Tongue abscess induced by embedded remnant fishbone.

The authors reported a 56-year-old man with progressive pain over left bottom of oral cavity involving tongue for 3 days. He had a puncture history of tongue by fishbone, which was immediately removed 3 weeks ago. The subsequent contrast-enhanced computed tomography scan of neck disclosed an abscess formation with a faint linear radiopaque material inside, consisting with remnant fishbone retention. The patient was treated conservatively with intravenous antibiotics, followed by an uneventful course during subsequent follow-up for more than 9 months until now. Tongue abscess is a rare but potentially life threatening clinical entity. Foreign body puncture-related tongue abscess should be listed as a differential diagnosis in cases with acute tongue swelling.

Selective estrogen receptor-beta (SERM-beta) compounds modulate raphe nuclei tryptophan hydroxylase-1 (TPH-1) mRNA expression and cause antidepressant-like effects in the forced swim test.

Estrogen acts through two molecularly distinct receptors termed estrogen receptor alpha (ERα) and estrogen receptor beta (ERß) which bind estradiol with similar affinities and mediate the effects of estrogen throughout the body. ERα plays a major role in reproductive physiology and behavior, and mediates classic estrogen signaling in such tissues as the uterus, mammary gland, and skeleton. ERß, however, modulates estrogen signaling in the ovary, the immune system, prostate, gastrointestinal tract, and hypothalamus, and there is some evidence that ERß can regulate ERα activity. Moreover, ERß knockout studies and receptor distribution analyses in the CNS suggest that this receptor may play a role in the modulation of mood and cognition. In recent years several ERß-specific compounds (selective estrogen receptor beta modulators; SERM-beta) have become available, and research suggests potential utility of these compounds in menopausal symptom relief, breast cancer prevention, diseases that have an inflammatory component, osteoporosis, cardiovascular disease, and inflammatory bowel disease, as well as modulation of mood, and anxiety. Here we demonstrate an antidepressant-like effect obtained using two SERM-beta compounds, SERM-beta1 and SERM-beta2. These compounds exhibit full agonist activity at ERß in a cell based estrogen response element (ERE) transactivation assay. SERM-beta1 and 2 are non-proliferative with respect to breast as determined using the MCF-7 breast cancer cell-based assay and non-proliferative in the uterus as determined by assessing the effects of SERM-beta compounds on immature rat uterine weight and murine uterine weight. In vivo SERM-beta1 and 2 are brain penetrant and display dose dependent efficacy in the murine dorsal raphe assays for induction of tryptophan hydroxylase mRNA and progesterone receptor protein. These compounds show activity in the murine forced swim test and promote hippocampal neurogenesis acutely in rats. Taken together these data suggest that ERß may play an important role in modulating mood and the ERß specific compounds described herein will be useful tools for probing the utility of an ERß agonist for treating neuroendocrine-related mood disturbance and menopausal symptoms.

Multicenter randomized clinical trial of donepezil for memory impairment in multiple sclerosis.

OBJECTIVES: The goal of this study was to determine if memory would be improved by donepezil as compared to placebo in a multicenter, double-blind, randomized clinical trial (RCT). METHODS: Donepezil 10 mg daily was compared to placebo to treat memory impairment. Eligibility criteria included the following: age 18-59 years, clinically definite multiple sclerosis (MS), and performance ≤ ½ SD below published norms on the Rey Auditory Verbal Learning Test (RAVLT). Neuropsychological assessments were performed at baseline and 24 weeks. Primary outcomes were change on the Selective Reminding Test (SRT) of verbal memory and the participant's impression of memory change. Secondary outcomes included changes on other neuropsychological tests and the evaluating clinician's impression of memory change. RESULTS: A total of 120 participants were enrolled and randomized to either donepezil or placebo. No significant treatment effects were found between groups on either primary outcome of memory or any secondary cognitive outcomes. A trend was noted for the clinician's impression of memory change in favor of donepezil (37.7%) vs placebo (23.7%) (p = 0.097). No serious or unanticipated adverse events attributed to study medication developed. CONCLUSIONS: Donepezil did not improve memory as compared to placebo on either of the primary outcomes in this study. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence which does not support the hypothesis that 10 mg of donepezil daily for 24 weeks is superior to placebo in improving cognition as measured by the SRT in people with MS whose baseline RAVLT score was 0.5 SD or more below average.

Cortactin overexpression in the esophageal squamous cell carcinoma and its involvement in the carcinogenesis.

The aim of this study is to examine whether dysregulated expression of cortactin occurs in esophageal squamous cell carcinoma (ESCC) and is involved in the development of ESCCs. An immunohistochemistry study for cortactin expression was performed on 46 pairs of surgically resected non-tumor and ESCC tumor tissues and murine tumors of esophagi induced by a carcinogen. The results show increased cortactin expression in 20 and in 22 to a lesser extent, out of a total 46 ESCC tumor tissues. Increased cortactin was also detected in the premalignant lesions, the early stage dysplasia and carcinoma in situ, of ESCC tumor tissues. Differential polymerase chain reaction results showed slight increases in the EMS1 gene only in two of 10 ESCC tumor tissues, suggesting that EMS1 gene amplification is not the only mechanism for cortactin overexpression. In the mouse model induced by treatment with 4-nitroquinoline 1-oxide and arecoline, increased cortactin was detected in the epithelia with hyperkeratosis, papillomas, and ESCCs with invasion into the submucosa, respectively. Overall, we observed cortactin overexpression in early and late stages of human ESCCs and carcinogen-induced murine ESCCs, suggesting a role for cortactin in esophageal carcinogenesis.

Glucocorticoid modulation of tryptophan hydroxylase-2 protein in raphe nuclei and 5-hydroxytryptophan concentrations in frontal cortex of C57/Bl6 mice.

Considerable attention has focused on regulation of central tryptophan hydroxylase (TPH) activity and protein expression. At the time of these earlier studies, it was thought that there was a single central TPH isoform. However, with the recent identification of TPH2, it becomes important to distinguish between regulatory effects on the protein expression and activity of the two isoforms. We have generated a TPH2-specific polyclonal antiserum (TPH2-6361) to study regulation of TPH2 at the protein level and to examine the distribution of TPH2 expression in rodent and human brain. TPH2 immunoreactivity (IR) was detected throughout the raphe nuclei, in lateral hypothalamic nuclei and in the pineal body of rodent and human brain. In addition, a prominent TPH2-IR fiber network was found in the human median eminence. We recently reported that glucocorticoid treatment of C57/Bl6 mice for 4 days markedly decreased TPH2 messenger RNA levels in the raphe nuclei, whereas TPH1 mRNA was unaffected. The glucocorticoid-elicited inhibition of TPH2 gene expression was blocked by co-administration of the glucocorticoid receptor antagonist mifepristone (RU-486). Using TPH2-6361, we have extended these findings to show a dose-dependent decrease in raphe TPH2 protein levels in response to 4 days of treatment with dexamethasone; this effect was blocked by co-administration of mifepristone. Moreover, the glucocorticoid-elicited inhibition of TPH2 was functionally significant: serotonin synthesis was significantly reduced in the frontal cortex of glucocorticoid-treated mice, an effect that was blocked by mifepristone co-administration. This study provides further evidence for the glucocorticoid regulation of serotonin biosynthesis via inhibition of TPH2 expression, and suggest that elevated glucocorticoid levels may be relevant to the etiology of psychiatric diseases, such as depression, where hypothalamic-pituitary-adrenal axis dysregulation has been documented.

Prevalence of bacterial and fungal agents causing lower respiratory tract infections in patients with human immunodeficiency virus infection.

PURPOSE: This study was designed to document the prevalence of HIV associated respiratory infections in Hyderabad. Such studies have not been worked out before in this region. METHODS: The study included specimens from 130 patients with complaints suggestive of lower respiratory tract infection. Among them 100 were HIV reactive and 30 were HIV nonreactive. Both the expectorated as well as induced sputum samples were collected and processed to examine for the bacterial and fungal pathogens including Pneumocystis carinii. RESULTS: Sputum samples from 63% of HIV reactive and 33.3% of HIV nonreactive patients were culture positive. In all, there were 70 pathogens isolated from the HIV reactive subjects, 44.3% were bacteria, 42.9% were Mycobacteria and 12.8 % were fungi. CONCLUSIONS: Lower respiratory tract infection is a common problem among HIV reactive patients and majority are bacterial infections. Polymicrobial isolation was observed only among the HIV reactive patients. PCP was not documented in our series.

Correlation between voice handicap index and voice laboratory measurements in dysphonic patients.

Factors underlying voice disorders can be categorized into three distinct domains: emotional, physical, and functional. The Voice Handicap Index (VHI) subjectively evaluates voice disorders in terms of these three factors. On the other hand, Voice Laboratory Measurements (VLM) use objective criteria to evaluate the severity of voice disorders. Use of these two different tests (VHI and VLM) on dysphonic patients has, however, tended to yield results that vary widely in their conclusions. This report reviewed 135 testing sessions on dysphonia patients. Seventy-nine of the tests were VHI, and 56 were VLM. All VHI and VLM parameters were entered into a statistical program and analyzed using a Pearson correlation. The results show that each VHI parameter provides a significant level of reliability (P < 0.01) when compared with other VHI parameters. Four VLM parameters also demonstrated significant reliability (P < 0.01) in comparison with other VLM parameters. However, when comparing across testing methods, VHI and VLM parameter reliability is shown to be poor (P > 0.05). With such a large discrepancy between the results of VHI and VLM testing, no objective parameter can yet be regarded as a definitive prognostic factor in a subjective evaluation of dysphonic patients.

[A comparative study of temperament and maternal rearing pattern in preschoolers with congenital heart disease and preschoolers generally].

The purposes of this study were: (1) to understand the differences in temperamental characteristics between preschoolers with congenital heart disease (CHD) and preschoolers generally, and (2) to discuss the relationship between characteristics of children temperament and maternal rearing patterns. The research subjects based on convenience sampling were 61 preschoolers with CHD and 76 non-CHD preschoolers. The "children temperament questionnaire" and "maternal rearing pattern rating scale" were posed to the mothers of the subjects and were filled in by them. The results showed that mothers of children with mild heart symptoms tended to adopt more protective rearing patterns than mothers of non-CHD children. Children in the group "whole heart function without symptoms" scored higher points for activity than children in the non-CHD group. Preschoolers with mild heart symptoms had greater intensity of reaction and persistence than non-CHD preschoolers, but statistically, there were no significant differences in other temperament characteristics between preschoolers with and without CHD. These results could serve as reference for nursing care of children with CHD and maternal rearing practice.

Prevalence and clustering of cardiovascular risk factors among healthy adults in a Chinese population: the MJ Health Screening Center Study in Taiwan.

OBJECTIVE: To gain insight into the prevalence and clustering of multiple cardiovascular risk factors in a healthy Chinese adult population in Taiwan. DESIGN: A cross-sectional study was carried out in 1996. SUBJECTS: A total of 46,603 subjects (23,485 men and 23,118 women) who were aged 20--59 y and attended a private health screening center for health examination of their own volition. MEASUREMENTS: Multiple cardiovascular risk factors including cigarette smoking, overweight (23 kg/m(2)< or =body mass index (BMI)<25 kg/m(2)) and obesity (BMI> or =25 kg/m(2)), lipid disorder (a ratio of total cholesterol level to the level of high density lipoprotein cholesterol>5 or use of lipid-lowering drugs), hypertension (systolic blood pressure> or =140 mmHg or diastolic blood pressure> or =90 mmHg or use of anti-hypertensive medications), and diabetes mellitus (fasting serum plasma glucose level> or =126 mg/dl or use of anti-diabetic medications) were determined. RESULTS: In comparison to women, men had a higher prevalence of current smoking (42.1 vs 5.6%), overweight (25.1 vs 17.1%) and obesity (33.1 vs 21.5%), lipid disorder (45.1 vs 19.6%), hypertension (17.4 vs 13.2%), as well as diabetes mellitus (4.1 vs 3.4%). The prevalence of men or women having two or more of the cardiovascular risk factors of interest was 54.3 and 21.7%, respectively. With advancing age, the prevalence of risk factors became greater for both genders. More importantly, the clustering of risk factors increased monotonically with increasing BMI levels for men and women. CONCLUSIONS: The prevalence and clustering of cardiovascular risk factors are commonplace in this healthy Chinese adult population. Considering the significant association between clustering of risk factors under study and BMI levels, this study gives an indication that population-based multifactorial interventions may work out favorably for specific groups.

Joint effects of alcohol consumption and cigarette smoking on atherogenic lipid and lipoprotein profiles: results from a study of Chinese male population in Taiwan.

BACKGROUND: The present study examines the effect of joint exposure to cigarette smoking and alcohol intake on serum levels of total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and triglyceride (TG) among Chinese male adults in Taiwan. METHODS: A sample of 3311 men aged 20-59 years who reported having stable smoking and drinking behaviors during the period between January 1995 and December 1996 was selected from a periodic health checkup population. Serum lipids and lipoprotein cholesterol fractions were measured on fasting blood samples taken from participants. Statistical methods of analysis of variance and analysis of covariance were conducted to examine the associations of different smoking-drinking behavioral patterns with lipid and lipoprotein levels. RESULTS: In the observed population, the percentages of men who had stable cigarette smoking and alcohol consumption behaviors were 39.5% (1,307/3,311) and 27.0% (895/3,311), respectively. Mean values of TC and TG increased significantly and monotonically with increasing levels of cigarette smoking and alcohol consumption. In addition, alcohol intake was significantly associated with increased HDL-C and reduced LDL-C levels in a dose-dependent manner. More interestingly, the effect of alcohol consumption on LDL-C (negative) and TG (positive) levels was substantially greater for heavy smoker (>20 cigarettes/day) than for light smokers (< or = 20 cigarettes/day) and non-smokers, while alcohol intake exerted a strong positive influence on HDL-C concentration regardless of levels of cigarette smoking. CONCLUSIONS: In this Chinese male population, cigarette smoking and alcohol consumption were confirmed to have similar effects on lipid and lipoprotein levels as in Caucasians. More interestingly, a significance of joint exposure to smoking and drinking in predicting lipid and lipoprotein levels was evident. These data indicate the importance of multifactorial interventions to obtain more favorable lipid and lipoprotein levels in the population.

Factors related to quality of life in breast cancer patients receiving chemotherapy.

This descriptive correlation study investigated the relationship among individual characteristics, disease characteristics, psychological factors (anxiety, depression, self-esteem), social support, and quality of life in patients with breast cancer receiving chemotherapy. One hundred and fifty women from nine Taipei area hospitals were surveyed with a structured questionnaire. The total quality of life index for breast cancer patients was about average (M = 19.88). The family factor scored highest for importance and satisfaction with quality of life. Patients showed the most dissatisfaction with the health factor. Of the individual characteristics affecting patient quality of life, number of children and social status were statistically significant (p < .05). Of the disease characteristics, the stage of the disease, the commencement of chemotherapy, and the number of chemotherapy treatments were statistically significant (p < .05). The psychological factors were significantly related to patients' quality of life (p < .05). Social support of both relatives and health professionals was significantly related to patients' quality of life (p < .01). Of the four independent variables (individual characteristics, disease characteristics, psychological factors and social support), the most influential factor affecting breast cancer patients' total quality of life was the psychological factor of self-esteem (p < .001). The findings can assist nurses to plan and improve the quality of breast cancer care in terms of understanding the factors affecting patients' quality of life.

D-cbl, a negative regulator of the Egfr pathway, is required for dorsoventral patterning in Drosophila oogenesis.

During Drosophila oogenesis, asymmetrically localized Gurken activates the EGF receptor (Egfr) and determines dorsal follicle cell fates. Using a mosaic follicle cell system we have identified a mutation in the D-cbl gene which causes hyperactivation of the Egfr pathway. Cbl proteins are known to downregulate activated receptors. We find that the abnormal Egfr activation is ligand dependent. Our results show that the precise regulation of Egfr activity necessary to establish different follicle cell fates requires two levels of control. The localized ligand Gurken activates Egfr to different levels in different follicle cells. In addition, Egfr activity has to be repressed through the activity of D-cbl to ensure the absence of signaling in the ventral most follicle cells.

Attenuating the growth of tumors by intratumoral administration of DNA encoding Pseudomonas exotoxin via cationic liposomes.

A gene therapy approach was taken to inhibit tumor growth by transfecting tumor cells with a plasmid encoding a truncated but active form of Pseudomonas exotoxin A (PE), using cationic lipids as the transfection reagent. Cells transfected with this plasmid express PE intracellularly and undergo apoptosis. Transfection was optimized in vitro using two cationic lipids, DOGS and DOSPER. A ratio of between 1:4 and 1:10 (wt/wt) was found to be optimal for DOSPER, and the ratio 1:4 was used for the in vivo study when a smaller injection volume was desired. Estimating the activity of the PE-encoding plasmid was done both directly, by counting cells in vitro after transfection, and by using a cytotoxicity assay, and indirectly, by cotransfecting the plasmid with a plasmid carrying a reporter beta-galactosidase gene and observing a reduction in beta-galactosidase activity with increasing amounts of the PE-encoding plasmid. The cotransfection method was found to be very sensitive, and showed transfection of cells even with 1-2 ng of the PE-encoding plasmid per 10(5) cells. Complexes of the PE-encoding plasmid together with cationic lipid were injected into tumor xenografts in athymic nude mice. The tumor growth of transfected tumors was attenuated compared with control untreated tumors or tumors transfected with a nontoxin-expressing vector. These results indicate the potential of such a treatment for attenuating solid tumor growth in vivo.

Blood alcohol concentration among injured drivers in Hualien County.

Vehicle-related injuries are the major cause of death and injuries in Hualien County. Driving under the influence of alcohol plays a major role in such crashes. From December 1997 to May 1998, we determined the blood alcohol concentrations of 750 injured drivers from vehicle crashes, visiting the two emergency rooms of teaching hospitals in Hualien. The objectives of this study were to investigate the incidence of alcohol used in vehicle crashes, to identify the prevalence groups for prevention and to discuss alcohol testing at emergency services. Sixty-four percent were male; 27.5% were aborigines. The mean age was 36.5 +/- 16.5 years. About 54.1% tested positive for blood alcohol concentration (BAC), which ranged from 13 to 611 mg/dL; 38.6% had BAC levels exceeding 50 mg/dL and 21.1% exceeding 200 mg/dL. The mean BAC was 85.9 mg/dL (+/- 118.5). Middle-aged males and aborigines were more likely to drive under the influence of alcohol. We recommend blood alcohol testing to be mandatory at the emergency service and to be used as evidence for prosecution in a court of law. Preventing drunk driving through community programs is imperative, especially in the aboriginal communities.

Roles of the C terminus of Armadillo in Wingless signaling in Drosophila.

Drosophila melanogaster Armadillo and its vertebrate homolog beta-catenin play multiple roles during development. Both are components of cell-cell adherens junctions and both transduce Wingless (Wg)/Wnt intercellular signals. The current model for Wingless signaling proposes that Armadillo binds the DNA-binding protein dTCF, forming a bipartite transcription factor that activates Wingless-responsive genes. In this model, Armadillo's C-terminal domain is proposed to serve an essential role as a transcriptional activation domain. In Xenopus, however, overexpression of C-terminally truncated beta-catenin activates Wnt signaling, suggesting that the C-terminal domain might not be essential. We reexamined the function of Armadillo's C terminus in Wingless signaling. We found that C-terminally truncated mutant Armadillo has a deficit in Wg-signaling activity, even when corrected for reduced protein levels. However, we also found that Armadillo proteins lacking all or part of the C terminus retain some signaling ability if overexpressed, and that mutants lacking different portions of the C-terminal domain differ in their level of signaling ability. Finally, we found that the C terminus plays a role in Armadillo protein stability in response to Wingless signal and that the C-terminal domain can physically interact with the Arm repeat region. These data suggest that the C-terminal domain plays a complex role in Wingless signaling and that Armadillo recruits the transcriptional machinery via multiple contact sites, which act in an additive fashion.

Prospective anthropometric analysis of sagittal orbital-globe relationship following fronto-orbital advancement in childhood.

Fronto-orbital advancement is a common procedure for correction of supraorbital retrusion in patients with coronal craniosynostosis. The aim of this study was two-fold: to quantitate change in the sagittal orbital-globe relationship following fronto-orbital advancement in childhood and to determine the ratio of skeletal-to-soft tissue movement. Soft-tissue points on the orbital rim, orbitale superius (os), orbitale laterale (ol), orbitale inferius (oi), and nasion (n), referenced to apex corneae (ac), were measured preoperatively and postoperatively by a custom-made anthropometer. Intraoperative bony advancement was measured with a caliper. Patients were selected with uniform advancement at the fronto-nasal suture and laterally at the mortise and tenon. Fifteen patients with syndromic craniosynostosis were included in the study (six male, nine female): Apert (n = 2), Crouzon (n = 5), Pfeiffer (n = 4), Saethre-Chotzen (n = 3), and Boston type (n = 1). Average age at operation was 8.7 years (range, 4.5 to 10.5 years). Age, sex, method of fixation, postoperative interval, diagnosis, and skeletal movement were analyzed for possible effect on the magnitude of soft-tissue advancement. Average intraoperative skeletal advancement was 12.1 mm, and average postoperative soft-tissue movement was 10.3 mm (p < 0.001), measured at the midpoint of the supraorbital rims (os). The soft tissue: skeletal movement ratio was 0.9:1. Os was the only point at which soft-tissue advancement could be predicted (Spearman's rank correlation coefficient = 0.67); soft-tissue changes at ol, oi, and n were unpredictable. Skeletal movement was the only determinant of soft-tissue advancement of all variables tested, i.e., diagnosis, age, sex, previous fronto-orbital advancement, and wire versus plate fixation. We make recommendations for calculating the magnitude of fronto-orbital advancement, based on preoperative anthropometry and a soft-to-hard tissue advancement factor.

COL9A3: A third locus for multiple epiphyseal dysplasia.

Multiple epiphyseal dysplasia (MED), an autosomal dominant osteochondrodysplasia, is a clinically and genetically heterogeneous disorder characterized by mild short stature and early-onset osteoarthritis. The phenotypic spectrum includes the mild Ribbing type, the more severe Fairbank type, and some unclassified forms. Linkage studies have identified two loci for MED. One of these, EDM1, is on chromosome 19, in a region that contains the cartilage oligomeric matrix protein (COMP) gene. Mutations have been identified in this gene in patients with the Ribbing type, the Fairbank type, and unclassified forms of MED. The second locus, EDM2, maps to chromosome 1, in a region spanning COL9A2. Recently, a splice-site mutation was found in COL9A2, causing skipping of exon 3 in one family with MED. Because of the exclusion of the EDM1 and EDM2 loci in some families, the existence of a third locus has been postulated. We report here one family with MED, evaluated clinically and radiologically and tested for linkage with candidate genes, including COMP, COL9A1, COL9A2, and COL9A3. No linkage was found with COMP, COL9A1, or COL9A2, but an inheritance pattern consistent with linkage was observed with COL9A3. Mutation analysis of COL9A3 identified an A-->T transversion in the acceptor splice site of intron 2 in affected family members. The mutation led to skipping of exon 3 and an in-frame deletion of 12 amino acid residues in the COL3 domain of the alpha3(IX) chain and thus appeared to be similar to that reported for COL9A2. This is the first disease-causing mutation identified in COL9A3. Our results also show that COL9A3, located on chromosome 20, is a third locus for MED.

Membrane-tethered Drosophila Armadillo cannot transduce Wingless signal on its own.

Drosophila Armadillo and its vertebrate homolog beta-catenin are key effectors of Wingless/Wnt signaling. In the current model, Wingless/Wnt signal stabilizes Armadillo/beta-catenin, which then accumulates in nuclei and binds TCF/LEF family proteins, forming bipartite transcription factors which activate transcription of Wingless/Wnt responsive genes. This model was recently challenged. Overexpression in Xenopus of membrane-tethered beta-catenin or its paralog plakoglobin activates Wnt signaling, suggesting that nuclear localization of Armadillo/beta-catenin is not essential for signaling. Tethered plakoglobin or beta-catenin might signal on their own or might act indirectly by elevating levels of endogenous beta-catenin. We tested these hypotheses in Drosophila by removing endogenous Armadillo. We generated a series of mutant Armadillo proteins with altered intracellular localizations, and expressed these in wild-type and armadillo mutant backgrounds. We found that membrane-tethered Armadillo cannot signal on its own; however it can function in adherens junctions. We also created mutant forms of Armadillo carrying heterologous nuclear localization or nuclear export signals. Although these signals alter the subcellular localization of Arm when overexpressed in Xenopus, in Drosophila they have little effect on localization and only subtle effects on signaling. This supports a model in which Armadillo's nuclear localization is key for signaling, but in which Armadillo intracellular localization is controlled by the availability and affinity of its binding partners.

Tamoxifen and fenretinide in women with metastatic breast cancer.

BACKGROUND: Tamoxifen and fenretinide combination therapy has been shown to be an active treatment regimen in metastatic breast cancer patients. This pilot study sought to determine whether the addition of fenretinide to tamoxifen would be associated with antitumor activity in metastatic breast cancer patients who had been previously treated with tamoxifen or who had hormone receptor negative disease. The effect of this therapy on circulating plasma transforming growth factor-beta (TGF-beta) levels and serum lipids was also examined. PATIENTS AND METHODS: Thirty-one patients were treated with tamoxifen (20 mg p.o. daily), and fenretinide (400 mg p.o. daily with a 3-day drug holiday each month). Plasma TGF-beta testing was performed using isoform specific sandwich ELISA. RESULTS: Twenty four of the 31 patients were evaluable for an antitumor response including 14 estrogen receptor (ER) positive patients who had failed prior tamoxifen therapy, seven ER-negative patients, and three hormone therapy naive ER-positive patients. There were no objective antitumor responses; three patients had stable disease for 8, 8, and 24 months. Five patients (16%) discontinued therapy for toxicity (one for grade 3 skin rash and four for abnormal dark adaptation). There was a statistically significant decrease in total cholesterol (median change per patient of -13.5 mg/dl; p = 0.049, a 6.5% decrease), and an increase in HDL levels (median change per patient of +18 mg/dl, p = 0.0001, a 35% increase) with tamoxifen and fenretinide therapy. TGF-beta1 plasma levels were normal in 26 of 28 patients, and no changes in these levels post-treatment were demonstrated. CONCLUSIONS: Tamoxifen and fenretinide therapy is not an active combination in ER negative metastatic breast cancer or in patients whose disease has progressed on tamoxifen. This combination had a beneficial effect on total serum cholesterol and HDL levels with no associated rise in serum triglyceride levels. The 400 mg dose of fenretinide was associated with symptomatic nyctalopia in one-third of patients making it an unsuitable dose for use in breast cancer prevention studies.

Correlation of serum IgA rheumatoid factor levels with disease severity in rheumatoid arthritis.

In the present study, the IgA rheumatoid factor (IgA RF) was assayed by ELISA in 114 sera of patients with active RA. IgA RF was found in the sera of 38 (33.3%) patients. A total of 56 disease variables were studied, differences in variables between IgA RF positive and negative patients were analyzed. The presence of IgA RF was found to be associated with a rapid progressive course, RA activity, onset of extra-articular manifestations (especially systemic rheumatoid vasculitis), high IgM RF titres, circulating immune complexes, cryoglobulins, and C-reactive protein levels. There was no statistically significant difference in serum IgA levels between IgA RF seropositive and seronegative patients. The presence of IgA RF showed a positive correlation with the level of IgM RF. The results of this study showed that the determination of IgA RF has a practical use in the establishment of the severe course of RA with systemic damages.