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Biomedical subjects

D Greenspan

Publications and source records attributed to D Greenspan.

At least 37 records · Page 2Linked to original sources

Chemokine gene expression in human oral mucosa.

In order to gain further understanding of the role of chemokines in healthy oral mucosa, we analyzed mRNA expression of the alpha (CXC)-family chemokines IL-8 and GROgamma as well as of the beta (CC)-family chemokines MIP-1alpha, MIP-1beta and MCP-1 in twenty young and healthy subjects with good oral hygiene. Twenty biopsies were taken from clinically healthy oral mucosa before surgical removal of impacted wisdom teeth. In addition, five biopsies from patients presenting with specific oral lesions were studied. RNA was purified, quantitated and utilized as substrate for competitive reverse transcription-polymerase chain reaction (RT-PCR). In healthy tissue, IL-8 and MCP-1 mRNA was constitutively expressed in all biopsies, whereas GROgamma, MIP-1alpha, and MIP-1beta were significantly lower. These findings suggest that IL8 and MCP-1 play a significant role in oral tissue homeostasis. The few samples from pathological conditions encourage exploring diseased tissue in more detail.

Adolescent↗

In vivo analysis of secreted aspartyl proteinase expression in human oral candidiasis.

Secreted aspartyl proteinases are putative virulence factors in Candida infections. Candida albicans possesses at least nine members of a SAP gene family, all of which have been sequenced. Although the expression of the SAP genes has been extensively characterized under laboratory growth conditions, no studies have analyzed in detail the in vivo expression of these proteinases in human oral colonization and infection. We have developed a reliable and sensitive procedure to detect C. albicans mRNA from whole saliva of patients with oral C. albicans infection and those with asymptomatic Candida carriage. The reverse transcription-PCR protocol was used to determine which of the SAP1 to SAP7 genes are expressed by C. albicans during colonization and infection of the oral cavity. SAP2 and the SAP4 to SAP6 subfamily were the predominant proteinase genes expressed in the oral cavities of both Candida carriers and patients with oral candidiasis; SAP4, SAP5, or SAP6 mRNA was detected in all subjects. SAP1 and SAP3 transcripts were observed only in patients with oral candidiasis. SAP7 mRNA expression, which has never been demonstrated under laboratory conditions, was detected in several of the patient samples. All seven SAP genes were simultaneously expressed in some patients with oral candidiasis. This is the first detailed study showing that the SAP gene family is expressed by C. albicans during colonization and infection in humans and that C. albicans infection is associated with the differential expression of individual SAP genes which may be involved in the pathogenesis of oral candidiasis.

AIDS-Related Opportunistic Infections↗

Safety needles.

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California↗

Risk factors for chemotherapy-induced oral mucositis: dental appliances, oral hygiene, previous oral lesions, and history of smoking.

Oral mucositis is one of the dose-limiting toxicities of several chemotherapy (CTX) agents. There are suggested risk factors that could influence the development of mucositis. The presence of dental appliances, history of oral lesions, or smoking have the potential to irritate the oral mucosa and produce breaks in the integrity of the mucosa. The purposes of this study were to determine if there were differences in the incidence, severity, and time to onset of CTX-induced mucositis in oncology outpatients who wore dental appliances, had a history of oral lesions, had varying oral hygiene/care practices, and had a history of smoking and those who did not. Patients who were initiated a course of CTX that included stomatotoxic agents were followed for three complete cycles of CTX. They were instructed on how to examine their mouths for mucositis, to contact, and then visit their outpatient settings if it occurred. Clinicians corroborated the presence of mucositis, and the Eiler's Oral Assessment Guide was used by clinicians to determine the severity. Of 332 outpatients, almost half (46%) wore some type of dental appliance, 32% had a history of oral lesions, 10% were currently smoking, and 63% had a history of smoking. Oral hygiene/care practices varied: 81% brushed their teeth two or more times a day, 29% flossed at least daily, 11% had visited their dentist within 2 months of beginning CTX, and 10% had their teeth professionally cleaned within two months of beginning CTX. There was a 31% (n = 104) incidence of CTX-induced mucositis. No significant differences were found in the incidence between patients who wore dental appliances, had a history of oral lesions, had a history of smoking, and practiced different hygiene/care and patients who did not. Of 104 patients who developed mucositis, the average severity rating was 13.05 +/- 2.88 (+/-SD) (a normal mouth is rated at 8) and the average time to onset was 22.3 +/- 21.46 days. There were no significant differences found in severity or time to onset of mucositis between patients who wore dental appliances, had a history of oral lesions, had a history of smoking, and practiced different dental hygiene/care and patients who did not. Although not significant, there were interesting differences in the time to onset across the suggested risk factors (e.g., patients who had visited a dentist or who had their teeth professionally cleaned within 2 months before beginning before CTX developed mucositis 7.4 and 10.6 days sooner, respectively, than patients who did not). These findings suggest that risk factors for the development of CTX-induced mucositis are not as simple and direct as clinicians may believe.

Adult↗

Histologic observations of periodontal wound healing after treatment with PerioGlas in nonhuman primates.

The effect of PerioGlas (synthetic bone particulate) on wound healing of experimental palatal periodontal defects in monkeys was evaluated. Chronic periodontal defects were created on the palatal aspects of maxillary molars and premolars. Open-flap debridement was performed. Experimental sites received PerioGlas, while control sites received no further treatment. Histologic measurements were performed on new bone, new cementum, epithelial downgrowth, and recession. Results showed significantly more new cementum and less epithelial downgrowth in the sites that received PerioGlas (P < 0.05). The present results indicate that PerioGlas may enhance periodontal wound healing outcomes.

Alveolar Bone Loss↗

Randomized trial of itraconazole oral solution for oropharyngeal candidiasis in HIV/AIDS patients.

PURPOSE: Oropharyngeal candidasis (thrush) is the most common opportunistic infection in individuals who are positive for the human immunodeficiency virus (HIV) and those who have progressed to AIDS. Itraconazole has a broad in vitro spectrum of activity, including a wide variety of Candida species. Our study determined the relative efficacy of a new oral solution formulation of itraconazole and fluconazole tablets in the treatment of oropharyngeal candidiasis. PATIENTS AND METHODS: This was a prospective randomized, third-party-blind, multicenter trial conducted at 12 centers in the United States. One hundred seventy-nine HIV-positive patients with mycologically documented oropharyngeal candidiasis were treated with itraconazole oral solution 200 mg/ day for 7 or 14 days, or fluconazole tablets 100 mg/day for 14 days. Severity of disease was scored clinically before treatment and at clinical evaluations on days 3, 7, 14, 21, 35, and 42. Semi-quantitative cultures of mouth washings were also obtained on these days. RESULTS: Both 14-day and 7-day regimens of itraconazole oral solution were equivalent to fluconazole for most efficacy parameters. The clinical response rate was 97% after 14 days of itraconazole and 87% after 14 days of fluconazole. Itraconazole oral solution given for 7 days was also equivalent to fluconazole treatment for 14 days. Approximately one half of patients in all three groups relapsed by 1 month after completion of treatment. There were few adverse reactions to either drug. CONCLUSION: Itraconazole oral solution is well tolerated and offers an alternative at least as effective as fluconazole in the treatment of oropharyngeal candidiasis.

AIDS-Related Opportunistic Infections↗

The PRO-SELF Mouth Aware program: an effective approach for reducing chemotherapy-induced mucositis.

Many oncology patients receive chemotherapy drugs that have the potential to induce oral mucositis. If mucositis is not prevented, patients will have to manage the problems associated with mucositis: pain, local infection, and decreased ability to take fluids or food. At the time of this writing, clinical approaches for mucositis management are variable and generally ineffective. The mouth care program, PRO-SELF: Mouth Aware (PSMA), presented in this article, was found to be a significant component of a self-care program that may have reduced the incidence of chemotherapy-induced mucositis. The PSMA program has three dimensions: (a) didactic information, (b) development of self-care exercises (skills), and (c) supportive interactions with a nurse in the setting where the patients are receiving their treatment. This program focuses on decreasing the direct (i.e., incidence and severity of mucositis) and indirect morbidities of oral mucositis (i.e., number of local infections, level of discomfort/pain, and disruption in fluid and/or food intake). It provides the critical dimensions (i.e., specific information, self-care exercises, and nurse support) to promote the prevention of mucositis. The PSMA program is designed to provide patients with a definitive self-care repertoire to manage chemotherapy-induced mucositis in the home without the direct supervision of a health care provider.

Antineoplastic Agents↗

Bromodeoxyuridine incorporation and Ki 67 expression in oral hairy leukoplakia.

OBJECTIVES: Oral hairy leukoplakia (HL) is an acanthotic, hyperparakeratotic lesion characterised by the presence of a replicative Epstein-Barr virus (EBV) infection in the superficial and adjoining layers of the epithelium. EBV or its gene products are capable of modifying epithelial differentiation. The aim of this study was to establish whether the presence of EBV was associated with an alteration in cell turnover by assessing bromodeoxyuridine (BrdU) incorporation and Ki 67 expression in lesional tissue and control mucosa. METHODS: Biopsies of HL together with age, site and sex matched controls (n = 7 and 8 respectively) were incubated in 200 microM BrdU in vitro, fixed in methacarn and processed to paraffin wax. Following acid hydrolysis, incorporated BrdU and Ki 67 were identified in serial 5 microns sections using a three-stage immunoperoxidase technique and cell density expressed as the number of positive cells per mm basement membrane length. RESULTS: Overall, there was no difference in the number of BrdU positive cells per mm basement membrane length between control and HL tissue. However, within HL alone, the presence of focal EBV replication was associated with a significant reduction in the number of basal cells incorporating BrdU compared to adjacent EBV free areas (P < 0.05). There was no significant difference between Ki 67 positive cells in control and HL tissue and no evidence of a reduction of Ki 67 positive cells in areas associated with EBV replication. CONCLUSIONS: These results suggest that there is no evidence of a generalised alteration of the proliferative capacity of basal cells in HL, although the focal reduction in BrdU incorporation may reflect subtle changes on cell turnover by EBV infection.

Adult↗

Association of cutaneous and oral diseases in HIV-infected men.

OBJECTIVES: Mucocutaneous diseases are common in patients infected with human immunodeficiency virus (HIV). To identify cutaneous diseases for which HIV-infected people are at high risk, we sought those that are strongly associated with specific HIV-related oral lesions and with progression of HIV disease. DESIGN: A cross-sectional study of HIV-positive outpatients referred to a university stomatology clinic for diagnosis and treatment of oral diseases. Each subject underwent both complete oral and cutaneous examinations. RESULTS: Among 55 men, with a median age of 41 years and a median CD4 cell count of 125/microliter (range 0-950/microliter), 93% had active oral diseases or conditions, including candidiasis, hairy leukoplakia, ulcers, Kaposi's sarcoma (KS), and xerostomia, and 95% had skin conditions, including onychomycosis, dermatophytosis, seborrheic dermatitis, KS, folliculitis, xerosis, and molluscum contagiosum. Seborrheic dermatitis, xerosis, skin KS, and molluscum contagiosum were associated with oral HIV-sentinel lesions (oral candidiasis, hairy leukoplakia, and KS), with low CD4 cell counts, and with AIDS. CONCLUSION: Our results suggest that xerosis and seborrheic dermatitis may be early harbingers of HIV disease progression. Their roles as predictors warrant further study, based on their associations with low CD4 cell counts and AIDS and strong co-prevalence with one of the most common HIV-related oral lesions, oral candidiasis.

AIDS-Related Opportunistic Infections↗

Comparison of cytopathic changes in oral hairy leukoplakia with in situ hybridization for EBV DNA.

OBJECTIVE: It has been observed that the cytopathic changes in hairy leukoplakia (HL) correlate with ultrastructural evidence of intra-keratinocyte herpes-type viral particles. In situ hybridization is considered to be the definitive confirmation of Epstein-Barr virus (EBV)-induced HL. This study evaluated the consistency of histopathological findings, which many believe to be diagnostic, with in situ hybridization for EBV-DNA in 60 patients with lesions clinically suggestive of HL. MATERIALS AND METHODS: Hematoxylin and eosin (H&E)-stained sections were reviewed independently by three oral pathologists who did not know the hybridization results. The presence in keratinocytes of nuclear inclusions and/or homogenization, believed to be specific for EBV in these lesions, was used as an indicator for infection. Cytoplasmic changes were evaluated separately. RESULTS: With in situ hybridization, 48 cases were positive and 12 were negative. When the two methods were compared, pathologist concurrence ranged from 83% to 92%. False negatives ranged from 6% to 19%, and false positives ranged from 8% to 25%. Cytoplasmic ballooning, homogenization, and perinuclear clearing were evident in all cases of hybridization-confirmed HL; however, these changes were also noted in 75% (9/12) of the cases with negative hybridization results. Most confirmed HL cases exhibited both nuclear homogenization and inclusions, although the former was more consistently seen. CONCLUSION: Cytoplasmic changes did not agree well with EBV-DNA hybridization results, whereas nuclear changes demonstrated good, but not complete, agreement. In appropriate clinical settings, the finding of nuclear inclusions and/or homogenization may be of diagnostic value. However, because the potential for false positives and negatives is high, H&E cytopathology should not be used as a substitute for in situ hybridization in the definitive diagnosis of oral hairy leukoplakia.

Cytopathogenic Effect, Viral↗

Stromal fibroblasts influence oral squamous-cell carcinoma cell interactions with tenascin-C.

In this study we identified tenascin-C (TN-C) and one of its integrin receptors, alpha(v)beta6, in oral squamous-cell carcinoma (SCC) specimens. Neither TN-C nor alpha(v)beta6 are expressed in normal oral mucosa. We also studied 2 human oral squamous-cell carcinoma cell lines: the highly invasive HSC-3 cells, and the poorly invasive SCC-25 cells. We determined that adhesion of these cells to TN-C involves both alpha2 and alpha(v) integrins. Migration on TN-C by oral SCC cells required fibroblast-conditioned medium and did not occur in its absence. This migration was blocked by anti-alpha2 and anti-alpha(v) antibodies and was partially inhibited by antibodies to hepatocyte growth factor, epidermal growth factor and transforming growth factor-beta1. When seeded on TN-C, the poorly invasive SCC-25 cells formed alpha(v)beta6-positive focal contacts; the HSC-3 cells did not. HSC-3, SCC-25 and PTF cells secrete TN-C into the culture medium, as determined by Western blot. However, when HSC-3 cells were inoculated into the floor of the mouth of nude mice, only murine TN-C could be identified in the reactive stroma adjacent to the resulting tumor nests, demonstrating that in vivo, HSC-3 cells do not secrete TN-C. Our results demonstrate that alpha(v)beta6 and tenascin-C are neo-expressed in oral squamous-cell carcinoma, and that the tumor stromal environment is influential in oral SCC behavior.

Animals↗

Effect of cigarette smoking on HIV-related oral lesions.

To determine whether the presence of specific oral lesions is associated with cigarette smoking among HIV-infected patients, we analyzed cross-sectional data (CD4 cell count, smoking history, and oral examination findings) from 1,058 HIV-infected male patients who received clinical care at the University of California, San Francisco. Oral AIDS Center Clinic. To control for potential confounding by the level of immune suppression, final analyses were limited to participants (n = 693) on whom CD4 cell count data (within 180 days of study visit) were available. Six percent of subjects had normal examination findings, 16% had nonnormal findings (but none of the six lesions of interest), 47% had lesions of a single type, and 31% had a combination of two or more types of lesions. After adjusting for CD4 cell count, current smokers were significantly more likely to have candidiasis (odds ratio [OR] = 1.84; 95% confidence interval [CI] 1.34-2.54) and warts (OR = 2.09; 95% CI 1.15-3.81) and less likely to have aphthous ulcers (OR = 0.24; 95% CI 0.14-0.42) than were current nonsmokers. These results suggest a strong association between cigarette smoking and the presence of specific HIV-related oral lesions.

Adolescent↗

Development of oral lesions in human immunodeficiency virus-infected transfusion recipients and hemophiliacs.

The authors used multivariate repeated-measures transition models to identify risk factors for two oral lesions related to human immunodeficiency virus (HIV)-candidiasis and hairy leukoplakia-in 152 HIV-infected blood transfusion recipients and hemophiliacs. Subjects were examined for occurrences of these lesions every 6 months from July 1985 through March 1993, yielding 1,076 study visits. It was found that, after adjustment for the CD4:CD8 T-lymphocyte ratio, patients with a history of candidiasis in the previous 18 months were at high risk of lesion recurrence. This risk increased with the number of prior episodes and with the recency of the episode(s). A history of hairy leukoplakia was less predictive of persistence of that lesion after adjustment for significant risk factors (including candidiasis and use of antifungal agents at the current examination, a low CD4:CD8 cell ratio, and age less than 40 years). The authors also found a high coprevalence of candidiasis and hairy leukoplakia in these subjects. These results suggest that HIV-infected patients with oral candidiasis should be carefully monitored for subsequent episodes over the next 12-18 months, and patients with either oral candidiasis or hairy leukoplakia and a low CD4:CD8 cell ratio should be carefully examined for the other type of lesion as well.

Adolescent↗

Oropharyngeal candidiasis in patients with AIDS: randomized comparison of fluconazole versus nystatin oral suspensions.

A total of 167 human immunodeficiency virus (HIV)-infected patients with oropharyngeal candidiasis were randomly assigned to receive 14 days of therapy with liquid suspension fluconazole (100 mg once daily) or liquid nystatin (500,000 U four times daily). At day 14, 87% of the fluconazole-treated patients were clinically cured, as opposed to 52% in the nystatin-treated group (P < .001). Fluconazole eradicated Candida organisms from the oral flora in 60%, vs. a 6% eradication rate with nystatin (P < .001). The fluconazole group had fewer relapses noted on day 28 (18%, vs. 44% in the nystatin group; P < .001). This relapse difference no longer existed by day 42. Fluconazole oral suspension as a systemic therapy was more effective than liquid nystatin as a topical therapy in the treatment of oral candidiasis in HIV-infected patients and provided a longer disease-free interval before relapse.

AIDS-Related Opportunistic Infections↗

Expression of Epstein-Barr virus BMRF-2 and BDLF-3 genes in hairy leukoplakia.

The high level of Epstein-Barr virus (EBV) replication found in hairy leukoplakia (HL) provides a unique opportunity to study EBV expression in the oral epithelium. Screening of a cDNA library from an HL biopsy revealed expression of two genes not previously described in vivo: BMRF-2 and BDLF-3. Sequence analysis of the cDNAs demonstrated several nucleotide changes from the B95-8 sequence. In all six different HL strains studied, only one amino acid change was found in BMRF-2 relative to B95-8 and two amino acid changes were found in the BDLF-3 ORF. mRNA expression of both genes was localized to the lower prickle cell layer of the tongue epithelium. BMRF-2 protein expression was primarily detected in the cell nuclei of the upper prickle cell layer; immunoelectron microscopy revealed that BMRF-2 was associated with the nuclear chromatin. BDLF-3 protein expression was observed in the perinuclear space and cytoplasm of the prickle cells. BDLF-3 has recently been identified as a virion-associated protein, but the functions of BMRF-2 and BDLF-3 have not been elucidated.

DNA, Complementary↗

Epstein-Barr virus BMRF-2 and BDLF-3 expression in hairy leukoplakia.

Hairy leukoplakia (HL) is a lesion found on the side of the tongue of immunocompromised individuals, including those with human immunodeficiency virus (HIV) infection. The lesion has unique histopathologic features and is characterised by high-level Epstein-Barr virus (EBV) replication, multiple EBV strains, and extensive inter- and intra-strain recombination. Expression of EBV genes spanning the entire viral life cycle from latency-associated genes to late, replicative genes has been detected in the lesion. HL thus provides a unique opportunity to study EBV expression in oral epithelium, and to study expression of novel EBV genes. We therefore constructed a cDNA library from an HL biopsy and detected expression of two genes not previously described in vivo: BMRF-2 and BDLF-3. Sequence analysis of the cDNAs revealed few amino acid changes from the B95-8 sequence. Expression of both genes was localized to the lower prickle cell layer of the tongue epithelium. BMRF-2 protein expression was primarily detected in the cell nuclei of the upper prickle cell layer. BDLF-3 protein expression was observed in the peri-nuclear space and Golgi compartment. The function of these proteins is currently under investigation.

AIDS-Related Opportunistic Infections↗

Management of the oral mucosal lesions seen in association with HIV infection.

Oral lesions cause considerable morbidity in association with HIV infection. Their successful management depends upon accurate diagnosis and the use of appropriate therapy. Various treatment approaches are described for some of the common oral lesions including Kaposi's sarcoma, oral candidiasis, hairy leukoplakia and recurrent oral ulcers associated with HIV disease. This paper will discuss the therapies available in the USA and UK. In other countries some of the drugs discussed will be available in different doses and preparations. In addition other drugs may be available in other parts of the world that are not licensed for use in the USA or UK, and their availability may vary.

Antifungal Agents↗

Accidental exposures to blood and body fluids among health care workers in dental teaching clinics: a prospective study.

The authors evaluated accidental exposures to blood and body fluids reported to a hotline or to health officials at four dental teaching clinics. The authors used a standard questionnaire to solicit and record data regarding each exposure. During a 63-month period, 428 parenteral exposures to blood or body fluids were documented. Dental students and dental assistants had the highest rates of exposure. Syringe needle injuries were the most common type of exposure, while giving injections, cleaning instruments after procedures and drilling were the activities most frequently associated with exposures.

Accidents, Occupational↗