazole (7-NI). Caffeine lowered baseline CBF in all structures but reduced the percent increase during stimulation only in the two trigeminal nuclei. L-NAME and 7-NI lowered baseline CBF but reduced the percent increase during stimulation only in the higher stations of this sensory pathway, i.e., L-NAME in the VPM nucleus and 7-NI in both the VPM nucleus and barrel cortex. Combinations of caffeine with 7-NI or L-NAME did not have additive effects, and none alone or in combination completely eliminated functional activation of CBF. These results suggest that caffeine-sensitive and NO-dependent mechanisms are involved but with different regional distributions, and neither fully accounts for the functional activation of CBF.