D-Galacturonic acid reduction by S. cerevisiae for L-galactonate production from extracted sugar beet press pulp hydrolysate.

Pectin-rich residues are considered as promising feedstocks for sustainable production of platform chemicals. Enzymatic hydrolysis of extracted sugar beet press pulp (SBPP) releases the main constituent of pectin, D-galacturonic acid (D-GalA). Using engineered Saccharomyces cerevisiae, D-GalA is then reduced to L-galactonate (L-GalOA) with sorbitol as co-substrate. The current work addresses the combination of enzymatic hydrolysis of pectin in SBPP with a consecutive optimized biotransformation of the released D-GalA to L-GalOA in simple batch processes in stirred-tank bioreactors. Process conditions were first identified with synthetic media, where a product concentration of 9.9 g L-1 L-GalOA was obtained with a product selectivity of 99% (L-GalOA D-GalA-1) at pH 5 with 4% (w/v) sorbitol within 48 h. A very similar batch process performance with a product selectivity of 97% was achieved with potassium citrate buffered SBPP hydrolysate, demonstrating for the first time direct production of L-GalOA from hydrolyzed biomass using engineered S. cerevisiae. Combining the hydrolysis process of extracted SBPP and the biotransformation process with engineered S. cerevisiae paves the way towards repurposing pectin-rich residues as substrates for value-added chemicals. KEY POINTS: • Efficient bioreduction of D-GalA with S. cerevisiae in stirred-tank reactors • Batch production of L-GalOA by engineered S. cerevisiae with high selectivity • Direct L-GalOA production from hydrolyzed sugar beet press pulp Bioreduction of D-galacturonic acid to L-galactonate with recombinant Saccharomyces cerevisiae enables for the first time the valorization of hydrolysates from extracted sugar beet press pulp for the sustainable production of value-added chemicals.

Development and Suggestion of a Cardiac CTA Scoring System for the Prediction of Revascularization Success in Chronic Total Occlusions (CTO) of the Coronary Arteries.

OBJECTIVE: Analyzing occluded segments with computed tomography angiography (CTA) prior to percutaneous coronary intervention (PCI) increased revascularization success in chronic total occlusions (CTO). The aim of our study was to develop a scoring system for the prediction of PCI success in CTO. MATERIALS AND METHODS: 41 consecutive CTO patients (30 male; 63.1 years +/- 8.3 standard deviation) underwent CTA prior to PCI. All CTOs were categorized by two radiologists in consensus regarding the presence of special features and without knowledge of PCI outcome. All outcome criteria were evaluated. Afterwards one point was assigned for each unequally distributed outcome criteria per CTO and all points were added up to a single score. RESULTS: Severe calcifications (failure group 68.8 % vs. success group 28.0 %; p < 0.02) and intraluminal calcifications (68.8 %; 40.0 %), tortuosity (25.0 %; 0 %; p < 0.02), linear intrathrombus enhancement (37.5 %; 60.0 %) and distal vessel disease (68.8 %; 44.0 %) were unequally distributed. By adopting a threshold of 4 points or higher (maximum 5 points), the results were: sensitivity 31.3 %, specificity 100 %, negative predictive value (NPV) 69.4 % and positive predictive value (PPV) 100 %. The PCI complication rate was 9.8 % and the mean contrast media amount was 234.4 ml. CONCLUSION: With the suggested scoring system, based on five CTA criteria, PCI failure could be predicted with high PPV and specificity in our group of patients, but the NPV and sensitivity are low. However, 5 unsuccessful PCIs (13.2 %) could have been avoided and none would have been wrongly omitted. Regarding the complication rate during PCI and the high amounts of contrast media needed, a prediction system appears to be desirable and should be the object of large-scale trials. KEY POINTS: Single predictors of revascularization success in CTO have been identified. Success rates are improved by analyzing CTA data sets prior to revascularization approaches. Prediction of revascularization success via a scoring system based on five CTA criteria seems promising. Patient selection for the right treatment options might be improved in the future due to application of the scoring system. Also risks, complications, contrast media amounts and radiation doses might be reduced.

T1, T2 Mapping and Extracellular Volume Fraction (ECV): Application, Value and Further Perspectives in Myocardial Inflammation and Cardiomyopathies.

UNLABELLED: Cardiac magnetic resonance imaging (CMRI) is a versatile diagnostic tool. One of its main advantages is the possibility of tissue characterization. T1-weighted images for scar and T2-weighted images for edema visualization are key methods for tissue characterization. Otherwise these sequences are strongly limited for the detection of diffuse myocardial pathologies. Recently, rapid technical innovations have generated new techniques. T1, T2 mapping and evaluation of the extracellular volume fraction (ECV) allow quantification of diffuse myocardial pathologies and showed great potential in the visualization of fibrosis, edema, amyloid, iron overload and lipid. In the future these techniques might enable the detection of early cardiac involvement, even act as a prognosticator. Moreover, therapy monitoring and follow-up might be possible due to versatile parameter quantification with these new techniques. KEY POINTS: CMR allows for tissue characterization via T1- and T2-weighted sequences. In cases of diffuse, global myocardial pathologies, correct image interpretation with traditional CMR sequences might be difficult. T1, T2 mapping and ECV can quantify diffuse, global myocardial pathologies. Alterations of myocardial T1 and T2 relaxation times occur in various myocardial diseases (e.g. acute myocarditis). In the future mapping might act as a prognosticator or therapy monitoring tool.

Extramammary Paget's Disease : Case Report of a Penoscrotal Presentation.

We report the case of a 72 year old male with penoscrotal extramammary Paget's disease (EMPD). The patient presented with an eczematous lesion on the scrotum extending on to the base of the penis. Given the persistent and progressive nature of the lesion a biopsy was taken which revealed a malignant lesion suggestive of extramammary Paget's disease. After performing a CAT-scan of the lower abdomen and inguinal region, which was negative, a primary surgical approach with curative intentions was taken. One year after surgery the patient is doing well and shows no sign of local recurrence.

[Informant report of cognitive changes in the elderly. A first evaluation of the German version of the IQCODE]. / Fremdbeurteilung kognitiver Veränderungen im Alter. Erste Vergleichswerte für den deutschen IQCODE.

BACKGROUND: Cognitive deficits occurring with dementia are frequently not reported by the affected subject. Therefore, informant reports from close relatives are especially important for the early diagnosis of dementia. Internationally, the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) has been evaluated with positive results and is a widely used informant-rated instrument for the diagnosis of cognitive decline. For the German speaking countries, norms and evaluation of the psychometric properties of the instrument are lacking. METHODS: Norms for the German long version of the IQCODE were established with 46 healthy elderly married couples. These were compared with respect to their concurrent and discriminative validity with groups of patients suffering from mild cognitive impairment (MCI, n=25), Alzheimer's or mixed dementia (AD, n=59) and frontotemporal lobe degeneration (FTLD, n=15). RESULTS: The German version of the IQCODE exhibited good psychometric properties and was able to best discriminate between cognitively intact and demented subjects with AD. Receiver-operating characteristic analyses indicated a cut-off score of 3.38 which corresponds well with the value given in international literature. Patients with MCI and with FTLD were also reliably distinguished from cognitively intact subjects. However, the instrument did not distinguish AD from FTLD with any significant degree of confidence. DISCUSSION: The German version of the IQCODE reliably discriminates cognitively intact persons from those suffering from MCI or cortical dementia, but not between different types of cortical dementia, such as AD and FTLD. The IQCODE is an efficient informant-rated screening instrument for the early diagnosis of cognitive decline and dementia.

[Evidence based treatment of executive dysfunction]. / Evidenzbasierte Therapie bei exekutiver Dysfunktion.

The therapy of executive functions plays an essential role for the functional outcome and the social reintegration. Nevertheless there is a lack of cognitive oriented and evidence-based therapy programs. The purpose of our review is the classification of the present evaluation studies with regard of the principles of evidence based medicine (EbM) and of the content. Besides the EbM criteria the number of participants, the kind and number of interventions, the types of etiology and the standardisation and quality of the outcome parameters are measured. By that, an assessment should be possible, which interventions are successful for what types of dysexecutive syndrome. The present studies belong to three different types of therapy: at first, a therapy form focussing on manipulation and modification of the environment, second, a therapy form using behaviour management and a third form, which is based on practise and cognitive interventions. The heterogeneity of the therapy forms makes different types of evaluation necessary. The evaluation studies reach different classes of evidence. While the cognitive therapy forms reach comparable high evidence classes, the evaluation studies about behaviour management--mostly present as single case studies with individual outcome parameter--reach only low evidence classes. Final, we discuss, which therapy forms are effective using the strong evaluation criteria and at which point further conceptual task and further research is useful.

Parental perceptions and attitudes about informed consent in clinical research involving children.

We interviewed 64 parents by questionnaire after completion of a clinical trial involving their children for their perceptions and attitudes about informed consent. The results show that only a small minority realized that drug trials are designed to assess not only efficacy but safety as well. More worrisome was the majority of parents who felt that drug trials conducted by hospitals are of no or low risks. Moreover, a significant minority offered the view that the strict informed consent procedures we followed were unnecessary because they would do what the doctor advised. Even more worrisome was the small percentage of parents who realized that a signed consent form was primarily meant to protect their rights, and only one-third of the parents knew of their right to withdraw their child unconditionally from the trial at any time. These findings suggest that there may be significant attitudinal barriers to parental understanding of the informed consent process.

Aftercare for participants in clinical research: ethical considerations in an asthma drug trial.

The issue of aftercare for participants in clinical research was explored in the context of an asthma drug trial. Although there may be financial constraints and practical difficulties with implementation, the results show that it may be feasible for clinical investigators and commercial sponsors to take on some limited responsibility for the medical care of research subjects after clinical trials. However, the ethical implications for this practice remain unclear. On the one hand, society may have a moral obligation to compensate and reward some of its members who assume the risk of research subjects for the benefit of society as a whole. On the other hand, the promise of aftercare may provide an inducement to volunteers which, under certain conditions may be considered morally wrong and scientifically unsound.

Parental perceptions and attitudes about informed consent in clinical research involving children.

We interviewed 64 parents by questionnaire after completion of a clinical trial involving their children for their perceptions and attitudes about informed consent. The results show that only a small minority realised that drug trials are designed to assess not only efficacy but safety as well. More worrisome was the majority of parents who felt that drug trials conducted by hospitals are of no or low risks. Moreover, a significant minority offered the view that the strict informed consent procedures we followed were unnecessary because they would do what the doctor advised. Even more worrisome was the small percentage of parents who realised that a signed consent form was primarily meant to protect their rights, and only one-third of the parents knew of their right to withdraw their child unconditionally from the trial at any time. These findings suggest that there may be significant attitudinal barriers to parental understanding of the informed consent process.

A multicentre randomized placebo-controlled double-blind study on the efficacy of Ketotifen in infants with chronic cough or wheeze.

The efficacy of Ketotifen was examined in the treatment of 113 infants between 6 and 36 months of age presenting with a history of cough and/or wheeze in a multicentre randomized placebo-controlled double-blind study. A 4 week no-medication baseline phase preceded the 16 week treatment phase in which infants took 2.5 mL twice daily of either placebo or Ketotifen (0.5 mg) syrup; this was followed by a 4 week wash-out phase. Diary card evaluation was performed by the parent or guardian for the duration of the study and recorded wheeze and cough twice daily as well as medication used. The percentage of symptom-free days decreased significantly in both groups (P < 0.005) with placebo-treated infants experiencing significantly more symptom-free days compared with the Ketotifen group (P < 0.01), although this difference was never more than 10% in any 4 week treatment period. Symptom severity scores and use of beta-agonist medication were also less in the placebo-treated infants but did not reach statistical significance. This study was unable to show a therapeutic advantage of Ketotifen over placebo in this group of infants with chronic cough and/or wheeze and the apparent statistical advantage of placebo is not a clinically relevant finding.

The quality of student-tutor interactions in the clinical learning environment.

We surveyed 403 students in their clinical years for their perceptions of the quality of clinical clerkships. Between 42.6 and 67.0% of tutorials were said to contain positive factors such as a relaxed teaching atmosphere, enthusiasm, a good selection of patients and adequate preparation. Negative features in 18.2-37.2% of tutorials included unreasonable expectations, conflicting information, late arrival, early departure, failure to show up and the display of anger, a patronizing attitude, favouritism or ridicule. While two-thirds of tutors were regarded as friendly and helpful, the remaining one-third were perceived as unconcerned, discouraging, derogatory or hostile. Overall, only half the clinical tutors were rated as effective teachers; more specifically in medicine and psychiatry, less than one-third of consultants were regarded as effective teachers, as compared with some two-thirds of consultants in obstetrics and gynaecology and paediatrics who were so regarded. Almost two-thirds of the students had predominantly positive reactions to interactions with their tutors, in terms of being motivated to learn, enthused about the subject and having their self-confidence increased. Some one-quarter had negative reactions such as indifference, depression, anger, embarrassment and fearfulness. However, the impact of student-tutor interactions was mainly confined to the students' academic well-being, with little effect on their personal-social lives. Finally, one-third of students had experienced at least some form of mistreatment by their tutors, including gender, appearance, religious and racial discrimination, unfair grading and public humiliation. These findings suggest that the clinical clerkship may not be providing an optimal learning environment for medical students.

Elastofibroma dorsi: CT, MR and pathologic study in a new case.

As reported before elastofibroma dorsi is a rare benign tumor of elastic connective tissue with typical clinical and suggestive radiological features. We evaluated the CT and MR characteristics of this periscapular lesion in a new case, before and after contrast enhancement, and tried to determine in how far the nature and extent of the tumor can be predicted.

The psychological profile of parents who volunteer their children for clinical research: a controlled study.

Three standard psychometric tests were administered to parents who volunteered their children for a randomised, double-blind placebo-controlled trial of a new asthma drug and to a control group of parents whose children were eligible for the trial but had declined the invitation. The trial took place at a children's hospital in Australia. The subjects comprised 68 parents who had volunteered their children and 42 who had not, a participation rate of 94 per cent and 70 per cent, respectively. The responses of these parents to the Gordon Survey of Interpersonal Values Questionnaire, the Coopersmith Self-Esteem Inventory and the Cattell Sixteen Personality Factor Questionnaire were analysed by computer. There was a marked difference between the psychological profiles of the two groups of parents. Volunteering parents put more value on benevolence while non-volunteering parents were more concerned with power and prestige. The self-esteem of volunteering parents was much lower than that of non-volunteering parents. Finally, volunteering parents were more introverted, exhibited greater anxiety and low supergo, while non-volunteering parents appeared to have greater social confidence and emotional stability. Since an individual's values, self-esteem and personality may be important antecedents of behaviour, these findings suggest that parents who volunteer their children for clinical research are not only socially disadvantaged and emotionally vulnerable, but may also be psychologically predisposed to volunteering. Furthermore, these findings provide evidence for the existence of a psychosocial 'filter' effect of the informed consent procedure, which may be discouraging the better educated, more privileged and psychologically resilient members of society from participation as research subjects.

Molecular structure of the multifunctional fatty acid synthetase gene of Brevibacterium ammoniagenes: its sequence of catalytic domains is formally consistent with a head-to-tail fusion of the two yeast genes FAS1 and FAS2.

The Brevibacterium ammoniagenes fatty acid synthetase (FAS) gene was isolated from a series of overlapping clones by both immunological and plaque hybridization screening of two independent gene libraries. From the isolated DNA a contiguous segment of 10,549 bp was sequenced in both directions. The sequenced DNA contained a very long (9312 nucleotides) open reading frame coding for a protein of 3104 amino acids and with a molecular mass of 327,466 daltons. Based on characteristic sequence motifs known from other FAS systems, seven different FAS active centres were identified at distinct locations within the polypeptide chain. Only one component enzyme, the 3-hydroxydecanoyl beta, gamma-dehydratase, has not yet been localized definitively within the gene. Translation is presumed to start from a GUG triplet located 25 nucleotides downstream of the transcriptional initiation site. There is a canonical Shine-Dalgarno sequence just before this start codon. Comparison of the B. ammoniagenes FAS sequence with those of other known fatty acid synthetases revealed a particularly high degree of similarity to the products of the two yeast genes, FAS1 and FAS2 (30% identical and 46% identical plus closely related amino acids). This similarity extends over the entire length of the genes and involves not only the primary sequences of individual component enzymes but also their sequential order within the multifunctional proteins. These data, together with those on the structure of other fatty acid synthetases, are interpreted in terms of a contribution of both primary structure and subunit cooperation to a conserved topology of functional domains common to all type I FAS complexes.

Preventive dental health practices of non-institutionalized Down syndrome children: a controlled study.

Although Down syndrome children are known to be greatly predisposed to periodontal disease when compared with normal children, the preventive dental health practices of non-institutionalized Down syndrome children have not been well reported. This questionnaire study of 25 Down syndrome children aged 1-14 years compared with 25 normal control children showed that Down syndrome children have poorer dental health practices compared with normal children. Significantly greater numbers of Down syndrome children were weaned from the bottle at greater than 18 months of age (56% vs 24%, p less than 0.05) or had taken a bottle to bed (40% vs 12%, p less than 0.05), indicating their increased risk for the development of nursing bottle caries. In addition, Down syndrome children were receiving less help during tooth brushing (60% vs 84%, p less than 0.05), were older when they first visited the dentist, and less likely to be taking regular fluoride supplements. These results indicate that Down syndrome children are further disadvantaged by poor preventive dental health practices and should be targeted for increased preventive dental care.

Mature-age entrants to medical school: a controlled study of sociodemographic characteristics, career choice and job satisfaction.

A comparison of 121 mature-age and 270 normal-age entrants who graduated from the University of Queensland Medical School between 1972 and 1987 shows that mature-age entrants are some 7 years older, are more likely to come from public (state) schools and less likely to have parents in professional/technical occupations. Otherwise, the two groups were similar in terms of gender, marital status, number of children, ethnic background and current practice location. The educational background of mature-age entrants prior to admission includes 44.6% with degrees in health-science areas and 31.4% with degrees in non-health areas. Reasons for delayed entry of mature-age entrants include late consideration of medicine as a career (34.7%), financial problems (31.4%), dissatisfaction with previous career (30.6%), poor academic results (19.8%), or a combination of the above factors. Motivations to study medicine include family influences (more so in normal-age entrants), altruistic reasons (more so in mature-age entrants) and a variety of personal/social factors such as intellectual satisfaction, prestige and financial security (similar for both groups) and parental expectations (more so in normal-age entrants). Mature-age entrants experienced greater stress throughout the medical course, especially with regard to financial difficulties, loneliness/isolation from the students and family problems (a greater proportion were married with children). While whole-course grades were similar in both groups, normal-age entrants tended to win more undergraduate honours/prizes and postgraduate diplomas/degrees, including specialist qualifications. Practice settings were similar in terms of group private practice, hospital/clinic practice or medical administration, but there was a greater proportion of mature-age entrants in solo private practice, and a smaller proportion in teaching/research. If given the time over, some two-thirds of both groups would choose medicine as a career. Reasons for job satisfaction include helping patients, intellectual stimulation and financial rewards. Reasons for dissatisfaction include pressure of work, red-tape/paperwork, 'doctor-bashing', long working hours, emotional strain, financial pressure, unfulfilled career expectations and irritation with trivial medical complaints.

Immunoglobulin G subclass deficiency and predisposition to infection in Down's syndrome.

Serum immunoglobulins and IgG subclasses were measured in 26 children with Down's syndrome using an enzyme-linked immunosorbent assay and monoclonal antibodies. Eighteen (69%) of the children had increased susceptibility to infection. None of the children had deficiencies of total IgG and IgM, and only one had an IgA deficiency. IgG4 deficiency was diagnosed in 14 (54%) children. One child had a deficiency of IgG2. There were no children with deficiencies of either IgG1 or IgG3. There was a significant correlation between IgG subclass deficiency and predisposition to infection (P less than 0.05). Ninety percent of the patients with severe infections had low IgG4 whereas only 25% of those with no infections had low concentrations of IgG4. These results suggest that it is important to screen patients with Down's syndrome who have frequent systemic or respiratory infections for IgG subclass deficiencies because this may not be apparent from the assay of total IgG.

[Renal autotransplantation]. / Renale autotransplantatie.

The progress of renal transplantation in the last 2 decades has made possible the development of autotransplantation and extracorporeal surgery of the kidney. By those techniques, it is possible to operate upon patients in which conservative conventional surgery is impossible. In this article the technique is described, and two typical cases are reported. The mean indications are renal vascular hypertension, malignant tumors of the kidney, traumatic lesions of the kidney and ureteral lesions. All these indications are described in detail.