[Tumor effects on the heart and circulation]. / Effekte des Tumors auf Herz und Kreislauf.

As a result of the continuous development of modern cancer treatment, more cancer patients can be cured every year. However, since many patients experience cardiovascular problems before, during and after their cancer treatment, cardio-oncology is becoming increasingly important. Numerous therapies can cause cardiotoxicity, such as chemotherapy, immunotherapy, antibody therapy and radiotherapy. If these remain undetected, the patient may develop, e.g. heart failure or severe heart valve damage. The broad spectrum of cardiovascular comorbidities has become an immense challenge for cardiologists and oncologists. Cardio-oncology also deals with the effects that cancer has on the cardiovascular system. New research indicates that the tumor itself also has direct negative effects on the heart, mediated by messenger substances. Therefore, it is important to understand which cancer patients are at increased cardiovascular risk, thereby enabling the development of new therapeutic approaches in the long term to maintain mobility and improve patient prognosis.

Models of sarcopenia: Short review.

Approximately 40-50% of the population over 80years of age suffers from sarcopenia making this condition a major geriatric clinical disorder and a key challenge to healthy aging. The hallmark symptom of sarcopenia is the loss of muscle mass and strength without the loss of overall body weight. Sarcopenic patients are likely to have worse clinical outcomes and higher mortality compared to healthy individuals. This review will focus on animal models designed to study sarcopenia including hind-limb unloading, de-nervation, and immobilization by using casts or wire strategies, as well as using aged rodents. Currently there are no registered treatments for sarcopenia. Most sarcopenic individuals show signs of physical frailty, which leads to increases the prevalence of balance disorders, falls, fractures and pain. Therefore, is it essential to develop and use relevant animal models to further the research on sarcopenia therapy?

Novel Hairless mutations in two kindreds with autosomal recessive papular atrichia.

Papular atrichia is an autosomal recessive disorder characterized clinically by the occurrence of universal congenital alopecia and disseminated papular lesions. Recently, mutations in the human hairless (HR) gene have been reported in Irish and Arab Palestinian families with papular atrichia. We have studied two further kindreds with this clinical phenotype from other ethnic backgrounds. For mutation detection the complete coding region as well as exon-intron boundaries of the HR gene were sequenced. The first family is a Mexican family with clinically typical papular atrichia. Sequencing identified a homozygous deletion of 4 bp in exon 7 (2001delCCAG) leading to a premature stop codon in exon 8. The second family is a South Tyrolian family with affected individuals showing papular atrichia and retardation of bone age during childhood. All affected individuals were identified as homozygous for an A-->G transition at nucleotide position 2909 (exon 14) leading to an amino acid change of asparagine to serine in codon 970 (Asn970Ser). These data provide further evidence for the involvement of hairless mutations in papular atrichia. In addition, these findings suggest that the hairless protein is not only involved in hair development but also in the process of ossification during development.

The effect of misclassification error on reported cause-specific mortality fractions from verbal autopsy.

BACKGROUND: Verbal autopsy (VA) studies are important for measuring cause-specific mortality in areas where medical certification of cause of death is uncommon. This paper explores the effects of misclassification errors on the results of verbal autopsy studies, and recommends ways to take misclassification errors into account in the interpretation of results. METHODS: Mathematical formulae are derived for determining the size and direction of the error in cause-specific mortality estimates based on VA studies caused by misclassification. The levels of sensitivity and specificity found in currently available validation studies for childhood VA are examined. RESULTS: There can be substantial errors in the estimates of the cause-specific mortality fraction derived from VA studies. The cause-specific mortality fraction itself has an important influence on the size of the error for given levels of sensitivity and specificity, and when the cause-specific mortality fraction is small, the size of the error depends more on specificity than on sensitivity. CONCLUSION: Despite its drawbacks VA seems to be the most promising way of establishing cause of death when most deaths take place at home without medical attention. However, more validation studies on standardized instruments are required in order to collect information about sensitivity and specificity and subsequently improve the design of the instrument. At the same time, analysts need to take misclassification errors into consideration in ways outlined in this paper.

Relationship between the microstructure and the mechanical and barrier properties of whey protein films.

This work was focused on the relationship between the microstructure and the mechanical and barrier properties of whey protein isolate (WPI) films. Sorbitol (S) and glycerol (G) were used as plasticizers and the pH was varied between 7 and 9. The films were cast from heated aqueous solutions and dried in a climate room at 23 degrees C and 50% relative humidity for 16 h. The microstructure of the films was found to be dependent on the concentration, the plasticizers, and the pH. When the concentration increased, a more aggregated structure was formed, with a denser protein network and larger pores. This resulted in increased water vapor permeability (WVP) and decreased oxygen permeability (OP). When G was used as a plasticizer instead of S, the microstructure was different, and the moisture content and WVP approximately doubled. When the pH increased from 7 to 9, a denser protein structure was formed, the strain at break increased, and the OP decreased.

Effects of pH and the gel state on the mechanical properties, moisture contents, and glass transition temperatures of whey protein films.

The mechanical properties, moisture contents (MC), and glass transition temperature (T(g)) of whey protein isolate (WPI) films were studied at various pH values using sorbitol (S) as a plasticizer. The films were cast from heated aqueous solutions and dried in a climate chamber at 23 degrees C and 50% relative humidity (RH) for 16 h. The critical gel concentrations (c(g)) for the cooled aqueous solutions were found to be 11.7, 12.1, and 11.3% (w/w) WPI for pH 7, 8, and 9, respectively. The cooling rate influenced the c(g), in that a lower amount of WPI was needed for gelation when a slower cooling rate was applied. Both cooling rates used in this study showed a maximum in the c(g) at pH 8. The influence of the polymer network on the film properties was elucidated by varying the concentration of WPI over and under the c(g). Strain at break (epsilon(b)) showed a maximum at the c(g) for all pH values, thus implying that the most favorable structure regarding the ability of the films to stretch is formed at this concentration. Young's modulus (E) and stress at break (sigma(b)) showed a maximum at c(g) for pH 7 and 8. The MC and epsilon(b) increased when pH increased from 7 to 9, whereas T(g) decreased. Hence, T(g) values were -17, -18, and -21 degrees C for pH 7, 8, and 9, respectively. E and sigma(b) decreased and epsilon(b) and thickness increased when the surrounding RH increased. The thickness of the WPI films also increased with the concentration of WPI.

Aging of whey protein films and the effect on mechanical and barrier properties.

This work focuses on the aging of whey protein isolate (WPI) films plasticized with glycerol (G) and sorbitol (S). The films were cast from heated aqueous solutions at pH 7 and dried at 23 degrees C and 50% relative humidity (RH) for 16 h. They were stored in a climate room (23 degrees C, 50% RH) for 120 days, and the film properties were measured at regular intervals. The moisture content (MC) of the WPI/G films decreased from 22% (2 days) to 15% (45 days) and was thereafter constant at 15% (up to 120 days). This affected the mechanical properties and caused an increased stress at break (from 2.7 to 8.3 MPa), a decreased strain at break (from 33 to 4%), and an increased glass transition temperature (T(g)) (from -56 to -45 degrees C). The barrier properties were, however, unaffected, with constant water vapor permeability and a uniform film thickness. The MC of the WPI/S films was constant at approximately 9%, which gave no change in film properties.

Nodding syndrome in Mundri county, South Sudan: environmental, nutritional and infectious factors.

BACKGROUND: Nodding Syndrome is a seizure disorder of children in Mundri County, Western Equatoria, South Sudan. The disorder is reported to be spreading in South Sudan and northern Uganda. OBJECTIVE: To describe environmental, nutritional, infectious, and other factors that existed before and during the de novo 1991 appearance and subsequent increase in cases through 2001. METHODS: Household surveys, informant interviews, and case-control studies conducted in Lui town and Amadi village in 2001-2002 were supplemented in 2012 by informant interviews in Lui and Juba, South Sudan. RESULTS: Nodding Syndrome was associated with Onchocerca volvulus and Mansonella perstans infections, with food use of a variety of sorghum (serena) introduced as part of an emergency relief program, and was inversely associated with a history of measles infection. There was no evidence to suggest exposure to a manmade neurotoxic pollutant or chemical agent, other than chemically dressed seed intended for planting but used for food. Food use of cyanogenic plants was documented, and exposure to fungal contaminants could not be excluded. CONCLUSION: Nodding Syndrome in South Sudan has an unknown etiology. Further research is recommended on the association of Nodding Syndrome with onchocerciasis/mansonelliasis and neurotoxins in plant materials used for food.

Clinical and epidemiologic characteristics of nodding syndrome in Mundri County, southern Sudan.

BACKGROUND: Nodding syndrome (repetitive nodding and progressive generalized seizures) is assuming epidemic proportions in South Sudan, Tanzania and Uganda. OBJECTIVE: To describe clinical and epidemiological features of nodding syndrome in southern Sudan based on preliminary investigations conducted in 2001 and 2002. METHOD: Household surveys, clinical, electrophysiological (EEG) assessments, informant interviews and case-control studies were conducted in the town of Lui and the village of Amadi in southern Sudan. RESULTS: Nodding syndrome is characterized by involuntary repetitive nodding of the head, progressing to generalized seizures; mental and physical deterioration. The EEGs were consistent with progressive epileptic encephalopathy. Prevalence of Nodding syndrome in Lui and Amadi was 2.3% and 6.7% respectively. All case control studies showed a positive association between cases and Onchocerca volvulus. A history of measles was negatively associated with being a case: 2/13 of cases and 11/19 of controls had had measles: odds ratio 0.13 (95% CI 0.02, 0.76). Environmental assessment did not reveal any naturally occurring or manmade neurotoxic factors to explain Nodding Syndrome, although fungal contamination of food could not be ruled out. CONCLUSION: Nodding Syndrome was strongly associated with Onchocerca volvulus. There was no evidence to suggest an environmental pollutant, chemical agent, or other toxic factor.

Treatment patterns for childhood diarrhoea: evidence from demographic and health surveys.

Treatment patterns for childhood diarrhoea among providers in public and private settings have been examined using data from 28 surveys in the Demographic and Health Surveys programme. In the majority of surveys, at least 50% of the children with diarrhoea who sought care from a health provider (public or private) received treatment that included oral rehydration salts (ORS). Private providers are a significant source of care for children with diarrhoea, but they are less likely to use ORS and more likely to prescribe unneeded drugs than providers in public settings. In countries where data are available, bloody diarrhoea appears to be undertreated. The results indicate that national public health programmes must continue to improve their strategies to ensure correct treatment of childhood diarrhoea by all health providers.

A method for meta-analysis where the level of data aggregation differs between studies.

BACKGROUND: This paper presents a statistical method that was used to assess haemoglobin levels world-wide among women, based on a combination of over 400 studies. METHODS: The methodology is easy to implement and is specifically adapted to the case where mean observations are taken, although the subgroups represented by the mean values may differ from study to study. That is, the level of data aggregation is not consistent between studies. RESULTS: In this example some studies report average haemoglobin levels for a sample of the population, while others give averages by urban/rural classification and/or pregnancy status. Though the method is based on likelihood principles, computation is straightforward. CONCLUSIONS: The methodology can be applied to a variety of meta-analytic situations where assessments are based on combining data from several sources. We provide an example of how the method was implemented in a study of haemoglobin levels among women undertaken at the World Health Organisation.

The use of focus groups in social and behavioural research: some methodological issues.

The use of focus groups as a qualitative method for rapid assessment is discussed. A focus-group session is an in-depth discussion in which a small number of people (usually 8-12) from the target population discuss topics that are of importance for a particular study or project. Generally the participants are chosen purposively, and it is recommended that they should be homogeneous with respect to characteristics which might otherwise impede the free flow of discussion. Focus groups can be used for idea generation, in conjunction with a quantitative method, or as a primary data-collection method. However, if focus groups are used as a primary data-collection method, their results must be treated with caution. The main advantage of using focus-group discussions during rapid assessment is that they provide in-depth information without requiring full-scale anthropological investigations. The informal group setting is believed to make people feel at ease, encouraging them to express their views freely. However, there are a number of limitations to focus-group discussions. The samples are small and purposively selected, and therefore do not allow generalization to larger populations. In addition, as with other qualitative methods, the chances of introducing bias and subjectivity into the interpretation of the data are high. There are a number of methodological issues which still need to be addressed in order to further develop the method. Little is known about how many discussion sessions are needed to be reasonably sure that most aspects related to the subject of inquiry have been explored.(ABSTRACT TRUNCATED AT 250 WORDS)

Rapid evaluation methods (REM) of health services performance: methodological observations.

The rapid evaluation method (REM) was developed by WHO in order to assess the performance and quality of health care services, identify operational problems, and assist in taking managerial action. It was tested in five developing countries (Botswana, Madagascar, Papua New Guinea, Uganda and Zambia) between 1988 and 1991. REM consists of a set of observation- and survey-based diagnostic activities, carried out mainly in health care facilities. The article describes the various steps of REM, methodological issues such as setting objectives and using an issue-information matrix, preparation of survey instruments, use of computer software (Epi Info), data quality control, fieldwork, and the use of data to produce useful information for decision-makers. REM aims at bringing prompt and relevant information to planners and decision-makers who need it for a specific purpose. In the present examples, REM provided information for preparing a programme proposal for external funding, for establishing baseline data for a situation analysis, and for assessing staff performance after extensive training in order to improve the curriculum.

PIP: The rapid evaluation method (REM) is a health management tool aimed at bringing prompt an relevant information to planners and decision makers. The method was developed by WHO's Family Health Division and was field tested in mother and child health care and family planning facilities in Botswana, Madagascar, Papua New Guinea, Uganda, and Zambia between 1988 and 1991. The purpose of this paper is to acquaint the reader with the basic components of the method and methodological problems that arise. Each of the data collection instruments employed is described: clinic exit interviews, health staff interviews, observation of task performance, community and staff focus group discussions, review of clinical records, checking of facilities and equipment and supplies, and household interviews. REM was developed because of the apparent problems of too much paperwork and insufficient time for useful analysis and fears of the expense of surveys. There was a need for a quick, accurate, and economical method of evaluation of facilities and client satisfaction. Reference is made to other REM approaches and a review of REM methods. A basic requirement is the involvement of national program managers in the control, implementation, and application of the design; outside consultants furnish information on methods, formats, and analytical techniques as a complement to national efforts. THe first action taken is to define the objectives and specify the topics and issues of concern. A core group is assigned responsibility for REM. The action plan involves the objectives, information desired, sources for information, schedule of activities, logistical arrangements, and budget preparation. The level of detail of the information desired is defined by the core group and its objectives. A matrix of information is developed which includes information requested and sources; an example is provided. The results of the 5-county evaluation revealed methodological concern about the identification of issues and pretesting of instruments, data quality control, advance notice and planning of fieldwork, the need for analysts familiar with Epi Info Software, analysis of quantitative data first and training of leaders for focus groups, and the need for basic results in 7-10 days and a draft report in several weeks.

Symptom profiles of psychiatric disorders based on graded disease classes: an illustration using data from the WHO International Pilot Study of Schizophrenia.

The Grade of Membership (GoM) model is a classification procedure which allows a person to be a member of more than one diagnostic class. It simultaneously quantifies the degrees of membership in classes while generating the discrete symptom profiles or 'pure types' describing classes. The model was applied to the symptomatology, history, and follow-up of 1065 cases in the WHO International Pilot Study of Schizophrenia. The model produced an eight diagnostic class or 'pure type' solution, of which five were related to the diagnostic concepts of schizophrenia and paranoid disorder, two types were affective disorders, and one asymptomatic type. A subtype of paranoid schizophreniform disorder found primarily in developing countries was identified. There was a strong association between pure types and the original clinical and computer generated (CATEGO) diagnoses. A GoM based psychiatric classification might more clearly identify core disease processes than conventional classification models by filtering the confounding effects of individual heterogeneity from pure type definitions.

Early manifestations and first-contact incidence of schizophrenia in different cultures. A preliminary report on the initial evaluation phase of the WHO Collaborative Study on determinants of outcome of severe mental disorders.

In a context of a WHO collaborative study, 12 research centres in 10 countries monitored geographically defined populations over 2 years to identify individuals making a first-in-lifetime contact with any type of 'helping agency' because of symptoms of psychotic illness. A total of 1379 persons who met specified inclusion criteria for schizophrenia and other related non-affective disorders were examined extensively, using standardized instruments, on entry into the study and on two consecutive follow-ups at annual intervals. Patients in different cultures, meeting the ICD and CATEGO criteria for schizophrenia, were remarkably similar in their symptom profiles and 49% of them presented the central schizophrenic conditions as defined by CATEGO class S+. However, the 2-year pattern of course was considerably more favourable in patients in developing countries compared with patients in developed countries, and the difference could not be fully explained by the higher frequency of acute onsets among the former. Age- and sex-specific incidence rates and estimates of disease expectancy were determined for a 'broad' diagnostic group of schizophrenic illness and for CATEGO S+ cases. While the former showed significant differences among the centres, the differences in the rates for S+ cases were non-significant or marginal. The results provide strong support for the notion that schizophrenic illnesses occur with comparable frequency in different populations and support earlier findings that the prognosis is better in less industrialized societies.

The lot quality technique: a global review of applications in the assessment of health services and disease surveillance.

Since the mid-1980s, there has been growing interest in adapting the lot quality (LQ) technique to monitor the quality of health care services, especially in developing countries. This global review has identified a total of 34 LQ surveys conducted from 1984 to 1996 in Africa, the Americas, Europe, South-East Asia, and the Western Pacific. Health care parameters assessed in the surveys varied and some surveys assessed more than 1 health parameter: 24 surveys assessed immunization coverage, 9 examined women's health issues such as family planning and antenatal care, 5 assessed use of oral rehydration therapy, 5 estimated disease incidence, and 3 others evaluated health worker performance. These studies indicate that LQ is a practical, relatively low-cost field method which is increasingly being applied in health programmes.

A distinct gene close to the hairless locus on chromosome 8p underlies hereditary Marie Unna type hypotrichosis in a German family.

BACKGROUND: Hypotrichosis of the Marie Unna type (HMU) is a rare autosomal dominant disorder characterized by male-pattern hair loss with childhood onset and anomalies of the hair shaft. OBJECTIVES: We aimed to evaluate a number of chromosomal loci as possible candidate regions for HMU. METHODS: A linkage analysis was performed in a large German family using microsatellite markers spanning candidate regions on chromosomes 8, 12 and 17. RESULTS: We found that the HMU locus maps to chromosomal region 8p21 in a 13.01-cM interval between markers D8S1145 and D8S1771. This interval harbours the hairless gene (HR). Mutational analysis of HR on the genomic and transcript levels revealed no pathogenic mutation. CONCLUSIONS: Our findings, together with a recent report of two unrelated families of Dutch and British origin, provide evidence for a hair growth regulatory gene distinct from HR in chromosomal region 8p21.

Cloning, genomic organization, alternative transcripts and mutational analysis of the gene responsible for autosomal recessive universal congenital alopecia.

Complete or partial congenital absence of hair (congenital alopecia) may occur isolated or with associated defects. The majority of families with isolated congenital alopecia has been reported to follow an autosomal recessive mode of inheritance (MIM 203655). We have previously mapped the gene for autosomal recessive congenital alopecia in a large inbred Pakistani family in which affected persons show complete absence of hair development (universal congenital alopecia) to a 15 cM region on chromosome 8p21-22. Here we report the cloning and characterization of the human homologue of the mouse hairless gene and show that it is located in the critical region on chromosome 8p21-22. Determining the exon-intron structure allowed detailed mutational analysis of DNA samples of patients with universal congenital alopecia. We detected a homozygous missense mutation in the Pakistani family and a homozygous splice donor mutation in a family from Oman. In addition, we show that the human hairless gene undergoes alternative splicing and that at least two isoforms generated by alternative usage of exon 17 are found in human tissues. Interestingly, the isoform containing exon 17 is the predominantly expressed isoform in all tissues but skin, where exclusive expression of the shorter isoform was observed. We speculate that this tissue-specific difference in the proportion of hairless transcripts lacking exon 17 sequences could contribute to the tissue-specific disease phenotype observed in individuals with isolated congenital alopecia.