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®.     

Mechanical function of intermediate filaments in arteries of different size examined using desmin deficient mice

Protein composition and mechanical function of intermediate filaments were examined in arteries of different sizes using desmin deficient mice (Des−/−) and their wild-type controls (Des+/+). Using SDS-PAGE gels and Western blots we found a gradient in desmin expression in the arterial tree; the desmin content increased from the elastic artery aorta, via the muscular mesenteric artery to the resistance-sized mesenteric microarteries ∼150 μm in diameter in Des+/+ mice. Mechanical experiments were performed on the aorta, the mesenteric artery and resistance-sized arteries using wire myographs. For aorta and mesenteric artery, no differences in passive or active circumference- stress relations were found between Des−/− and Des+/+ mice. In microarteries, both passive and active stress were lower in the Des−/− group. In conclusion, large elastic and muscular arteries contain a relatively low amount of desmin, and the desmin intermediate filaments do not seem to play a major role in the mechanical properties of these larger arterial vessels. In the microarteries, where expression of desmin is high, desmin plays a role in supporting both passive and active tension.     

Helicase Hmi1 stimulates the synthesis of concatemeric mitochondrial DNA molecules in yeast Saccharomyces cerevisiae

Hmi1p is a helicase in the yeast Saccharomyces cerevisiae required for maintenance of the wild-type mitochondrial genome. Disruption of the HMI1 ORF generates ^– and ⁰ cells. Here we demonstrate that, in ^– yeast strains, Hmi1p stimulates the synthesis of long concatemeric mitochondrial DNA molecules associated with a reduction in the number of nucleoids used for mitochondrial DNA packaging. Surprisingly, the ATPase negative mutants of Hmi1p can also stimulate the synthesis of long concatemeric ^– mitochondrial DNA molecules and support the maintenance of the wild-type mitochondrial genome, albeit with reduced efficiency. We show that, in the mutant hmi1–5 background, the wild-type mitochondrial DNA is fragmented; and we propose that, in hmi1 yeast cells, the loss of the wild-type mitochondrial genome is caused by this fragmentation of the mitochondrial DNA.     

BRAF and NRAS Mutations Are Frequent in Nodular Melanoma but Are not Associated with Tumor Cell Proliferation or Patient Survival

Previous studies have shown frequent mutations in the BRAF (V-raf murine sarcoma viral oncogene homolog B1) or NRAS (neuroblastoma RAS viral [V-ras] oncogene homolog) genes in cutaneous melanoma, but the relationship between these alterations and tumor cell proliferation has not been examined in human melanoma. In our study of 51 primary nodular melanomas and 18 paired metastases, we found mutations in BRAF (codon 600, previously denoted 599) in 15 primary tumors (29%) and eight metastases (44%). The figures for NRAS mutations were 27% and 22%, respectively. Mutations in BRAF and NRAS genes were mutually exclusive in all but one case, and were maintained from primary tumors through their metastases. Mutations, however, were not associated with tumor cell proliferation by Ki-67 expression, tumor thickness, microvessel density, or vascular invasion, and there were no differences in patient survival. Although BRAF and NRAS mutations are likely to be important for the initiation and maintenance of some melanomas, other factors might be more significant for proliferation and prognosis in subgroups of aggressive melanoma.     

Cholesteryl ester storage disease of clinical and genetic characterisation: A case report and review of literature

BACKGROUND Cholesteryl ester storage disease(CESD)is a rare genetic disease.Its symptoms and severity are highly variable.CESD is a systemic disease that can lead to the accumulation of fat and inflammation in the liver,as well as gastrointestinal and cardiovascular disease.The majority of patients require liver transplantation due to decompensated cirrhosis.Enzyme replacement therapy has been approved based on a randomized trial.Our study aims to clinically and genetically evaluate two siblings with CESD who underwent liver transplantation,as well as their first-degree family members.CASE SUMMARY The siblings were compound heterozygous for the missense variant in LIPA exon 8,c.894G>A,(p.Gln298Gln)and a single base pair deletion,c.482del(p.Asn161Ilefs*19).Analyses of single nucleotide polymorphisms showed variants with an increased risk of fatty liver disease and fibrosis for both patients.Clinically,both patients show signs of recurrence of CESD in the liver after transplantation and additional gastrointestinal and cardiovascular signs of CESD.Three family members who were LIPA heterozygous had a lysosomal acid lipase activity below the reference value.One of these carriers,a seven-year-old boy,was found to have severe dyslipidemia and was subsequently treated with statins.CONCLUSION Our study underlines that CESD is a multi-organ disease,the progression of which may occur post-liver transplantation.Our findings underline the need for monitoring of complications and assessment of possible further treatment.     

Adverse reactions in healthy and immunocompromised children under six years of age vaccinated with the Danish BCG vaccine, strain Copenhagen 1331: implications for the vaccination policy in Sweden

A retrospective analysis of the adverse reactions reported between 1979 and 1991, in the 139000 children under six years of age vaccinated in Sweden with the Danish BCG vaccine, strain Copenhagen 1331, showed an incidence of I.9 per 1000 vaccinated children. Regional lymphoglandular swellings and/or abscesses were most commonly reported in 1.4 per 1000. Serious, disseminated, BCG infections developed in four infants vaccinated neonatally. Three of the infants suffered from severe, combined, immunodeficiency syndrome, undiagnosed at the time of vaccination. The incidence of severe, combined, immunodeficiency syndrome was higher in the BCG-vaccinated population (4 per 100000 infants vaccinated within a year of their births), compared with all newborns in Sweden (1 per 100 000). The mean age at the onset of symptoms was 2.4 months for the seven non-BCG-vaccinated infants versus 1.3 months for the four BCG-vaccinated ones, while the immunodeficiency syndrome was diagnosed at an average age of 7.6 months in those who were not vaccinatedversus 5.3 months in those BCG-vaccinated. It is recommended that the selective BCG vaccination of infants at high risk of exposure to tuberculosis should be postponed to six months of age to reduce the risk of inoculating infants suffering from immunodeficiency syndromes.     

Immunocytochemical detection of the carbohydrate antigen, Sialyl Lewisx, in normal human skin and during irritant contact dermatitis

Abstract Sialys Lewis^x (SLex) is a ligand for the E-selectin and the interaction of E-selectin on the endothelium and SLe^x on T cells may be important for T-cell migration into the skin. We investigated the expression of SLe^x on Langerhans cells (LC) in normal skin and on LC repopulating epidermis deprived of LC due to a preceding irritant contact dermatitis. SLe^x was visualized by fluorescence and light microscopic immunocytochemistry using the monoclonal antibody. CSLEX-1. The results showed that about 40% of LC in normal epidermis express SLe^x. In the repopulation phase, most of the epidermal cells were CDla⁺/SLe^x+. We suggest that SLe^x is present on epidermal LC that have recently immigrated from the dermis.     

Extracochlear eight-channel electrode system

The Cologne-Düren research group has developed a new extracochlear eight-channel electrode system. The first observations on six cases have shown encouraging psychoacoustic results.     

CARDIOVASCULAR EFFECTS OF BETA-RECEPTOR BLOCKING DRUGS DURING HALOTHANE ANAESTHESIA IN MAN

Fifteen patients anaesthetized with halothane were given a beta-adrenergic receptor blocking substance intravenously, either propranolol or l-alprenolol.
The drugs usually induced an insignificant drop in blood pressure, a slight bradycardia, and a small reduction in cardiac output in patients not subjected to concomitant surgery. In one patient, the reaction was more pronounced. The immediate administration of atropine seemed to restore the circulatory state.
Nine patients were subjected to surgery during the administration of the beta-blocking agents. Pronounced hypotension resulted in seven of them. This effect was observed both after propranolol and l-alprenolol. Again, atropine reversed the hypotension.
These observations suggest that the administration of beta-adrenergic receptor blocking agents during anaesthesia should be limited by very strict indications, and be used under carefully controlled conditions.

ZUSAMMENFASSUNG

15 mit Halothan narkotisierte Patienten erhielten i.v. einen Beta-Rezep-torenblocker, und zwar entweder Propanolol oder 1-Alprenolol.
Diese Mittel fiihrten in der Regel zu einem nicht-signifikanten Blutdruck-abfall, zu einer geringgradigen Bradykardie und einer leichten Verminderung des Herzminutenvolumens bei Patienten, die nicht gleichzeitig operiert wurden. Bei einem Patienten war die Reaktion dramatischer. Die sofortige Gabe von Atropin schien den Kreislaufzustand wieder zu normalisieren.
Neun Patienten erhielten Betablocker wahrend einer Operation. Bei sieben von ihnen kam es zu ausgepragten Blutdruckabfall. Diese Wirkung wurde sowohl nach Propranolol als auch nach 1-Alprenolol beobachtet.
Diese Beobachtungen geben Grund zur Empfehlung, Betarezeptoren-blocker wahrend der Narkose nur bei strengster Indikation zu verabreichen und sie nur unter sorgfaltig kontrollierten Bedingungen anzuwenden.