Clinical safety of enamel matrix derivative (EMDOGAIN®) in the treatment of periodontal defects

Abstract The aim of the present clinical trial was to test tolerability during 2 treatments with EMDOGAIN® in a large number of patients. An open, controlled study design in 10 Swedish specialist clinics was chosen, with a test group of 107 patients treated with EMDOGAIN® in connection with periodontal surgery at 2 surgical test sites per patient. The procedures were performed 2 to 6 weeks apart on one-rooted teeth with at least 4 mm deep intraosseous lesions. A control group of 33 patients underwent flap surgery without EMDOGAIN® at I comparable site. In total 214 test and 33 control surgeries were performed. Serum samples were obtained from test patients for analysis of total and specific antibody levels. 10 of the patients had samples taken before and after the first surgery. 56 other samples were taken after one treatment with EMDOGAIN®, and 63 after 2 treatments. None of the samples, not even from allergy-prone patients after 2 treatments, indicated deviations from established baseline ranges. This indicates that the immunogenic potential of EMDOGAIN® is extremely low when applied in conjunction with periodontal surgery. Comparison between the test and control groups demonstrated the same type and frequency of post-surgical experiences, i.e., reactions caused by the surgical procedure itself. Clinical probing and radiographic evaluation was performed at baseline and 8 months postsurgery. About half of the patients (44 test and 21 control) were also evaluated after 3 years. There was a significant difference between the test and control results at 8 months post surgery. and this difference had increased further at the 3 year follow-up. The 2.5–3 mm increase in attachment and bone level after treatment with EMDOGAIN® was of the same magnitude as seen in the studies with split-mouth design aiming for lest of effectiveness of EMDOGAIN®.     

The effect of comonomer composition, silane heating, and filler type on aqueous TEGDMA leachability in model resin composites

Experimental composites using either bisGMA/TEGDMA or UEDMA/ TEGDMA matrices, quartz or barium glass fillers, and 2 different filler silanization methods were evaluated regarding monomer leachability in distilled water. The leached amount was detected and quantified using gas chromatography. The results showed that twice as much TEGDMA is leached from a bisGMA/TEGDMA based composite than from an UEDMA/ TEGDMA based composite, when both contain 50 wt% TEGDMA. The hypothesis suggested that the higher degree of cure of UEDMA/TEGDMA based composites would be reflected in a lower monomer leaching value, and this hypothesis was supported by the findings. Whether such a correlation exists within groups of UEDMA/TEGDMA based matrices having different degrees of cure was not determined and needs to be investigated in future studies. Variables such as filler composition and silane treatment did not affect the leaching values of TEGDMA in water. That finding suggests that future studies should target differences in matrices, and that the need for considering effects of filler composition and silane treatment methods should not receive the same priority.     

Characterization of a novel breast carcinoma xenograft and cell line derived from a BRCA1 germ-line mutation carrier

A human tumor xenograft (L56Br-X1) was established from a breast cancer axillary lymph node metastasis of a 53-year-old woman with a BRCA1 germ-line nonsense mutation (1806C>T; Q563X), and a cell line (L56Br-C1) was subsequently derived from the xenograft. The xenograft carries only the mutant BRCA1 allele and expresses mutant BRCA1 mRNA but no BRCA1 protein as determined by immunoprecipitation or Western blotting. The primary tumor, lymph node metastasis, and xenograft were hypodiploid by DNA flow cytometry, whereas the cell line displayed an aneuploidy apparently developed via polyploidization. Cytogenetic analysis, spectral karyotyping, and comparative genomic hybridization of the cell line revealed a highly complex karyotype with numerous unbalanced translocations. The xenograft and cell line had retained a somatic TP53 missense mutation (S215I) originating from the primary tumors, as well as a lack of immunohistochemically detectable expression of steroid hormone receptors, epidermal growth factor receptor, human epidermal growth factor receptor 2 (HER-2), and keratin 8. Global gene expression analysis by cDNA microarrays supported a correlation between the expression profiles of the primary tumor, lymph node metastasis, xenograft, and cell line. We conclude that L56Br-X1 and L56Br-C1 are useful model systems for studies of the pathogenesis and new therapeutic modalities of BRCA1-induced human breast cancer.     

Erholungsfähigkeit der Niere nach zwei- oder dreistündiger Ischämie und Resektion der gesunden Niere,kontrolliert während einer neunmonatigen Erholungszeit

Zusammenfassung Die linke Kaninchenniere wurde einer ischämischen Belastung von 2 oder 3 Std ausgesetzt und die rechte Niere 21 Tage nach der Belastung entfernt. Während einer neunmonatigen Erholungszeit bestimmten wir im Katheterharn Gefrierpunktsdepression, Eiweiß, Glucose, Harnstoff, Ammoniak, Natrium, Kalium, Chlor und im Plasma den Rest-N. Das Experiment wurde durch einen Konzentrierungsversuch abgeschlossen und die Nieren nach Tötung der Tiere histologisch untersucht.Die Nierenfunktion erholt sich in wenigen Tagen nach der Resektion der gesunden Niere vollständig ohne Ausfälle von Einzelfunktionen. Gefrierpunktsdepression und Konzentrierungsversuch zeigen eine fast normale Anpassungsbreite der belasteten Nieren. Es kommt in keinem Fall zur Retention harnpflichtiger Substanzen. Anzeichen für die Ausbildung einer Schrumpfniere sind nicht vorhanden.Die histologische Untersuchung der Nieren zeigt bis auf den Ausfall einzelner Nephrone einen nahezu normalen Befund. Die Erholung der Nierenzellen ist morphologisch und funktionell vollständig, obwohl der Schwund an RNS bei gleicher Belastung 40–45% beträgt.Außer der für die Niere früher festgestellten Unabhängigkeit der Erholungsfähigkeit von der anaeroben Glykolyse übersteht der Informationsbestand der Niere unter Erhaltung des Bauplans ebenfalls einen absoluten Sauerstoffmangel von 3 Std ohne Schaden.Mit 3 TextabbildungenDer Deutschen Forschungsgemeinschaft danken wir für großzügige Förderung unserer Untersuchungen.Auszugsweise vorgetragen auf der 28. Tagung der Deutschen Physiologischen Gesellschaft, Juni 1963 in Köln.     

Natural history of oral papillomavirus infections in spouses: a prospective Finnish HPV Family Study.

BACKGROUND: The natural history of genital human papillomavirus infection is well known, but nearly nothing is known about the outcome of oral HPV-infection. OBJECTIVES AND STUDY DESIGN: To study natural history of oral HPV in spouses during the follow-up 331 women (mean 25.5+/-3.4 years) and 131 men (mean 28.8+/-5.0 years) were recruited from maternity unit. Scrapings from healthy oral mucosa of spouses at baseline, 2, 6, 12 and 24 months and genital samples were taken for HPV testing. HPV DNA was detected by nested PCR and confirmed by hybridization using a cocktail of 12 high-risk (HR) oligoprobes. RESULTS: The detection rate of HR HPVs varied from 15% to 27%. Baseline oral HPV status between the spouses was closely related (odds ratio 4.3; 95% confidence interval 1.6-12.0; P=0.006). Persistent oral infection in one spouse was a significant risk factor (odds ratio 10.0; 95% confidence interval 1.5-68.7; P=0.005) for oral HR HPV persistence in the other partner. Cumulative incidence of new HR HPV infections was identical in both spouses, while men seemed to clear their infection more rapidly. In univariate survival analysis, the partner's oral or genital HPV status, oral sex habits or age did not predict clearance or acquisition of oral HR HPV. CONCLUSION: Natural history of HPV infection in oral mucosa mimics that of genital HPV infection. Oral sex had no association to oral HPV infection, but a persistent oral HPV infection of the spouse increased the risk of persistent oral HPV infection 10-fold in the other spouse.     

Rare SP-A alleles and the SP-A1-6A(4) allele associate with risk for lung carcinoma

Next to cigarette smoking, genetic factors may contribute to lung cancer risk. Pulmonary surfactant components may mediate response to inhaled carcinogenic substances and/or play a role in lung function and inflammation. We studied associations between surfactant protein (SP) genetic variants and risk in lung cancer subgroups. Samples (n=308) were genotyped for SP-A1, -A2, -B, and -D marker alleles. These included 99 patients with small cell lung carcinoma (SCLC, n=31), or non-SCLC (NSCLC, n=68) consisting of squamous cell carcinoma (SCC, n=35), and adenocarcinoma (AC) (n=23); controls (n=99) matched by age, sex, and smoking status (clinical control) to SCLC and NSCLC; and 110 healthy individuals (population control). We found (a) no significant marker associations with SCLC, (b) rare SP-A2 (1A9) and SP-A1 (6A11) alleles associate with NSCLC risk when compared with population control, (c) the same alleles (1A9, 6A11) associate with risk for AC when compared with population (6A11) or clinical control (1A9), and (d) the SP-A1-6A4 allele (found in approximately 10% of the population) associates with SCC, when compared with population or clinical control. A correlation between SP-A variants and lung cancer susceptibility appears to exist, indicating that SP-A alleles may be useful markers of lung cancer risk.     

Combined chemotherapy-radiotherapy study of small cell bronchial carcinoma: chemo-/radiotherapy vs radio-/chemotherapy

The authors studied the effect of a chemo-/radiotherapy or radio-/chemotherapy on 52 cases of microcellular bronchial carcinoma, classification "limited disease". The survival curves were slightly better for the patients submitted to primary chemotherapy, but the difference was not statistically significant, and the curves coincided again after 18 months. 60 to 80% of the patients had no complaints or only unimportant complaints during more than half of their survival time. In 23 patients with "extensive disease" who received only a symptomatic therapy or a combined palliative chemotherapy, chemotherapy had a slightly better effect, but this was not statistically significant.     

Sleep-apnea in patients with end-stage renal disease and objective results

BACKGROUND: A high prevalence of sleep apnea syndrome (SAS) of 54%-80% has been reported in patients with end-stage renal disease (ESRD). However, these studies were either done in highly selected small patient groups or without objective data using questionnaires only. PATIENTS AND METHODS: We, therefore, studied the prevalence of SAS in a large, unselected group of patients with ESRD. During a 6-month period 77 out of 84 unselected patients with ESRD filled out the sleep apnea questionnaire of the University of Marburg and the Epworth Sleepiness Scale. In 55 of these patients, snoring sounds, heart rate, body position and transcapillary arterial oxygen saturation were recorded with an ambulatory device during the night after hemodialysis. RESULTS: In the questionnaires, 70.3% of the patients reported of an excessive day-time sleepiness, 40.5% of unwillingly falling asleep during the daytime and 35.2% rated their ability to concentrate as decreased. 30.9% (40% male/15% female) of the patients showed evidence of sleep-disordered breathing with an apnea-hypopnea-index (AHI) equal or more than 5/hour. 16.4% (20% male/10% female) of the patients met the diagnostic criteria of SAS. Neither dialysis and biochemical data nor anamnestic parameters measured by the questionnaires correlated significantly with sleep-disordered breathing. CONCLUSION: The prevalence of SAS in this large unselected patient group was not as high as previously reported, but it is still considerably higher than in the general population. Objective recordings are essential, as questionnaires overestimate the prevalence of SAS in patients with ESRD. As SAS promotes hypertension and impairs quality of life, ESRD patients might benefit from a treatment of concomitant SAS.     

p53Mutations and Presence of HPV DNA Do Not Correlate with Radiosensitivity of Gynecological Cancer Cell Lines

Objective.The correlation betweenp53tumor suppressor gene mutations and the presence of high-risk human papillomavirus (HPV) DNA with thein vitroradiosensitivity of gynecological malignancies was studied in 26 cell lines derived from gynecological cancers of 23 patients.Methods.Comparison of the intrinsic radiosensitivity was performed with mean inactivation dose (D?) determined with the 96-well plate clonogenic assay.p53mutations were investigated with polymerase chain reaction and single-strand conformation polymorphism (PCR–SSCP) analysis and direct DNA sequencing, and the presence of HPV DNA was studied with PCR using HPV consensus primers.Results. p53mutations were found in 6 of 10 vulvar squamous cell carcinoma (SCC) lines. Nine vulvar and 1 vaginal SCC cell lines were HPV DNA negative and 1 vulvar cell line was HPV 16 positive. All 4 cervical SCC lines were HPV positive and possessed the wild-typep53.Three cell lines expressed HPV 16 and 1 HPV 68. Among 10 endometrial cancer cell lines, 2 cell lines with mutantp53and 1 HPV 16 positive cell line were found. No correlation could be demonstrated between inactivation of thep53gene and radiosensitivityin vitro;the cell lines were evaluated as one group or according to their anatomical origin or histology.Conclusion.Our results indicate that inactivation of thep53gene through mutation or binding with HPV DNA does not increase the resistance of gynecological malignancies to ionizing radiationin vitro.