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J C Stern

Publications and source records attributed to J C Stern.

13 recordsLinked to original sources

Elucidation of CYP2E1 5' regulatory RsaI/Pstl allelic variants and their role in risk for oral cancer.

The CYP2E1 gene, whose protein product plays an important role in the metabolism of various carcinogens, exhibits two polymorphisms recognized by the restriction enzymes RsaI and PstI in its transcriptional regulatory region that have been previously implicated in cancer susceptibility. In this study, we have examined these polymorphisms to elucidate CYP2E1 allelic haplotype, examining the prevalence of these CYP2E1 alleles in Caucasians and African Americans and their potential role in risk for oral cancer. In addition to the c1 (RsaI[+]/PstI[-]) and c2 (RsaI[-]/PstI[+]) alleles reported in previous studies, we have identified two new alleles, c3 (RsaI[+]/PstI[+]) and c4 (RsaI[-]/PstI[-]). The prevalence of the c2 and c3 alleles differs between racial groups, with African Americans exhibiting a lower prevalence of the c2 allele (0.003) but a higher prevalence of the c3 allele (0.049) than Caucasians (0.031 for c2 and 0.004 for c3). Of the 570 subjects screened in this study, the c4 allele was observed in one subject, a Caucasian case with the (c4/c4) genotype. A significant increase in the CYP2E1 (c1/c1) genotype was observed in oral cancer cases as compared to frequency-matched controls in subjects who smoked < or =24 pack-years (P=0.033). No association was observed between CYP2E1 genotype and risk for oral cancer in the heavy-smoking group (i.e. > 24 pack-years). Similar trends were observed for both Caucasians and African Americans. These data suggest that the c1 allele may contribute to increased risk for oral cancer.

Adult↗

Comparison of GSTM polymorphisms and risk for oral cancer between African-Americans and Caucasians.

Two members of the mu class of glutathione S-transferase (GST) genes, GSTM1 and GSTM3, have polymorphic alleles which have been associated with altered levels of GST mu protein expression and may be linked to increased risk for several tobacco-related cancers. Oral cancer is a tobacco-related disease that affects African-American men at a significantly higher incidence than Caucasian men. To examine the potential role of GSTM polymorphisms in risk for oral cancer in African-Americans and Caucasians, the prevalences of the GSTM1 null and GSTM3 intron 6 polymorphisms were examined in 63 African-American and 101 Caucasian patients with histologically confirmed primary oral cancer, as well as in 133 African-American and 213 Caucasian matched control subjects. In African-Americans, the odds ratio for oral cancer associated with the GSTM1 (0/0) genotype was 3.1 [95% confidence interval (CI) = 1.1-8.5], with the association between the GSTM1 (0/0) genotype and oral cancer risk strongest in heavy smokers [i.e. > 24 pack-years; odds ratio (OR) = 5.4, 95% CI = 1.2-24]. Using the potentially most protective GSTM1 [+]/GSTM3 (B/B) genotype as the reference group, increased risk for oral cancer was observed in African-Americans with the GSTM1 [+]/GSTM3 [(A/A) + (A/B)] (OR = 2.2, 95% CI = 0.82-6.0), GSTM1 (0/0)/GSTM3 (B/B) (OR = 4.3, 95% CI = 1.1-16), and GSTM1 (0/0)/GSTM3 [(A/A) + (A/B)] (OR = 6.6, 95% CI = 1.2-38) genotypes (P < 0.01, trend test). No significant associations were observed between GSTM genotype and oral cancer risk in Caucasians. These results suggest that the GSTM1 null and GSTM3 intron 6 polymorphisms play an important role in risk for oral cancer among African-Americans and implicates the mu class of GSTs as important tobacco carcinogen detoxifying enzymes in this population.

Female↗

Association between glutathione S-transferase pi genetic polymorphisms and oral cancer risk.

Polymorphisms in the gene encoding the glutathione S-transferase (GST) pi metabolizing enzyme have previously been associated with susceptibility to various cancers. In this study, the importance of GSTP1 genotypes as determinants of risk for oral cancer was assessed by examining the prevalence of GSTP1 alleles in 157 incident oral cancer cases and 260 non-cancer control individuals frequency-matched by race, sex, and age at diagnosis (+/- 5 years). The GSTP1*A, GSTP1*B, GSTP1*C, and GSTP1*D alleles were elucidated by polymerase chain reaction-restriction fragment length polymorphism analysis of polymorphisms present in codons 105 (isoleucine:valine) and 114 (alanine:valine) of the GSTP1 gene. Increased risk for oral cancer was observed in individuals who were homozygous for any combination of GSTP1 polymorphic alleles (i.e. *B, *C, and/or *D alleles; odds ratio = 2.4, 95% confidence interval = 1.2-4.8). Similar risk was observed in both Caucasians (odds ratio = 2.6, 95% confidence interval = 1.1-6.2) and African-Americans (odds ratio = 2.3, 95% CI = 0.68-7.5). A greater risk was observed in individuals with the GSTP1 (Var/Var) genotype who were exposed to low levels of smoking (i.e. < or = 20 pack-years [py], odds ratio = 3.4, 95% confidence interval = 1.1-11) than among heavier smokers (i.e. > 20 pack-years [py], odds ratio = 1.4, 95% confidence interval = 0.48-4.0). These results suggest that GSTP1 genotype may play a role in risk for oral cancer particularly among lighter smokers.

Black or African American↗

p53, but not p16 mutations in oral squamous cell carcinomas are associated with specific CYP1A1 and GSTM1 polymorphic genotypes and patient tobacco use.

Inactivation of tumor suppressor genes like p53 and p16 play a key role in tumor progression, with a high incidence of mutations existing for both genes in oral squamous cell carcinomas. Previous studies have demonstrated, (i) a correlation between the prevalence of p53 mutations and tobacco use [Brennan et al. (1995) New Engl. J. Med., 332, 712-717; Lazarus et al. (1996) Carcinogenesis, 17, 733-739], and (ii) a link between genotypes in specific xenobiotic metabolizing enzymes and oral cancer susceptibility [Park et al. (1997) Cancer Epid. Biomarkers Prev., 6, 791-797). In this paper, we present results of our examination of a series of 80 oral squamous cell carcinomas for p53 exons 5-9 and p16 exons 1-2 mutations, and the potential association of these mutations with specific genotyping patterns. p53 mutation prevalence in oral tumors was linked with increased patient tobacco use using several stratification criteria. There was a significantly higher prevalence of p53 mutations in OCSCCs from patients who smoked > 30 pack-years as compared to tumors from patients who smoked < or = 30 pack-years (OR = 2.8; CI = 1.1-7.2). No significant association was observed with patient alcohol consumption. There was a significant association between the prevalence of p53 mutations in oral tumors and CYP1A1 genotyping patterns in these oral cancer patients, with the highest p53 mutation prevalence observed in subjects with the CYP1A1 [val]/GSTM1 [+] genotype (OR = 6.0; CI = 1.2-29.7). A significant association was not observed between the prevalence of p16 mutations in oral tumors and tobacco use, or CYP1A1 [val] or GSTM1 (0/0) genotypes. These data suggest that the induction of mutations in specific tumor suppressor genes or oncogenes in oral tumors may be associated with specific carcinogen exposures, and that this association may be linked to specific polymorphic genotypes in xenobiotic-metabolizing enzyme genes.

Benzo(a)pyrene↗

A cadaveric study of the motor nerves to the levator scapulae muscle.

Understanding the surgical anatomic relationships of the motor nerves to the levator scapulae muscle is imperative for reducing postoperative shoulder dysfunction in patients undergoing neck dissection. To elucidate this relevant anatomy, cervical (C3, C4) and brachial (C5 via dorsal scapular nerve) plexi contributions to the levator scapulae were assessed with respect to posterior triangle landmarks in 37 human cadaveric necks. An average of approximately 2 (actual 1.92) nerves from the cervical plexus (range 1 to 4 nerves) emerged from beneath the posterior border of the sternocleidomastoid muscle in a cephalad to caudad progression to enter the posterior triangle of the neck on their way to innervating the levator scapulae. These cervical plexus contributions exhibited a fairly regular relationship to the emergence of cranial nerve XI and the punctum nervosum along the posterior border of the sternocleidomastoid muscle. After emerging from the posterior border of the sternocleidomastoid to enter the posterior triangle of the neck, cervical plexus contributions to the levator scapulae traveled for a variable distance posteriorly and inferiorly, sometimes branching or coming together. Ultimately these nerves crossed the anterior border of the levator scapulae as 1 to 3 nerves (average 1.94) in a regular superior to inferior progression. The dorsal scapular nerve from the brachial plexus exhibited highly variable anatomic relations in the inferior aspect of the posterior triangle, and was found to penetrate or give branches to the levator scapulae in only 11 of 35 neck specimens. We have found that the levator scapulae receives predictable motor supply from the cervical plexus. Our data elucidate surgical anatomy useful to head and neck surgeons.

Aged↗

CYP1A1 and GSTM1 polymorphisms and oral cancer risk.

The importance of both the CYP1A1 exon 7 (ile:val) and GSTM1 (0/0) polymorphisms in oral cancer susceptibility was assessed by examining polymorphic prevalences in 135 patients with oral cancer and 135 noncancer controls frequency-matched by age at diagnosis (+/- 5 years), race, sex, and institute of patient recruitment. The prevalence of the GSTM1 (0/0) genotype was approximately 51% in both cases and controls. The prevalence of the CYP1A1 (ile:val) polymorphism [including both the (ile/val) and (val/val) genotypes] was significantly higher in cases as compared to controls (17.6% versus 7.6%, respectively; crude odds ratio, 2.6; confidence interval, 1.2-5.7). No association was observed between polymorphic prevalence and levels of smoking or alcohol consumption in cases. These results suggest that the GSTM1 null genotype is not associated with oral cancer risk. These results also suggest that individuals with the CYP1A1 exon 7 ile:val polymorphism are at increased risk for oral cancer, and that this risk may not be influenced by differences in exposure to tobacco smoke.

Adult↗

Comparison of surgery and radiotherapy in T1 and T2 glottic carcinomas.

We retrospectively studied 356 patients who received treatment for T1 and T2 glottic carcinomas. Two hundred and thirty patients were treated with surgery (200 by cordectomy, 15 by vertical partial laryngectomy, and 15 by subtotal laryngectomy). Radiotherapy was used to treat 126 patients. There were 206 T1 and 24 T2 lesions in the surgically treated group and 107 T1 and 19 T2 lesions in the radiotherapy group. Sixty-four patients received radiotherapy because it was the treatment of choice (scheduled radiotherapy) and 62 patients received radiotherapy because they had medical contraindications for surgery (default radiotherapy). Actuarial survival rates at 5 years were 84% for patients who underwent surgery and 78% for patients who underwent scheduled radiotherapy. In the surgically treated group, there were 10 local recurrences in 170 patients with tumors of the true vocal cord, eight recurrences in 36 patients with anterior commissure lesions, and 6 recurrences in 24 patients with tumors extending to the arytenoid. In the scheduled radiotherapy group, there were 7 local recurrences in 38 patients with true vocal cord tumors, 6 recurrences in 20 patients with anterior commissure tumors, and 5 recurrences in 6 patients with tumors extending to the arytenoid. We conclude that survival is similar in these patients whether they receive operative treatment or scheduled radiotherapy. However, in the radiotherapy group, local recurrences were more frequent in patients with tumors extending to the arytenoid. We advocate extended functional surgery for patients with T1 and T2 glottic lesions except for those with small tumors arising from the middle third of the vocal cord.

Carcinoma, Squamous Cell↗

Benign nasopharyngeal masses and human immunodeficiency virus infection.

Manifestations of the acquired immunodeficiency syndrome are common in the head and neck and are becoming well known to the otolaryngologist. We present a series of seven patients who complained of nasal obstruction and hearing loss and were found, on examination, to have large obstructing nasopharyngeal masses and otitis media with effusion. Biopsy revealed benign lymphoid proliferation. Because of a suspicion of human immunodeficiency virus infection by history, antibody titers were obtained and were found to be positive in all cases. With the known increased rate of aggressive extranodal B-cell lymphomas in human immunodeficiency virus-infected patients, its existence in the nasopharynx should be ruled out histologically in symptomatic patients. Nasal obstruction and hearing loss secondary to nasopharyngeal lymphoid proliferation in high-risk patients can be an early sign of human immunodeficiency virus infection. Patients presenting with this clinical entity should be advised to have serologic testing and further treatment and counseling if necessary.

Adult↗

Head and neck manifestations of the acquired immunodeficiency syndrome in children.

The head-and-neck manifestations of HIV infection in children are very different from those in the adult population. Recurrent bacterial and viral infections are common manifestations, and persistent sinusitis or otitis media should make the otolaryngologist suspicious of HIV infection if the child has been exposed to the virus. Other common problems include mucocutaneous and esophageal candidiasis, recurrent herpes I and II and zoster infections, parotid swelling, and cervical lymphadeopathy.

Acquired Immunodeficiency Syndrome↗

Carbon dioxide laser excision of earlobe keloids. A prospective study and critical analysis of existing data.

When steroid injections have failed, the most common approach for the treatment of earlobe keloids is surgical excision. The carbon dioxide laser has recently been used with varying reported success in the treatment of keloids and hypertrophic scars. Proponents of this technique claim that the intrinsic properties of laser surgery, which slows fibroblast proliferation, may be responsible for delaying or preventing the recurrence of keloids. We report results on the effectiveness of carbon dioxide laser excision of earlobe keloids. Eighteen patients were followed up from 8 months to 2 years, or up to a recurrence. Four patients within this group with bilateral keloids provided a self-controlled sample. One ear was randomly chosen for laser excision and the other for scalpel excision. There were recurrences in both groups. There were also 17 recurrences in a group of 23 keloids excised by laser, 9 occurring between 6 and 12 months postoperatively. We failed to demonstrate a lower recurrence rate of earlobe keloids using the carbon dioxide laser and discuss some of the factors responsible for this outcome.

Adolescent↗

In vitro effectiveness of 13 agents in otomycosis and review of the literature.

Many agents have been recommended for treating otomycosis, but no preparation has been widely accepted. To compare the effectiveness of many recommended preparations, we performed an in vitro study using 15 species of fungi and yeast cultured from patients presenting with otomycosis during the past year. By measuring zones of inhibition, we assessed the effectiveness of aqueous Merthiolate, Burow's solution (2%), VoSol HC, VoSol plain, Cortisporin suspension, clotrimazole 1%, Mycostatin, amphotericin B, ethanol 95%, miconazole, tolnaftate 1%, natamycin, and flucytosine. Most otic preparations showed little or no growth inhibition. However, Merthiolate was very effective against all organisms tested, clotrimazole was very effective against most yeast and fungi tested, and nystatin had the widest spectrum of activity among the antifungals. Tolnaftate was ineffective. Vigorous cleaning of the external auditory canal remains the mainstay in treating otymycosis, but proper laboratory identification and suitable topical therapy are also important in dealing with this capricious infection.

Antifungal Agents↗

Otomycosis.

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Ear Diseases↗