Treatment of temporomandibular disorders with a combination of hard acrylic stabilisation appliance and a soft appliance in the opposing jaw. A retro- and prospective study

The aim of this study was to evaluate the treatment effect of a combined treatment with a stabilisation appliance and a soft appliance in the opposing jaw in patients refractory to previous TMD treatment. During a 5-year-period, 2001-2005, a total of 98 patients received the combined treatment at the Department of Stomatognathic Physiology, the Institute for Postgraduate Dental Education, J?nk?ping, Sweden. Before the patients received the combined treatment, they had already been given several different TMD treatments during a long period of time, either before referral or at the specialist clinic, with only minor or no effect on their TMD symptoms. The patients were followed prospectively (n=10), or analysed retrospectively (n=88). The data registered were gender, age, main indication for TMD treatment, number of visits to the clinic before and after the introduction of the combined treatment, as well as according to a clinical (Di) and anamnestic (Ai) dysfunction index. The most common causes for treatment in the retrospective material were problems of muscular origin and problems of both muscular and TMJ origin. In the prospective material, most of the patients had mainly muscular symptoms. Both the clinical and anamnestic dysfunction index decreased statistically significantly in the retrospective material after the introduction of the combined treatment. There was a numerical improvement of both indices also in the prospective material. In conclusion, the present investigation showed that a combined treatment with a hard acrylic stabilisation appliance and a soft appliance in the opposing jaw seems to give a remarkable improvement of TMD signs and symptoms in apparently therapy resistant TMD patients. General conclusions should, however, be made with caution due to the fact that the study did not include any control group. There is an obvious need for randomized controlled studies concerning the efficacy and effectiveness of the combined treatment presented in this study.     

Quantitative real-time RT-PCR assay for PCA3

Objectives:To develop a quantitative, internally standardized real-time RT-PCR assay for prostate cancer antigen 3 (PCA3), a non-translated gene found to be prostate-specific and highly overexpressed in cancer, and examine the role of PCA3 in peripheral blood with a small sample cohort.Design and methods:The RT-PCR assay for PCA3 is based on target-specific lanthanide probes. Peripheral blood from 91 prostatic cancer/disorder patients and healthy controls was assayed for PCA3 and prostate-specific antigen (PSA) expression.Results:The dynamic range of the assay reaches over eight orders of magnitude and the limit of quantification is 800 copies per milliliter blood. Peripheral blood from 2/9 patients with metastasized cancers were PCA3 positive, whereas all the other samples were negative. Eight samples were PSA positive.Conclusions:The degree of PCA3 positivity in circulating cells from prostate cancer patients is low compared to that of PSA. In contrast to some previous reports, we found no PCA3 expression in healthy individuals.     

Modelling the risk of noise-induced hearing loss among military pilots

Noise is a significant risk factor in aviation, especially in military aviation. Even though our earlier studies have shown that the risk of noise-induced hearing loss (NIHL) among military pilots is small and the monitoring of their hearing is effective, we still need to develop methods of assessing the risk of NIHL more effectively at both the general and individual levels. In addition, many other risk factors are considered to contribute to the development of hearing impairment. The novel NoiseScan data management system enables assessment of the risk of developing hearing impairment on the basis of known risk factors. This study investigates the risk of hearing impairment among Finnish Air Force pilots using reasonably accurate noise exposure data and other risk factors for hearing impairment. This risk is also compared with that of industrial workers, whose risk followed the ISO 1999 prediction. Hearing among Finnish military pilots turned out to be better than predicted by the ISO 1999 model. The industrial workers had a larger number of risk factors than the pilots. Owing to the small number of risk factors, the hearing of pilots corresponds to approximately the 80th percentile, being 9-13 dB better than the 50th percentile obtained with the industrial population.     

Family and twin studies in inflammatory bowel disease

Studies examining the inheritance of inflammatory bowel disease (IBD) within different family groups have been the basis for recent molecular advances in the genetics of IBD. The derived heritability in Crohn's disease (CD) is higher than in many other complex diseases. The risk of IBD is highest in first-degree relatives of a CD proband, but first-degree relatives of a proband suffering from ulcerative colitis (DC) and more distant relatives are also at increased risk. Disease concordance rates in IBD have been examined in multiplex families and in three large European twin studies.     

Effect of intervention on decision making of treatment for disease progression,prostate‐specific antigen biochemical failure and prostate cancer death

Background

Patient preference for the choice of treatment modality for prostate cancer has increasingly gained attention.

Objective

To assess the impact of client‐oriented decision on long‐term mortality, disease progression and biochemical failure compared with standard treatment protocol (TP).

Methods

With data from a Finnish multicentre, randomized controlled trial with two arms [104 in the enhanced patient participation (EPP) arm and 106 in the TP arm], disease‐specific and disease‐free survival, biochemical failure with elevated prostate‐specific antigen (PSA) level and disease progression were compared between the two arms using Wilcoxon test and also Cox proportional hazards regression model.

Results

Patients in the EPP arm had a higher risk of death by 37% [HR, 1.37 (0.87–2.17)] compared with those in the TP arm. Patients in the EPP arm were at increased risk of having biochemical failure by 14% [HR, 1.14 (0.72–1.79)] and for having disease progression by 2% [HR, 1.02 (0.61–1.70)] compared with those in the TP arm. All the differences were non‐significant.

Conclusions

Patients actively involved in the choice of treatment had higher risk of prostate cancer death but only slightly increased risk of biochemical failure and clinical disease progression. These findings would provide a good reference when patient autonomy for the choice of treatment modality is addressed.     

New polymyxin derivatives that display improved efficacy in animal infection models as compared to polymyxin B and colistin

Polymyxin B and colistin (polymyxin E) are bactericidal pentacationic lipopeptides that act specifically on Gram‐negative bacteria, first by disrupting their outermost permeability barrier, the outer membrane (OM), and then damaging the cytoplasmic membrane. The discovery of both polymyxin B and colistin was published independently by three laboratories as early as in 1947. They were subsequently used in intravenous therapy. Unfortunately, they also exhibit significant and dose‐limiting nephrotoxicity. Therefore, polymyxins were reserved as agents of last‐line defense. The emergence of extremely multiresistant strains has now forced clinicians to reinstate polymyxins in the therapy of severe infections. However, the current dosage regimens lead to insufficient drug concentrations in serum and clinicians have been advised to use larger doses, which further increases the risk of nephrotoxicity. Very recently, the interest in developing better tolerated and more effective polymyxins has grown. This review focuses on describing four development programs that have yielded novel derivatives that are more effective than the old polymyxins in animal infection models. Compounds from three programs are superior to the old polymyxins in the rodent lung infection model with Acinetobacter baumannii and/or Pseudomonas aeruginosa. One of them is also more effective than polymyxin B in A. baumannii mouse thigh infection. The fourth program includes compounds that are approximately tenfold more effective in Escherichia coli murine pyelonephritis than polymyxin B.     

Augmented cellular trafficking and endosomal escape of porous silicon nanoparticles via zwitterionic bilayer polymer surface engineering

The development of a stable vehicle with low toxicity, high cellular internalization, efficient endosomal escape, and optimal drug release profile is a key bottleneck in nanomedicine. To overcome all these problems, we have developed a successful layer-by-layer method to covalently conjugate polyethyleneimine (PEI) and poly(methyl vinyl ether-co-maleic acid) (PMVE-MA) copolymer on the surface of undecylenic acid functionalized thermally hydrocarbonized porous silicon nanoparticles (UnTHCPSi NPs), forming a bilayer zwitterionic nanocomposite containing free positive charge groups of hyper-branched PEI disguised by the PMVE-MA polymer. The surface smoothness, charge and hydrophilicity of the developed NPs considerably improved the colloidal and plasma stabilities via enhanced suspensibility and charge repulsion. Furthermore, despite the surface negative charge of the bilayer polymer-conjugated NPs, the cellular trafficking and endosomal escape were significantly increased in both MDA-MB-231 and MCF-7 breast cancer cells. Remarkably, we also showed that the conjugation of surface free amine groups of the highly toxic UnTHCPSi-PEI (Un-P) NPs to the carboxylic groups of PMVE-MA renders acceptable safety features to the system and preserves the endosomal escape properties via proton sponge mechanism of the free available amine groups located inside the hyper-branched PEI layer. Moreover, the double layer protection not only controlled the aggregation of the NPs and reduced the toxicity, but also sustained the drug release of an anticancer drug, methotrexate, with further improved cytotoxicity profile of the drug-loaded particles. These results provide a proof-of-concept evidence that such zwitterionic polymer-based PSi nanocomposites can be extensively used as a promising candidate for cytosolic drug delivery.     

Epidemiology,risk of malignancy and patient survival in primary sclerosing cholangitis: a population-based study in Finland

Abstract

Background: There are only a few and mostly small population-based epidemiological studies of primary sclerosing cholangitis (PSC).

Objective: We aimed to estimate prevalence and incidence rates of PSC, and survival and malignancy risk for PSC patients in a large population-based study.

Methods: We retrieved 632 PSC patients from 1990 to 2015 in the Hospital District of Helsinki and Uusimaa (HUS), comprising 29% of the Finnish population. Mortality information of the PSC patients was obtained from the national Population Registry, malignancy information from the Finnish Cancer Registry and the causes of death from the Statistics Finland. Standardized incidence ratio and standardized mortality ratio (SMR) were calculated for predefined malignancy types.

Results: The crude incidence of PSC in the HUS area was 1.58/100,000 person-years, and the point prevalence in 2015 was 31.7/100,000 inhabitants. The mean time from diagnosis to death was 21.9 years. The risk for any malignancy was three-fold and the risk for colorectal carcinoma was five-fold when comparing with the general population. During the first year after diagnosis of PSC, the risk for cholangiocarcinoma is 900-fold compared to the general population and after that 150-fold. SMR for all malignant neoplasms was 5.9 (95% CI 4.2–8.1).

Conclusion: We found that the incidence of PSC in the HUS area in Finland is similar or higher than previously reported from other countries. The prevalence is markedly higher than reported elsewhere, probably due to the active search of the disease, suggesting that the disease is underdiagnosed.     

Lifestyle and metabolic factors in relation to shoulder pain and rotator cuff tendinitis: A population-based study

Background  

Shoulder pain is a common health problem. The purpose of this study was to assess the associations of lifestyle factors, metabolic factors and carotid intima-media thickness with shoulder pain and chronic (> 3 months) rotator cuff tendinitis.     

Clinical value of ultrasound in the evaluation of dyspepsia in primary health care

OBJECTIVE: In general practice, upper abdominal ultrasound (US) is widely used in the evaluation of patients with dyspepsia. However, there is a dearth of published data on the role of US in the dyspepsia work-up. There are no data on the use of US as a follow-up study in functional dyspepsia. The aims of this study were to assess the role of US in evaluating dyspepsia, and to assess the long-term clinical relevance of minor findings revealed by US in patients with functional dyspepsia. MATERIAL AND METHODS: Four hundred consecutive dyspeptic patients were recruited. At baseline, all patients underwent gastroscopy and US. Patients were divided into two groups: "endoscopy-negative patients" and "endoscopy-positive patients". "The endoscopy-negative" group included all cases in which the final diagnoses could not be settled after gastroscopy. US was repeated after 6-7 years in patients who had functional dyspepsia. RESULTS: In the endoscopy-negative group, gallstones were detected in 21 patients, but this was considered to be a cause of symptoms in 9 patients. No malignant lesions were detected by US in the endoscopy-negative group. In the endoscopy-positive group, a malignant tumor in the kidney was suspected in 3 patients. Only one of these tumors turned out to be an incidental small carcinoma. Moreover, several minor findings were shown by US: usually these consisted of abnormal echogenicity of the liver. During the follow-up period, 6 patients developed gallstones. At the end of the follow-up period, two clinically significant findings were diagnosed: a small renal cancer and hydronephrosis. CONCLUSIONS: This study shows that the wide, untargeted use of abdominal US in the evaluation of patients with dyspepsia following a gastroscopy is not necessary. Repeated US examination in cases of functional dyspepsia is not recommended, and rarely changes the diagnosis.