The Olfactory Cleft Endoscopy Scale: a multi-institutional validation study in chronic rhinosinusitis.

BACKGROUND: Olfactory dysfunction (OD) associated with chronic rhinosinusitis (CRS) remains quite challenging. Instruments to precisely assess olfactory cleft anatomy and their association with olfaction are needed. METHODS: The olfactory cleft endoscopy scale (OCES) was used to assess the olfactory cleft in healthy control subjects and a cohort of patients with CRS. Psychophysical and psychosocial olfactory function were assessed and correlations with OCES scores were measured. RESULTS: Control subjects and subjects with CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP) were enrol- led. OCES correlated with both psychophysical and psychosocial olfaction, as measured by threshold, discrimination and identi- fication (TDI) scores and Questionnaire on Olfactory Disorders (QOD-NS) scores for all case and control subjects combined. OCES improved in both CRS groups postoperatively with the highest correlation seen in postoperative olfaction in CRSwNP patients. CRS patients who achieve near perfect OCES and sinus endoscopy scores after surgery have olfactory metrics that are indistin- guishable from controls regardless of polyp status. CONCLUSIONS: The OCES is a valid olfactory-specific measure that demonstrates strong validity and provides complimentary infor- mation to traditional sinus endoscopy to aid in our understanding of OD associated with CRS.

A 2-year efficacy study of Not On Tobacco in Florida: an overview of program successes in changing teen smoking behavior.

BACKGROUND: Adolescent smoking has been an issue of major concern in the United States. This has led to a need for the development, evaluation, and dissemination of effective youth cessation programs. The purpose of this paper is to report the results of a 2-year demonstration study (1999-2000) of the American Lung Association's teen smoking cessation program, the Not On Tobacco (NOT) program. METHODS: The study used a "matched" design wherein each NOT school was matched to a brief intervention (BI) school. The study consisted of 20 NOT and 20 BI Florida high schools encompassing 627 students. The primary outcome measures were carbon monoxide-validated quit and reduction rates for NOT and BI schools at 5.2 months postprogram. RESULTS: NOT smoking cessation and reduction outcomes were significantly better than those of the brief intervention. Further, data indicate that NOT was more effective than the brief intervention for females compared with males; males showed successful quit attempts in both intervention groups. Overall, more NOT youth either quit or reduced smoking than did BI youth. CONCLUSIONS: These positive smoking behavior changes suggest that NOT is an effective teen smoking cessation option.

Integrin- and cadherin-mediated induction of the matrix metalloprotease matrilysin in cocultures of malignant oral squamous cell carcinoma cells and dermal fibroblasts.

Matrilysin is a matrix metalloprotease (MMP) overexpressed in a number of cancers including skin, head and neck squamous cell carcinomas, and prostate and colon adenocarcinomas. Matrilysin has been shown to play a role in the degradation of the basement membrane that separates epithelium from stroma allowing tumor cells to intravasate into the bloodstream and metastasize. Here, we show that an oral squamous cell carcinoma cell line (SCC-25) expresses low levels of promatrilysin when cultured alone. However, when SCC-25 cells are cocultured with human foreskin fibroblasts (HFF), there is a 40-fold induction of promatrilysin expression. We tested whether this induction of promatrilysin expression was due to the release of paracrine factors, cell-cell interactions, or cell-matrix interactions. Our results indicate induced promatrilysin expression is the result of both cell-cell and cell-matrix interactions. We demonstrate that beta1 integrins as well as cadherins, specifically N-cadherin and E-cadherin, are involved in the induction of promatrilysin expression. Our results are of general interest in relation to the regulation of MMP expression through cell surface receptor regulation. Further investigation may lead to the identification of novel targets for suppression of invasion and metastasis in oral tumors.

Effect of weight loss on the ECG of normotensive morbidly obese patients.

BACKGROUND: Morbid obesity produces a variety of ECG alterations, including leftward shifts of the P-wave, QRS, and T-wave axes; disproportionately high frequencies of low QRS voltage; left ventricular hypertrophy and left atrial abnormality; and a high frequency of T-wave flattening in the inferior and lateral leads. This study was designed to assess the effects of substantial weight loss on the ECG in morbid obesity. METHODS: We performed a resting 12-lead ECG on 60 normotensive patients (48 women and 12 men; mean +/- SD age, 37 +/- 7 years), whose body weight was twice their ideal body weight prior to and at the time of maximum weight loss after bariatric surgery. RESULTS: Mean weight decreased from 136 +/- 7 to 85 +/- 3 kg. Weight loss produced significant decreases in the frequencies of low QRS voltage; Romhilt-Estes point score > or = 5 points; SV(1) + RV(5) or V(6) > 35 mm; RV(5) or V(6) > 26 mm; RaVL > 11 mm; RaVL > or = 7.5 mm; SaVR > 14 mm; P-terminal force more negative than - 0.04 mm.s in lead V(1); and T-wave flattening in the inferior, lateral, and inferolateral leads. Weight loss significantly shifted the mean P-wave, QRS, T-wave axes rightward, and significantly reduced mean RaVL and mean SaVR voltage. CONCLUSION: Substantial weight loss is capable of reversing many of the ECG alterations associated with morbid obesity.

Statewide demonstration of not on tobacco: a gender-sensitive teen smoking cessation program.

This study represented the largest statewide demonstration (n = 346) of the teen smoking cessation program Not On Tobacco (N-O-T) to date and one of the few systematically controlled teen smoking cessation trials reported in the literature. Results showed that N-O-T female teens were 4 times more likely to quit smoking almost 6 months after the program ended than female teens who received a brief intervention (BI). The quit rate for the N-O-T female groups was significantly higher than that for female brief intervention comparison groups. The study demonstrated that 2 times more N-O-T than BI teens quit smoking overall. Differences in the biochemically validated quit rate between the N-O-T groups and the brief intervention groups overall and for male participants were not statistically different, however. Furthermore, findings showed that N-O-T was more effective than the brief intervention in assisting youth with cigarette reduction. There was a significant difference in the reduction rate between the N-O-T and the BI groups on weekdays and weekends 6 months after the program ended. Overall, approximately 84% of N-O-T teens either quit or reduced smoking, compared with approximately 55% of BI teens. This study is 1 phase of an ongoing multiphase evaluation of N-O-T. This study resulted in several important findings that will help guide future teen cessation studies and tobacco cessation efforts of school health professionals.

Biatrial myxoma resembling an interatrial clot in transit on echocardiogram.

A 47-year-old man had an embolic stroke. Transesophageal echocardiography showed biatrial, elongated, mobile masses that appeared interconnected via a patent foramen ovale. Echocardiography did not distinguish between an interatrial clot in transit and an atypical biatrial myxoma. Surgical resection and subsequent histopathologic examination identified the mass as a biatrial myxoma. This case identifies a limitation of echocardiography in the diagnosis of cardiac myxoma.

The relationship between breast asymmetry, breast size and the occurrence of breast cancer.

Breast cancer is the second most common cancer among women in the world and in developed countries it is the most common. The early identification of women at risk is therefore of great importance and any additional measures which may aid diagnosis, particularly in high risk groups, would be of benefit. Breast volume and breast asymmetry were calculated from mammograms of 250 women with breast cancer and compared with those of 250 age-matched controls. There was evidence that breast cancer patients had more breast asymmetry and larger breasts than age-matched healthy women. The former observation is the first evidence that high breast asymmetry may be a risk factor for breast cancer. Breast asymmetry is likely to be a predictor of, rather than the effect of breast cancer.

Targeting of the rasT24 oncogene to the proximal convoluted tubules in transgenic mice results in hyperplasia and polycystic kidneys.

Five families of transgenic mice were derived from one-cell-stage embryos injected with gamma GT-rasT24, a fusion gene consisting of the gamma-glutamyl transpeptidase (gamma GT) 5' flanking region containing promoter I linked to a mutated (codon 12) human H-ras oncogene. The transgene was expressed selectively in the kidneys, eyes, and brains of all families as determined by reverse transcription-polymerase chain reaction, nuclease protection assays, and in situ hybridization. In two of five families, kidney lesions consisting of proximal tubular hyperplasia, renal cysts, and microadenomas developed in male animals; males also expressed higher levels of gamma GT/rasT24 RNA. Early lesions consisted of proximal tubular hyperplasia as defined by alkaline phosphatase histochemistry, gamma GT immunohistochemistry, and electron microscopy and could be correlated with the presence of rasT24 RNA within the cystic proximal tubular epithelium by in situ hybridization. Advanced lesions also involved other segments of the nephron and consisted of cysts lined by a flattened unicellular layer of attenuated epithelium. No rasT24 could be identified within cystic lesions of the distal nephron and collecting tubules by in situ hybridization, and they most likely arise by external compression. Animals from the two transgenic strains exhibiting cystic lesions die of renal failure beginning at 8 months of age. No difference in cell-cycle parameters or DNA ploidy between transgenic and control kidneys was identified by flow cytometric analysis. No renal carcinomas developed. The primary renal effects of the H-rasT24 oncogene in this model system consist of proximal tubular hyperplasia and polycystic kidneys. This model appears to provide a useful in vivo system for the study of ras oncogene function and control of renal cell proliferation.

Protein kinase C inhibits Ca2+ accumulation in cardiac sarcoplasmic reticulum.

It is now recognized that phorbol esters are negative inotropic agents in mammalian heart which presumably act via stimulation of Ca2(+)-activated phospholipid-dependent protein kinase (PKC). The goal in the present study was to identify the underlying cellular processes. Digitonin-permeabilized cultured neonatal rat ventricular myocytes were used to study biochemical and functional effects of phorbol esters on cardiac sarcoplasmic reticulum (SR). These cells contracted spontaneously at 3 microM Ca2+. Beating was inhibited by 10 microM ryanodine and was insensitive to 1 microM nifedipine. Thus, beating behavior results from the phasic oscillation of Ca2+ transport by SR in this preparation. Phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), decreased frequency by 30%, suggesting that Ca2+ transport by SR had been reduced. Whereas cAMP stimulated the rate of oxalate-supported 45Ca2+ uptake 2-fold, phorbol esters, TPA, and phorbol 12,13-dibutyrate inhibited this process by about 45%. The effects of phorbols were specific: (a) the alpha-analogues of TPA and phorbol 12,13-dibutyrate were inactive; and (b) the phorbol esters had no effect on Ca2+ transport in cells that had been depleted of PKC. TPA decreased oxalate-stimulated Ca2+ uptake over the entire range of Ca2+ concentrations, from 0.1 to 10 microM, by at least 70% without shifting the half-maximal effective Ca2+ concentration. Taken together these results indicate that the effects of phorbol ester on cardiac contraction are due to decreased Ca2+ transport by the SR and that these responses are mediated by PKC. These studies support the interpretation that the negative inotropic effects of phorbol esters are due, in part, to decreased SR function.

Multinucleation in alveolar macrophages from rats treated with chlorphentermine.

When rats were treated with chlorphentermine, a cationic amphiphilic drug, a phospholipid storage disorder developed in alveolar macrophages, the severity of which was directly proportional to the duration of treatment over a 4-week period. Concomitantly, a progressively greater percentage of the cells became multinucleated such that, after 4 weeks of drug treatment, 18 per cent of the cells contained more than one nucleus. Greater than 99 per cent of the macrophages from control rats had on nucleus per cell. Associated with the multinucleation was an increase in the DNA, RNA, and protein content of the macrophages and increases in the RNA to DNA and protein to RNA ratios relative to cells from untreated rats. Centrifugal elutriation was employed as a means to study the multinucleation as a function of increasing cell size. At each of the 4 weekly intervals studied, the percentage of cells with two or more nuclei increased as the cells became larger. An increase in multinucleation was also found in cells of any given size range as the time of treatment increased. Possible mechanisms responsible for the multinucleation phenomenon are discussed.