Resilient liner vs. clip attachment effect on peri‐implant tissues of bar‐implant‐retained mandibular overdenture: a 1‐year clinical and radiographical study

Purpose: The aim of this study was to compare between the effects of resilient liner and clip attachments of bar‐implant‐retained mandibular overdenture on peri‐implant tissues. Materials and methods: In a randomized‐controlled clinical trial, 30 edentulous male patients (mean age 62.5 years) were equally assigned to two groups. In each patient, two implants were inserted in the canine area of the mandible using a two‐stage surgical protocol. After 3 months, the implants were connected with resilient bars. Mandibular overdentures were retained to the bars with either clips (group I) or silicone‐resilient liners (group II). Peri‐implant tissues were evaluated clinically (with regard to plaque scores, gingival scores and probing depths) and radiographically (with regard to peri‐implant vertical and horizontal alveolar bone changes). Evaluations were performed at the time of overdenture insertion (T0), 6 months (T6) and 12 months (T12) after overdenture insertion. Results: After 12 months of using bar‐implant‐retained mandibular overdenture, the resilient liner attachment had significantly decreased peri‐implant plaque score, gingival score, probing depth, vertical and horizontal bone loss when compared with the clip attachment. Conclusion: Within the limitations of this study, and in terms of peri‐implant tissue health of bar‐implant‐retained mandibular overdenture, we recommend resilient liner rather than clip attachment. To cite this article:
Elsyad MA, EL Shoukouki AH. Resilient liner vs. clip attachment effect on peri‐implant tissues of bar‐implant‐retained mandibular overdenture: a 1‐year clinical and radiographical study.
Clin. Oral Impl. Res. 21 , 2010; 473–480
doi: 10.1111/j.1600‐0501.2009.01879.x     

Antibodies to the three major glycoproteins of varicella-zoster virus: search for the relevant host immune response

Clinical manifestations of chickenpox have occurred in individuals known to have seroconverted after vaccination against varicella. To determine whether these "breakthroughs" might be due to the absence of specific antibodies, we tested sera from vaccinees before or at the time of exposure to varicella for antibodies to the three major glycoproteins of varicella-zoster virus (VZV). Protection could not be correlated with the presence or level of any of these antibodies. Levels of antibodies to glycoproteins before onset of zoster were similar to those in sera of individuals who had had varicella previously and did not develop varicella after household exposure. Thus, protection against infections with VZV cannot be explained by the presence of specific antibodies to glycoproteins.     

Further delineation of the KBG syndrome caused by ANKRD11 aberrations

Loss-of-function variants in ANKRD11 were identified as the cause of KBG syndrome, an autosomal dominant syndrome with specific dental, neurobehavioural, craniofacial and skeletal anomalies. We present the largest cohort of KBG syndrome cases confirmed by ANKRD11 variants reported so far, consisting of 20 patients from 13 families. Sixteen patients were molecularly diagnosed by Sanger sequencing of ANKRD11, one familial case and three sporadic patients were diagnosed through whole-exome sequencing and one patient was identified through genomewide array analysis. All patients were evaluated by a clinical geneticist. Detailed orofacial phenotyping, including orthodontic evaluation, intra-oral photographs and orthopantomograms, was performed in 10 patients and revealed besides the hallmark feature of macrodontia of central upper incisors, several additional dental anomalies as oligodontia, talon cusps and macrodontia of other teeth. Three-dimensional (3D) stereophotogrammetry was performed in 14 patients and 3D analysis of patients compared with controls showed consistent facial dysmorphisms comprising a bulbous nasal tip, upturned nose with a broad base and a round or triangular face. Many patients exhibited neurobehavioural problems, such as autism spectrum disorder or hyperactivity. One-third of patients presented with (conductive) hearing loss. Congenital heart defects, velopharyngeal insufficiency and hip anomalies were less frequent. On the basis of our observations, we recommend cardiac assessment in children and regular hearing tests in all individuals with a molecular diagnosis of KBG syndrome. As ANKRD11 is a relatively common gene in which sequence variants have been identified in individuals with neurodevelopmental disorders, it seems an important contributor to the aetiology of both sporadic and familial cases.     

MARS (Molecular Adsorbent Recirculating System): experience in 34 cases of acute liver failure

As reported in the literature, the mortality rates for patients with Acute Hepatic Failure (AHF) approaches 80% in cases in which liver transplantation is not possible. Post-transplant mortality mostly depends on the severity of the neurological condition at the time of the operation (20% in I-II degree coma patients and 44% in III degree coma patients). The primary indications for liver transplantation in AHF are Fulminant Hepatitis (FH)(93%), Subfulminant Hepatitis (5%) and other indications (2%). Other causes of AHF are Primary Non-Function (PNF) and Delayed Function (DF), which occur in 7-10%. Therefore it becomes necessary to monitor the patients with a Liver Support Device to be able to improve the clinical condition of the patients before liver transplantation (LT). In our experience we used the Molecular Adsorbent Recirculating System (MARS) (MARS Monitor; Teraklin AG, Rostock Germany), which enables the selective removal of albumin-bound substances accumulating in liver failure by the use of albumin-enriched dialysate. The system is used as a bridging device to orthotopic liver transplantation (OLT) of patients with FHF. We studied 34 patients, including 16 males and 18 females: 9 were affected by Primary-Non-Function (PNF), nine by Fulminant Hepatitis (FH), six by Delayed-Non-Function (DNF), and ten by Acute on Chronic Hepatic Failure (AOCHF). The average age of the patients was 41.8 years and the average number of applications was 6.4; the median length of application was about eight hours. The parameters that we monitored, before and after each treatment, were neurological status (EEG, cerebral CT, Glasgow Coma Score), haemodynamic parameters, acid base equilibrium, and blood gas analysis. We also monitored hepatic and renal function. In addition, the clinical conditions of the patients were monitored using kidney and liver ultrasound/ultrasonography (US). Inclusion criteria were bilirubin > 15 mg/dL, ammonia > 160 micro g/dL and a Glasgow Coma Score between 6 and 11. The reduction of bilirubin and ammonia were very significant (P < 0.01), whereas the changes of International Normalized Ratio (INR) were not significant. Also the modifications of albumin, total protein, sodium, potassium and calcium were not significant. In conclusion, four out of nine patients with PNF are alive without a second transplantation and were discharged after about 48 days; four out of nine underwent OLT, while one out of nine died; five out of six patients with DF are alive without a second transplantation, and they were discharged after an average time of 55.5 days, one out of six died; six out of nine patients with fulminant hepatitis underwent OLT and four of these are alive, while two died due to sepsis; three patients are alive without OLT. Four patients with AOCHF underwent OLT and are alive, three patients are alive and on a waiting list, two died while on a waiting list and one patient who experienced reactivation of HBV infection during chemotherapy for non-Hodgkin's lymphoma is alive. In spite of the limited number of cases of our study, we believe that MARS can be applied with high tolerance for a very long period of time. In addition, its repeatability allows it to be used in patients with DNF and FH as a bridge to transplant. In patients with DNF, it is used while waiting for complete recovery of the transplanted organ.     

Could neonatal disseminated herpes simplex virus infections be treated earlier?

INTRODUCTION: Neonatal disseminated herpes simplex virus (HSV) infection can cause rapidly progressive multiple organ failure with an 85% mortality if untreated. Early recognition and treatment may improve outcome [N Engl J Med 324(1991)450]. OBJECTIVES: (i) To determine the number and presentation of neonates with disseminated HSV admitted to an intensive care unit. (ii) To determine paediatric Specialist Registrar (SpR) awareness of the diagnosis and management of a typical potential case of neonatal disseminated HSV. METHODS: (i) A 10-year review of case notes of neonates admitted to the intensive care unit (ICU) at Great Ormond Street Hospital. (ii) A telephone questionnaire of 'on-call' Paediatric SpR's in the London area. RESULTS: Eight cases of confirmed disseminated HSV infection were identified. All died. Each case followed a similar clinical course with presentation between days 5-9 of life (median day 7). A short prodrome preceded the rapid development of disseminated intravascular coagulopathy (DIC), hepatitis and multiple organ failure. Only three cases received antiviral treatment in the first 24 h after hospital admission. None of the 30 registrars who were interviewed initially considered disseminated HSV in the differential diagnosis of a 7-day-old baby presenting with non-specific signs of sepsis. Only 4/30 referring unit protocols included disseminated HSV in the differential diagnosis of neonatal sepsis. CONCLUSIONS: HSV infection should be considered in the differential diagnosis of the acutely unwell neonate. This condition is rare but well documented in the literature. Effective antiviral therapies exist but are often not started early in the clinical course. Awareness of this condition needs to be increased.     

Thiocarbohydrazide-crosslinked chitosan as a bioinspired corrosion inhibitor for protection of stainless steel in 3.5% NaCl

A facile single-step synthesis was performed to cross-link chitosan with thiocarbohydrazide to yield thiocarbohydrazide-chitosan (TC-Cht) which was for the first time evaluated as an inhibitor for corrosion of stainless steel in 3.5% NaCl solution. A comprehensive electrochemical analysis employing electrochemical impedance spectroscopy (EIS), potentiodynamic polarization (PDP), and cyclic voltammetry (CV) was undertaken and showed that the TC-Cht acts by adsorption on the steel surface and exhibits mixed type behavior with predominantly cathodic nature. The adsorption of TC-Cht molecules on the surface of stainless steel followed the Langmuir isotherm. The TC-Cht showed a high inhibition efficiency of >94% at 500 mg L^?1 concentration. Surface investigation using SEM and EDX supported the inhibitor adsorption on the steel surface.     

Heterozygous germline BLM mutations increase susceptibility to asbestos and mesothelioma

Rare biallelic BLM gene mutations cause Bloom syndrome. Whether BLM heterozygous germline mutations (BLM^+/−) cause human cancer remains unclear. We sequenced the germline DNA of 155 mesothelioma patients (33 familial and 122 sporadic). We found 2 deleterious germline BLM^+/− mutations within 2 of 33 families with multiple cases of mesothelioma, one from Turkey (c.569_570del; p.R191Kfs*4) and one from the United States (c.968A>G; p.K323R). Some of the relatives who inherited these mutations developed mesothelioma, while none with nonmutated BLM were affected. Furthermore, among 122 patients with sporadic mesothelioma treated at the US National Cancer Institute, 5 carried pathogenic germline BLM^+/− mutations. Therefore, 7 of 155 apparently unrelated mesothelioma patients carried BLM^+/− mutations, significantly higher (P = 6.7E-10) than the expected frequency in a general, unrelated population from the gnomAD database, and 2 of 7 carried the same missense pathogenic mutation c.968A>G (P = 0.0017 given a 0.00039 allele frequency). Experiments in primary mesothelial cells from Blm^+/− mice and in primary human mesothelial cells in which we silenced BLM revealed that reduced BLM levels promote genomic instability while protecting from cell death and promoted TNF-α release. Blm^+/− mice injected intraperitoneally with asbestos had higher levels of proinflammatory M1 macrophages and of TNF-α, IL-1β, IL-3, IL-10, and IL-12 in the peritoneal lavage, findings linked to asbestos carcinogenesis. Blm^+/− mice exposed to asbestos had a significantly shorter survival and higher incidence of mesothelioma compared to controls. We propose that germline BLM^+/− mutations increase the susceptibility to asbestos carcinogenesis, enhancing the risk of developing mesothelioma.

In the United States, the incidence rate of mesothelioma varies between fewer than one case per 100,000 persons in states with no asbestos industry to two to three cases per 100,000 persons in states with an asbestos industry (1, 2). Asbestos causes DNA damage and apoptosis (3) and promotes a chronic inflammatory reaction that supports the emergence of malignant cells (4). Fortunately, only a small fraction of exposed individuals develop mesothelioma; for example, 4.6% of deaths in miners who worked in asbestos mines for over 10 y were caused by mesothelioma (1). Therefore, multiple cases of mesothelioma in the same family are rare and suggest genetic predisposition (5). In 2001, we discovered that susceptibility to mesothelioma was transmitted in a Mendelian fashion across multiple generations in some Turkish families exposed to the carcinogenic fiber erionite, pointing to gene × environment interaction (G×E) as the cause (6). In 2011, we discovered that carriers of heterozygous germline BRCA1-associated protein–1 (BAP1) mutations (BAP1^+/−) developed mesothelioma and uveal melanoma (5), findings expanded and confirmed by us and by multiple research teams (reviewed in refs. 1, 7, 8). Moreover, heterozygous germline Bap1 mutations (Bap1^+/−) significantly increased susceptibility to asbestos-induced mesothelioma in mice (9, 10), evidence of G×E. Reduced BAP1 levels impair DNA repair (11) as well as different forms of cell death (3, 12) and induce metabolic alterations (13–15) that together favor cancer development and growth.Recent studies revealed that mesothelioma may also develop among carriers of germline mutations of additional tumor-suppressor genes that cause well-defined cancer syndromes, including MLH1 and MLH3 (Lynch syndrome), TP53 (Li–Fraumeni syndrome), and BRCA1-2 (Breast and Ovarian Cancer syndrome) (16, 17). When all germline mutations are combined, it has been estimated that about 12% of mesotheliomas occur in carriers of heterozygous germline mutations of BAP1, the most frequent mutation among patients with mesothelioma, or of other tumor suppressors. Some of these mutations may sensitize the host to asbestos carcinogenesis, according to a G×E scenario (17). Thus, presently, mesothelioma is considered an ideal model to study G×E in cancer (17). As part of the Healthy Nevada Project (HNP), we are studying G×E in northern Nevada, a region with an unusually high risk of exposure to carcinogenic minerals and arsenic, which may be related to the high cancer rates in this region (18). We are investigating genetic variants that may increase cancer risk upon exposure to carcinogens to implement preventive strategies.Biallelic mutations of the Bloom syndrome gene (BLM) cause Bloom syndrome, an autosomal-recessive tumor predisposition syndrome characterized by pre- and postnatal growth deficiency, photosensitivity, type 2 diabetes, and greatly increased risk of developing various types of cancers. BLM is a RecQ helicase enzyme that modulates DNA replication and repair of DNA damage by homologous recombination (19). In patients affected by Bloom syndrome, the absence of the BLM protein causes chromosomal instability, increased number of sister chromatid exchanges, and increased numbers of micronuclei (20–22). In addition, BLM is required for p53-mediated apoptosis (23), a process critical to eliminate cells that have accumulated DNA damage. Impaired DNA repair together with altered apoptosis resulted in increased cancer incidence (17, 24). Of course, inactivating germline BLM heterozygous (BLM^+/−) mutations are much more common than biallelic BLM (BLM^−/−) mutations, with an estimated frequency in the general population of 1 in 900 based on data from the Exome Aggregation Consortium (25). BLM^+/− mutation carriers do not show an obvious phenotype; however, some studies have suggested that carriers of these mutations may have an increased cancer risk (17, 24). Mice carrying Blm^+/− mutations are prone to develop a higher rate of malignancies in the presence of contributing factors, such as concurrent heterozygous mutations of the adenomatous polyposis coli (Apc) gene, or upon infection with murine leukemia virus (26). However, in studies in which Blm^+/− mice were crossed with tuberous sclerosis 1-deficient (Tsc1^+/−) mice that are predisposed to renal cystadenomas and carcinomas, Wilson et al. found that Tsc1^+/− Blm^+/− mice did not show significantly more renal cell carcinomas compared with Tsc1^+/− Blm^WT mice (27). In humans, a large study involving 1,244 patients with colon cancer and 1,839 controls of Ashkenazi Jewish ancestry, in which BLM^+/− frequency is as high as 1 in 100 individuals (28), suggested that carriers of germline BLM^+/− mutations might have a twofold increase in colorectal cancer (CRC) (29). A smaller study did not confirm these results, but reported a trend of increasing incidence of adenomas—premalignant lesions—among BLM^+/− mutation carriers (30). In addition, BLM^+/− mutations were found overrepresented among early-onset (<45 y old) CRC patients (25). Other studies associated BLM^+/− mutations to an increased risk of breast (31, 32) and prostate cancer (33), but the low power of these studies hampered definite conclusions. In summary, it appears possible that BLM^+/− mutations may increase cancer risk in the presence of contributing factors.