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Biomedical subjects

S Silverman

Publications and source records attributed to S Silverman.

At least 19 recordsLinked to original sources
PubMed2004

Overexpression of c-met in oral SCC promotes hepatocyte growth factor-induced disruption of cadherin junctions and invasion.

Hepatocyte growth factor (HGF), the ligand for the c-met proto-oncogene product, is a multifunctional protein that enhances tumor cell motility, extracellular matrix invasion, and mitogenic or morphogenic activities of various cell types. In this study we examined the expression of the c-Met receptor in human oral squamous cell carcinoma (SCC) in vivo and in vitro to explore its relationship to tumor progression and invasiveness. Biopsy specimens of human oral SCC were immunohistochemically stained for c-Met. Nearly all primary oral SCC lesions and lymph node metastases consistently showed intense staining for c-Met, whereas normal oral mucosa showed faint to negative staining only on basal cells. In a panel of human oral SCC cell lines, we found a strong correlation between the levels of c-Met expression and the cells' response to HGF in motility and invasion assays. Sensitivity to HGF also correlated with the expression of the c-Met 9-kb mRNA. When the non-invasive HOC-605 cell line, which expresses a low level of c-Met receptor, was transfected with an expression plasmid containing human c-met cDNA, the transfectant cells showed motile and invasive responses to HGF. Immunostaining and immunoprecipitation studies demonstrated that E-cadherin and c-Met were physically associated at SCC cell-cell junctions, suggesting a direct role for c-Met in induction of junctional integrity. Importantly, HGF caused a rapid elevation of unbound beta-catenin, suggesting its availability for nuclear signal transduction and triggering of cell motility and invasiveness. Thus, overexpression of c-Met may facilitate disruption of E-cadherin junctions. Collectively, these results suggest that HGF/c-Met signaling is a common event in oral SCC that may trigger phenotype modulation and enhanced invasion and metastasis.

Blotting, Northern↗
PubMed2002

Ethnic differences in peripheral vascular disease.

The wide variation in the way coronary artery disease (CAD) affects different ethnic groups and the associated risk factor profiles of these groups have been extensively studied, but ethnic differences in the clinical manifestations of peripheral vascular disease (PVD) have been relatively neglected. The aim of the present review is to provide an overview of PVD in different ethnic groups and to explore possible pathophysiological factors accounting for these differences. Atherosclerotic PVD is generally less prevalent in Indo-Asians and Afro-Caribbeans than in caucasians, despite the 'classical' risk factors being as prevalent, if not more so, suggesting the possibility of as yet unidentified risk factors in these groups. Angiographic and microscopic evidence suggests that patients of African or Afro-Caribbean origin suffer from a different pattern of PVD, which primarily affects the distal arteries. In contrast, Indo-Asians tend to suffer from thromboangiitis obliterans (Buerger's disease) far more frequently than other ethnic groups; thus, their arterial disease appears to present much earlier and with greater severity. However, if this sub-category of patient is excluded, they seem to suffer much less from 'simple' atherosclerotic disease than their caucasian counterparts. Despite a higher prevalence of diabetes among Indo-Asians, the prevalence of intermittent claudication is considerably less in this ethnic group.

Adolescent↗
PubMed2001

Benzydamine HCl for prophylaxis of radiation-induced oral mucositis: results from a multicenter, randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Benzydamine was evaluated in patients with head and neck carcinoma for treatment of radiation-induced oral mucositis, a frequent complication of radiation therapy (RT) for which there is no predictable therapy or preventive treatment currently available. METHODS: The safety and efficacy of 0.15% benzydamine oral rinse in preventing or decreasing erythema, ulceration, and pain associated with oral mucositis during RT were evaluated in a randomized, placebo-controlled trial conducted in patients with head and neck carcinoma. Subjects were to rinse with 15 mL for 2 minutes, 4-8 times daily before and during RT, and for 2 weeks after completion of RT; study evaluations were conducted before RT and routinely thereafter up to 3 weeks after RT. RESULTS: During conventional RT, regimens up to cumulative doses of 5000 centigrays (cGy) benzydamine (n = 69) significantly (P = 0.006) reduced erythema and ulceration by approximately 30% compared with the placebo (n = 76); greater than 33% of benzydamine subjects remained ulcer free compared with 18% of placebo subjects (P = 0.037), and benzydamine significantly delayed the use of systemic analgesics compared with placebo (P < 0.05). Benzydamine was not effective in subjects (n = 20) receiving accelerated RT doses (> or = 220 cGy/day). The incidence of adverse events between treatment groups was comparable without significant differences. Early discontinuation because of adverse events occurred in 6% of benzydamine subjects and 5% of placebo subjects, and there was 1 death (related to the primary diagnosis) in a placebo subject. CONCLUSIONS: Benzydamine oral rinse was effective, safe, and well tolerated for prophylactic treatment of radiation-induced oral mucositis.

Adult↗
PubMed2001

Crevicular fluid elastase levels in relation to periodontitis and metabolic control of diabetes.

The purpose of this study was to investigate the associations between gingival crevicular fluid (GCF) elastase levels, clinical measures of periodontal status, and metabolic control of diabetes in insulin dependent (type 1) diabetes (IDDM) and non-insulin dependent (type 2) diabetes (NIDDM) patients. Sixty patients were recruited from the Diabetes Center at the University of California in San Francisco. Thirty subjects were type 1 diabetics and 30 subjects were type 2 diabetics. Metabolic control was evaluated by glycosylatted hemoglobin (HbA1c) levels. Demographic information was obtained using a structured interview with the subjects. Clinical measurements and GCF samples were taken from the mesio-buccal surfaces of 2 premolars and 2 molars from the most diseased sextant. GCF elastase was determined by measurement of p-Nitroanalide resulting from hydrolysis of elastase specific peptide. Crevicular fluid elastase levels were significantly correlated with gingival index, bleeding index, probing depth and attachment level in both type 1 and type 2 diabetes groups (0.01 <p < 0.001). HbA1c levels were not correlated with clinical measurements and GCF elastase. The results suggest that GCF elastase. age and smoking are risk indicators for periodontitis in patients with diabetes mellitus, and periodontal status is not associated with the duration and metabolic control of diabetes.

Adult↗
PubMed2001

Peripheral vascular disease and hypertension: a forgotten association?

Peripheral vascular disease (PVD) is associated with a high cardiovascular morbidity and mortality. Intermittent claudication is the most common symptomatic manifestation of PVD, but is also an important predictor of cardiovascular death, increasing it by three-fold, and increasing all-cause mortality by two to five-fold. Hypertension is a common and important risk factor for vascular disorders, including PVD. Of hypertensives at presentation, about 2-5% have intermittent claudication, with this prevalence increasing with age. Similarly, 35-55% of patients with PVD at presentation also have hypertension. Patients who suffer from hypertension with PVD have a greatly increased risk of myocardial infarction and stroke. Apart from the epidemiological associations, hypertension contributes to the pathogenesis of atherosclerosis, the basic underlying pathological process underlying PVD. Hypertension, in common with PVD, is associated with abnormalities of haemostasis and lipids, leading to an increased atherothrombotic state. Nevertheless, none of the large antihypertensive treatment trials have adequately addressed whether a reduction in blood pressure causes a decrease in PVD incidence. There is therefore an obvious need for such outcome studies, especially since the two conditions are commonly encountered together.

Antihypertensive Agents↗
PubMed2001

Cytokines play an aetiopathogenetic role in fibromyalgia: a hypothesis and pilot study.

OBJECTIVE: To measure soluble factors having a possible role in fibromyalgia (FM) and compare the profiles of patients with recent onset of the syndrome with patients with chronic FM. METHODS: The production of cytokines, cytokine-related molecules, and a CXC chemokine, interleukin (IL)-8, was examined. Fifty-six patients with FM (23 with <2 yr and 33 with >2 yr of symptoms) were compared with age- and sex-matched healthy controls. Cytokines and cytokine-related molecules were measured in sera and in supernatants of peripheral blood mononuclear cells (PBMC) that were incubated with and without lectins and phorbol myristate acetate (PMA). RESULTS: No differences between FMS and controls were found by measuring IL-1beta, IL-2, IL-10, serum IL-2 receptor (sIL-2R), interferon gamma (IFN-gamma), and tumour necrosis factor alpha (TNF-alpha). Levels of IL-1R antibody (IL-1Ra) and IL-8 were significantly higher in sera, and IL-1Ra and IL-6 were significantly higher in stimulated and unstimulated FM PBMC compared with controls. Serum IL-6 levels were comparable to those in controls, but were elevated in supernatants of in vitro-activated PBMC derived from patients with >2 yr of symptoms. In the presence of PMA, there were additional increases in IL-1Ra, IL-8 and IL-6 over control values. CONCLUSIONS: In patients with FM we found increases over time in serum levels and/or PBMC-stimulated activity of soluble factors whose release is stimulated by substance P. Because IL-8 promotes sympathetic pain and IL-6 induces hyperalgesia, fatigue and depression, it is hypothesized that they may play a role in modulating FM symptoms.

Cytokines↗
PubMed2001

Oral lichen planus: patient profile, disease progression and treatment responses.

BACKGROUND: Oral lichen planus, or OLP, is a common mucocutaneous immunological disease. The objective of this study was to describe the patient profile, disease progression and treatment responses. METHODS: The authors conducted a retrospective, descriptive study using information from patient records at a tertiary referral center. The study included 229 patients with OLP who were seen in the oral medicine clinic at the University of California, San Francisco, between September 1996 and August 2000, for the first time or for a follow-up visit. Signs and symptoms at various clinic visits were quantified. Responses to treatment and disease progression were determined by comparing scores with baseline scores. RESULTS: The mean age at onset of the disease was 55 years, and 154 (67 percent) of the patients were female. Symptoms generally correlated directly with the severity of OLP forms, which ranged from reticular to erosive. Corticosteroids were effective in reducing symptoms, healing ulcers and reducing erythema. At last follow-up, 65 percent of the patients had the same type of OLP seen initially or the disease had progressed to a more severe type, while 35 percent of patients had less-severe forms than that seen at the initial visit. Four patients (1.7 percent) developed oral squamous-cell carcinoma during the follow-up period. CONCLUSIONS: OLP is a chronic disease with no known cure. Symptoms can improve with corticosteroids; however, the lack of long-term (that is, lifetime) treatment compliance and the adverse side effects of the drugs limit optimal results. CLINICAL IMPLICATIONS: Patients with OLP should be treated if symptoms are significant. Follow-up--including supervision of medication use and monitoring of side effects, as well as periodic examinations for possible malignant transformation--is necessary.

Administration, Topical↗
PubMed2001

Demographics and occurrence of oral and pharyngeal cancers. The outcomes, the trends, the challenge.

OVERVIEW: This article summarizes current trends in the occurrence of, mortality rates associated with and rates of survival of oral and pharyngeal cancer. METHODS: The author reviewed relevant data and literature on these aspects of oral and pharyngeal cancer, including data from the National Cancer Institute's Surveillance, Epidemiology and End Results program collected from 1973 to 1998. RESULTS: The occurrence of oral and pharyngeal cancer in the United States remains constant, at about 30,000 new cases diagnosed each year. There has been no marked improvement in the five-year survival rates, which remain at about 50 percent, despite advances in surgery and radiation. Detection of early, localized lesions has not improved significantly during the past three decades. There is a minor trend toward a younger age at diagnosis and a slight increase among women. CONCLUSIONS: On the basis of epidemiologic data, it appears that the most important approach to decreasing morbidity and mortality associated with oral cancer is increasing early detection of localized lesions combined with appropriate treatment. Concomitantly, aggressive counseling is vital to prevent use and encourage cessation of tobacco and alcohol use. CLINICAL IMPLICATIONS: Professional and public education about oral and pharyngeal cancer needs to be improved, and clinicians must emphasize the need for and perform routine oral cancer examinations to promote early diagnosis and treatment.

Adult↗
PubMed2001

Asthma outcome changes associated with use of the leukotriene-receptor antagonist zafirlukast.

A new class of asthma drugs modifying the leukotriene pathway was introduced in 1996. The authors investigated outcome changes associated with use of the leukotriene-receptor antagonist zafirlukast. The study group included patients with asthma (12-64 yr), most with mild-to-moderate, persistent asthma, who had at least two zafirlukast prescriptions within 90 days after the start of zafirlukast treatment. Zafirlukast treatment was associated with reductions in occurrence of outpatient visits, emergency department visits, inpatient stays, and prescriptions for short-acting beta-adrenergic agonists in the next six months (all P < .05). A 12-month pre- and post-zafirlukast treatment comparison in a smaller group of patients and a classification of patients into three mutually exclusive outcome groups (increase, decrease, or no change in outcome events) verified the majority of the findings. A cost analysis from a third-party perspective indicated that costs of zafirlukast treatment were more than offset by cost savings associated with the reductions in outcome events.

Adolescent↗
PubMed2001

Oral cancer: a self-assessment quiz.

This article consists of a quiz on oral cancer knowledge. The goals of the quiz are to reinforce known cancer information and present new information. Photographs are used to bring a sense of the practical problems that clinical pathology presents. Also, a number of real-life case situations are presented with their corresponding illustrations so that the readers may use their clinical judgment and experience in choosing an answer.

Adult↗
PubMed2000

A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study. PROOF Study Group.

PURPOSE: We conducted a 5-year, double-blind, randomized, placebo-controlled study to determine whether salmon calcitonin nasal spray reduced the risk of new vertebral fractures in postmenopausal women with osteoporosis. SUBJECTS AND METHODS: A total of 1,255 postmenopausal women with established osteoporosis were randomly assigned to receive salmon calcitonin nasal spray (100, 200, or 400 IU) or placebo daily. All participants received elemental calcium (1,000 mg) and vitamin D (400 IU) daily. Vertebral fractures were assessed with lateral radiographs of the spine. The primary efficacy endpoint was the risk of new vertebral fractures in the salmon calcitonin nasal spray 200-IU group compared with the placebo group. RESULTS: During 5 years, 1,108 participants had at least one follow-up radiograph. A total of 783 women completed 3 years of treatment, and 511 completed 5 years. The 200-IU dose of salmon calcitonin nasal spray significantly reduced the risk of new vertebral fractures by 33% compared with placebo [200 IU: 51 of 287, placebo: 70 of 270, relative risk (RR) = 0.67, 95% confidence interval (CI): 0.47- to 0.97, P = 0.03]. In the 817 women with one to five prevalent vertebral fractures at enrollment, the risk was reduced by 36% (RR = 0.64, 95% CI: 0.43- to 0.96, P = 0.03). The reductions in vertebral fractures in the 100-IU (RR = 0.85, 95% CI: 0.60- to 1.21) and the 400-IU (RR = 0.84, 95% CI: 0.59- to 1.18) groups were not significantly different from placebo. Lumbar spine bone mineral density increased significantly from baseline (1% to 1. 5%, P<0.01) in all active treatment groups. Bone turnover was inhibited, as shown by suppression of serum type-I collagen cross-linked telopeptide (C-telopeptide) by 12% in the 200-IU group (P <0.01) and by 14% in the 400-IU group (P<0.01) as compared with placebo. CONCLUSION: Salmon calcitonin nasal spray at a dose of 200 IU daily significantly reduces the risk of new vertebral fractures in postmenopausal women with osteoporosis.

Aged↗
PubMed2000

Trends in oral cancer rates in the United States, 1973-1996.

OBJECTIVES: To explore changes in demographic distribution, incidence and survival rates of oral cancer in the United States from 1973 through 1996. METHODS: From the Surveillance, Epidemiology, and End Results (SEER) data, we computed the proportion of oral cancer by demographic characteristics, site, and stage at diagnosis for 1973-84 and 1985-96. We estimated incidence and 5-year relative survival rates of oral cancer by age, gender, and race/ethnicity, and compared survival rates between the two periods. The estimated annual percent change (EAPC) was used to explore trends in incidence rate from 1973 through 1996. RESULTS: Most of the tongue and floor of mouth cancers (>54%) reported during 1973-84 and 1985-96 had spread to a distant site at time of diagnosis. The age-adjusted annual incidence rates of oral cancer decreased among white men from 1973 through 1996, but increased among black men aged 65-69 years, and among young white men (aged 30-34 years) and women (aged 25-29 years). These changes in trend were all statistically significant (testing EAPC=0 at the 0.05 level). Overall, there was no improvement in the 5-year relative survival rate of either whites or blacks with oral cancer. CONCLUSION: There was little change in early detection of oral cancer or in 5-year relative survival rates between 1973-84 and 1985-96 in nine SEER regions. This suggests a deficiency in professional and public education regarding early diagnosis of oral cancer. Furthermore, the increasing trend of oral cancer among older black men and among younger whites merits further investigation.

Adult↗
PubMed2000

Parental perceptions of children's communicative development at stuttering onset.

There has been clinical speculation that parents of young stuttering children have expectations of their children's communication abilities that are not well-matched to the children's actual skills. We appraised the language abilities of 15 children close to the onset of stuttering symptoms and 15 age-, sex-, and SES-matched fluent children using an array of standardized tests and spontaneous language sample measures. Parents concurrently completed two parent-report measures of the children's communicative development. Results indicated generally depressed performance on all child speech and language measures by the children who stutter. Parent report was closely attuned to child performance for the stuttering children; parents of nonstuttering children were less accurate in their predictions of children's communicative performance. Implications for clinical advisement to parents of stuttering children are discussed.

Child Language↗
PubMed2000

Proliferative verrucous leukoplakia of the gingiva.

OBJECTIVE: The purpose of this study was to describe the clinical-pathologic features of what appears to be a gingival form of proliferative verrucous leukoplakia. STUDY DESIGN: Ten adult patients with recurrent and histologically progressive gingival leukoplakias who were diagnosed and treated at the University of California, San Francisco between 1994 and 1999, comprised the subject group for this investigation. Clinical and microscopic features were reviewed. Proliferation indices and p53 expression were evaluated immunohistochemically, and the presence of human papillomavirus (HPV) DNA was determined by using polymerase chain reaction (PCR) amplification. RESULTS: Lesions presented as solitary or regional flat/papillary/verrucal leukoplakias of the free and attached gingiva (tooth-bearing areas only). With time, flat lesions developed a papillary or verruciform profile. Although lesions were recurrent, they were confined to the gingiva, and multiple lesions did not develop. Half the patients used tobacco, and HPV could not be detected by using PCR. Microscopically, 6 cases began as hyperkeratotic lesions, and 4 initially exhibited a psoriasiform pattern with a marked inflammatory component. With recurrences, the lesions became progressively atypical histologically. The proliferation indices for these lesions showed modest increases over normal epithelium, and positive p53 staining was evident in 4 of 10 cases, indicating a disruption of the keratinocyte cell cycle in these lesions. The mechanism associated with the positive p53 staining (protein binding to wild type p53 versus mutation of the p53 gene) was not determined. Lesions recurred after conservative scalpel or laser excision, and many developed into verrucous or squamous cell carcinoma. CONCLUSIONS: Proliferative verrucous leukoplakia of the gingiva (PVLG) appears to be a subset of oral proliferative verrucous leukoplakia. It can be characterized as a solitary, recurring, progressive white patch that develops a verruciform architecture and may not be associated with HPV. PVLG has an unpredictable course and is at risk for development into verrucous or squamous cell carcinoma. Currently, there is no way to determine or predict which gingival white lesions will follow the clinical course described for this group of patients with PVLG.

Aged↗