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In an observational prospective study, feasibility and outcomes of a dedicated multidisciplinary rehabilitation program (HNR) for head and neck cancer (HNC) patients were evaluated. HRQoL was assessed before and after HNR with EORTC C30 and H&N-35 QoL questionnaires in 52 consecutive patients. Initial HRQoL scores were compared with EORTC reference scores for HNC patients and post-HNR with those available for the general healthy population. Distress was assessed before and after HNR with the distress thermometer (DT). At completion of HNR with a mean duration of 7 months, overall HRQoL was significantly improved (p < 0.001). Role, Emotional, and Social function scales and most EORTC C30 and H&N35 symptom scale items showed a statistically significant (p < 0.01) and clinically relevant improvement. Mean distress score before HNR was above the cutoff value of 5, suggesting the need for referral to rehabilitation. After completing HNR, distress decreased significantly to 3.0 (p < 0.001). HRQoL pretreatment was poorer than that of the EORTC reference HNC population, whereas at the completion of the HNR program, the HRQoL was comparable to that of the general population reference level. We conclude that a dedicated multidisciplinary HNR program is feasible and suggest that it has a positive impact on HRQoL. The multidisciplinary approach may have added value over mono-disciplinary interventions. However, our results should be judged cautiously due to the observational nature of the study.

Objectives: Data from a vaccine trial and from post-vaccine surveillance in the United Kingdom have suggested that the bivalent HPV-16/18 vaccine offers cross-protection against HPV-6/11 and protection against anogenital warts (AGW). We studied the effect of the bivalent vaccine on genital HPV-6/11 positivity and AGW in the Netherlands.Methods: We included all vaccine-eligible women from the PASSYON study, a biennial cross-sectional study among 16- to 24-year-old sexually transmitted infection (STI) clinic attendants. Vaginal self-swabs were analyzed for type specific HPV and AGW were diagnosed at the STI-clinic. Prevalence of HPV-6 and/or HPV-11 and AGW were compared between self-reported vaccinated and unvaccinated women by log-binomial regression analysis, adjusted for demographics and risk behavior.Results: Of the 1198 women included, 56% reported to be vaccinated at least once. Relative to unvaccinated women, the adjusted prevalence ratio (PR) for HPV-6/11 was 1.03 (95% confidence interval [CI] 0.74-1.43) for women vaccinated at least once. The crude PR for AGW was 0.67 (95% CI 0.22-2.07) for women vaccinated at least once. Adjustment did not change these results.Conclusions: We observed no cross-protective effect of the bivalent vaccine on genital HPV-6/11 positivity and a non-significant partially protective effect on AGW. (C) 2017 The Authors. Published by Elsevier Ltd on behalf of The British Infection Association.

To manage environmental problems in an adequate way, it is essential to take different spatial scales into consideration. As a tool for decision making, it would be beneficial if valuation methods take spatial scales into account as well. In this article, we review the valuation literature with regard to the spatial scales of environmental public goods and services to which the contingent valuation method, hedonic pricing method, and travel cost method have been applied in the past. We classified 117 environmental case studies to the local, landscape/watershed, regional, and global scales. These case studies cover a broad range of environmental goods and services, such as green space in a city, air quality, rivers, natural areas, and a stable climate system. Additionally, we took into account the year of publication of the case studies. Our results show that the majority of the environmental case studies are related to the local and landscape/watershed scales. However, the number of case studies on the regional and global scales has been increasing in recent years. This article argues that such a change in spatial scale calls for a debate on scaling issues in the field of environmental valuation.

In this paper we evaluate the relationships between household expenditures and the environmental impact categories climate change, acidification, eutrophication and smog formation, by combining household expenditures with environmentally extended input–output analysis. Expenditure elasticities are examined with regression analysis, and are compared and interpreted on the basis of insight at the product level. With data from the Netherlands in the year 2000, we find that environmental impact increases with increasing household expenditures, although the degree to which the environmental impact increases differs per impact category. Climate change and eutrophication increase less than proportionally with increasing expenditures. Acidification increases nearly proportionally with increasing expenditures, whereas smog formation increases more than proportionally. It appears that the mix of necessities and luxuries to which an environmental impact is related is essential in explaining the relationship.

Current economic instruments aimed at climate change mitigation focus on CO2 emissions only, but the Kyoto Protocol refers to other greenhouse gases (GHG) as well as CO2. These are CH4, N2O, HFCs, PFCs and SF6. Taxation of multiple greenhouse gases improves the cost-effectiveness of climate change mitigation. It is not yet clear, however, what the effect is of multigas taxation on the distribution of the tax burden across income groups. This paper examines and compares distributional effects of a CO2 tax and a comprehensive tax that covers all six GHG of the Kyoto Protocol. The study concentrates on the Netherlands in the year 2000. We established tax rates on the basis of marginal abatement cost curves and the Dutch policy target. The distributional effects have been determined by means of environmentally extended input−output analysis and data on consumer expenditures. Our results show that taxation of multiple GHG improves not only the cost-effectiveness of climate change mitigation, but also distributes the tax burden more equally across income groups as compared to a CO2 tax. These findings are relevant for the debate on the role of non-CO2 GHG in climate change mitigation.

The present study is a retrospective search on the actual use of systemic retinoids in the treatment of psoriasis. The design of the study was inclusion of the patients in whom retinoid treatment was initiated from 1981 up to 1989. The analysis was carried out in 1999, after at least 10 years of follow up. In total 94 patients were included, who were treated with etretinate or acitretin, out of a cohort of 2,000 patients with psoriasis at the Nijmegen Department of Dermatology. The majority of the patients were older than 40 years, 31% were suffering from pustular psoriasis, 6% from erythrodermic psoriasis and 17% from psoriasis arthropatica. Most patients had had psoriasis for more than 5 years and in 56% of them retinoids were the first systemic treatment. Continuous treatment for more than one year was recorded in 33% of the patients. During long-term follow up of at least 10 years, 25% of them were included again for acitretin treatment. Therefore, prolonged treatment actually had occurred in approximately half of the patients. In contrast to the common belief, erythrodermic psoriasis proved to be not the typically "low-dose" - and pustular psoriasis was not the typically "high dose" indication. The present study, however, reconfirmed the high efficacy of systemic retinoids in pustular- and erythrodermic psoriasis. It was also reconfirmed that systemic retinoids are not effective in arthropathic psoriasis. The occurrence of side effects largely followed the controlled investigations. At least 10 years' follow up had not revealed serious side effects. In those patients (n = 30) who completed the entire survey in the Nijmegen centre 19 patients were treated with at least one course of photo(chemo)therapy and 9 patients were treated subsequently with methotrexate.

Two women, aged 27 and 42 years, both born in Surinam and both suffering from heterozygous thalassemia, developed cholestatic hepatitis three and two weeks respectively after the start of a two-day course of thiabendazol for Strongyloides stercoralis infection. Other causes of cholestasis were unlikely in view of the results of blood tests, echography and the endoscopic retrograde cholangiopancreaticography. The symptoms persisted for several months, and the liver function disorders for 7 years and one year, respectively. The incidence of thiabendazole-induced cholestatic hepatitis is unknown, but probably low.

In three alcoholic patients, two men aged 30 and 42, and a woman aged 52, hepatitis was diagnosed after the use of disulfiram. In all cases, there was a close temporal relationship between the occurrence of symptoms and disulfiram intake. Other possible causes were excluded. The 30-year-old man died from liver damage. Biopsy showed massive hepatic necrosis without signs of alcoholic hepatitis. In the other patients, symptoms subsided quickly and liver function returned to normal after discontinuation of disulfiram, but there was no confirmation by biopsy. The possibility of drug-induced hepatitis should always be considered in an alcoholic patient treated with disulfiram.

A 70-year-old woman suffering from atrial fibrillation was treated with amiodarone, but developed acute respiratory failure necessitating mechanical ventilation for four weeks. Pulmonary function remained restrictively impaired after weaning from the ventilation, due to pulmonary fibrosis. Pulmonary toxicity is a well-known adverse reaction to amiodarone, but it rarely requires mechanical ventilation. The Netherlands Centre for Monitoring of Adverse Reactions to Drugs received II reports of this life-threatening reaction since 1976.

A sensitive radiochemical method for the determination of the pyruvate dehydrogenase complex (PDHC) activity in skeletal muscle tissue, based on the decarboxylation of [1-14C]-pyruvate to 14CO2, is described. Measurements can be carried out either in muscle homogenate or in 600-g supernatant, both obtainable from a small muscle biopsy specimen (20 mg). In addition to NAD+, thiamine pyrophosphate and coenzyme A in the incubation mixture, a preparation of NADH:cytochrome c reductase (NADHCR) together with cytochrome c has a stimulating effect on the PDHC activity. NADHCR constitutes an oxidation system for NADH to prevent feedback inhibition. Addition of L-carnitine also results in stimulation of PDHC by trapping the produced acetyl-CoA as acetylcarnitine. Special care for radioactive pyruvate, with freeze drying and storage at -20 degrees C under nitrogen, and determination of the purity during every PDHC assay, is required. In the presented assay a Km value of 0.084 mmol/l was found for pyruvate. Nonsigmoidal kinetics was found with a Hill coefficient of 1.63. With the described method, a totally Mg2+,Ca(2+)-stimulated PDHC activity is measured. Addition of a purified specific pyruvate dehydrogenase phosphatase did not yield a higher PDHC activity. Finally, comparison of total PDHC activity with [1-14C]-pyruvate oxidation rates, both measured in the supernatant prepared from fresh muscle, shows an equimolar correlation, indicating that total PDHC activity is rate limiting in the assay for the pyruvate oxidation rate. Neonatal muscle exhibits five to ten times lower PDHC activities and pyruvate oxidation rates than controls (age > 3 years).

An infant with moderate muscular hypotonia and congenital lactic acidosis died suddenly at the age of 3 months. Autopsy revealed no abnormalities responsible for this unexpected death. Measurement of mitochondrial enzymes involved in energy production indicated a severely decreased total pyruvate dehydrogenase complex (PDHC) activity in muscle tissue (0.23 nmoles x min-1 x mg protein-1, control range 2.8-8.7) and moderately decreased PDHC activity in fibroblasts (0.27 nmoles x min-1 x mg protein-1, control range 0.37-2.32). The activity of the first component E1 (pyruvate dehydrogenase) in muscle tissue was 10 times lower than that of controls (0.008 nmoles x min-1 x mg protein-1, control range 0.10-0.25). The activities of dihydrolipoyl dehydrogenase (E3) and various other mitochondrial enzymes were normal. Immunochemical analysis in skeletal muscle tissue and fibroblasts demonstrated a decrease in the amount of the alpha and beta subunits of E1. The features of this patient are compared with those of other patients reported in the literature with immunochemically confirmed combined E1 alpha and beta deficiency.

One of the main functions of the circulation is the transportation of oxygen. A priori, reasoning would indicate that there is a close correlation between oxygen consumption and rate of oxygen transportation. Grollman1 expressed this supposed relationship in his “cardiac index” which correlates minute volume at rest with square meters of body surface. He defines “cardiac index” as the minute volume per square meter of body surface. In a large series of determinations on normal individuals, he found that his “cardiac index” was 2.2 liters per square meter of body surface. The standard deviation in this series of determinations was 0.3. Grollman's cardiac index does not take into account the variability in the basal metabolic rate of normals. As we know, this rate varies —15 to +15 in any large series of normal cases. Believing that a better cardiac index could be obtained by taking into consideration the basal metabolic rate, we have constructed a formula which fits the determination somewhat better than t...

Lewis,1 using dogs and cats, was able to demonstrate that the minute output of the heart was decreased about 20% when the auricles were caused to fibrillate by faradic stimulation. He made the observation also that the more rapid the ventricular rate, the greater the decrease in minute volume.Eyster and Swarthout,2 in similar experiments on dogs, were able to produce a decrease in minute volume of from 15-79% when the auricles were caused to fibrillate. The ventricular rate in their experiments was increased after fibrillation was induced so that the actual decrease in minute volume cannot be entirely attributed to the fibrillation of the auricles.Smith, Walker and Alt3 found that the minute volume increased approximately 30% when normal rhythm was restored by quinidine in cases of auricular fibrillation which had been previously compensated by digitalis. Realizing that in mitral stenosis auricular contraction plays an appreciable role in the filling of the left ventricle, we used only mitral stenosis cas...

Approximately 100 patients suffering from disturbed energy metabolism of the skeletal muscle mitochondria have been reported in the literature. A malfunction of the respiratory chain was found in about two-thirds of these patients. NADH dehydrogenase and cytochrome c oxidase deficiencies have been most frequently reported, but the application of improved enzymatic techniques reveals that, in many patients, the defects in the respiratory chain are not restricted to a single enzyme deficiency. In this study the biochemical findings in six patients with representative defects in the respiratory chain of their skeletal muscle mitochondria are presented. Attention is focussed on the occurrence of the multiple defects.

Physicians must keep well abreast of current developments in drug therapy to provide adequate and proper treatment of cardiac conditions. From his own experience, the author reviews the use of digitalis, rhythm-regulatory drugs, coronary dilators, cardiac stimulants, diuretics, antihypertensive agents and anticoagulants. He cautions that older therapeutic agents should not be discarded until the newer ones have been proved effective.

There have been many determinations of the “norma!” osmotic pressure of the plasma proteins of human blood, namely, Starling,1 Govaerts,2 Krogh,3 Schade,4 Verney,5 and Landis.6It is our opinion that, with the exception of Schade's determinations, there is some possibility of considerable error in all of these determinations because the determinations were made from 12 to 48 hours after taking the blood from the veins, during which time an experiment carried out by us shows that peptization of the proteins can take place, thus increasing the number of colloid particles and the colloid osmotic pressure. In some of these measurements no attempt was made to keep the temperature constant during the period of measurement and equilibration. Moreover, fluids were used on the outside of the osmometer membranes which were not exactly those of the dispersion medium. Schade7 has devised a method which we believe is accurate to 5%. It is based upon a method devised by Sorenson.8 Determinations can be made by Schade's ...

ConclusionsLowering plasma proteins to below 3% and osmotic pressure of plasma colloids to below 10 mm. produces a tendency to edema formation. The edema is very slight and does not increase rapidly until XaC1 is given, when the urinary output falls suddenly and massive edema appears.

We have determined the osmotic pressure of the plasma colloids in normal persons and in cases of glomerulonephritis with and without edema, using the method of Schade1 for the determination of the osmotic pressure of the plasma proteins at 37°C. against a collodion membrane. The normal values for the osmotic pressure of the plasma proteins were from 20 to 23 mm. Hg. The osmotic pressure of the plasma proteins was 11 mm. Hg. or lower in all our cases of nephropathic edema investigated up to the present time. Edema was not observed in cases of nephritis where the osmotic pressure of the colloids of the plasma was 17 mm. Hg. or above. Undoubtedly lowering of the osmotic pressure of the plasma proteins is a factor in the formation of edema in nephritis and nephrosis. It is best thought of as determining a “tendency to edema formation.” Other factors as ability of the kidneys to excrete water, salt retention, anoxemia and toxins altering capillary permeability, etc., contribute to the formation of edema. By re...

The pyruvate dehydrogenase complex plays a central role in the pyruvate oxidation. The complex consists of five components of which pyruvate dehydrogenase (E1) catalyzes the rate limiting step. Since E1 has a low activity in human skeletal muscle tissue a sensitive method is needed for diagnostic purposes. Measurement of 14CO2-production from [1-14C]pyruvate provides a specific and sensitive assay for measuring E1 activity in crude extracts. In the E1 assay an artificial eiectronacceptor has to be added. We use dichlorophenolindophenol (DCPIP) instead of the often applied ferricyanide. DCPIP shows no inhibitory effects on E1 activity. E1 activity appears to be dependent on the cofactors thiaminepyrophosphate and magnesium and is completely inhibited by fluoropyruvate. The method can be applied to frozen or fresh small muscle samples, obtained by needle or open biopsy. We established a difference in E1 activity between 600 g supernatant and horrogenate of skeletal muscle tissue. The measurement of E1 activity in supernatant from frozen muscle appeared to be unreliable. Control values in homogenate, 515-2080 nmol.hr−1.g−1. muscle, are higher or the same as those reported by others. With the new assay we identified two patients with a E1 deficiency. The method appears also suitable for measurement of E1 activity in chorionic villi.

Excerpt The proteins of the blood plasma being hydrophilic colloids in solution must exert an osmotic pressure. This osmotic pressure measures the momentum of the impacts made by the colloid partic...

Excerpt Numerous investigators have produced edema by a reduction of the plasma proteins. The reduction of the plasma proteins by repeated bleedings is called plasmapheresis. Leiter1,2and Barker an...