Biomedical subjects
Publications and source records attributed to A Schulze.
Owing to the growing use of ultrasound in the head and neck and to technical progress, the number of tumours diagnosed in the thyroid region is increasing. The rare differential diagnosis of multiple endocrine neoplasm type 1 in a case with a unilateral intrathyroidal lump and two lumps located dorsal to the contralateral thyroid is discussed.
Prospective observation in a neonate with guanidinoacetate methyltransferase deficiency (GAMT-D), a severe neurometabolic disorder, revealed increased guanidinoacetate levels at birth. After 14-month treatment with creatine, high-dose ornithine, benzoate, and an arginine-restricted diet, the patient's development is normal and she does not present any symptoms of GAMT-D. The authors' observation indicates that early detection of GAMT-D is possible in the neonatal period, and presymptomatic treatment may prevent its manifestation.
BACKGROUND: Guanidinoactetate methyltransferase (GAMT) deficiency is an autosomal recessive disorder of creatine synthesis. The authors analyzed clinical, biochemical, and molecular findings in 27 patients. METHODS: The authors collected data from questionnaires and literature reports. A score including degree of intellectual disability, epileptic seizures, and movement disorder was developed and used to classify clinical phenotype as severe, moderate, or mild. Score and biochemical data were assessed before and during treatment with oral creatine substitution alone or with additional dietary arginine restriction and ornithine supplementation. RESULTS: Intellectual disability, epileptic seizures, guanidinoacetate accumulation in body fluids, and deficiency of brain creatine were common in all 27 patients. Twelve patients had severe, 12 patients had moderate, and three patients had mild clinical phenotype. Twenty-one of 27 (78%) patients had severe intellectual disability (estimated IQ 20 to 34). There was no obvious correlation between severity of the clinical phenotype, guanidinoacetate accumulation in body fluids, and GAMT mutations. Treatment resulted in almost normalized cerebral creatine levels, reduced guanidinoacetate accumulation, and in improvement of epilepsy and movement disorder, whereas the degree of intellectual disability remained unchanged. CONCLUSION: Guanidinoactetate methyltransferase deficiency should be considered in patients with unexplained intellectual disability, and urinary guanidinoacetate should be determined as an initial diagnostic approach.
This paper reports the third proven human case of deficient S-adenosylhomocysteine (AdoHcy) hydrolase activity. The patient is similar to the only two previously reported cases with this disorder in having severe myopathy, developmental delay, elevated serum creatine kinase (CK) concentrations, and hypermethioninaemia. Although he has been followed from infancy, the basic enzyme deficiency was established only at age 26 years. The diagnosis was based on markedly elevated plasma concentrations of both AdoHcy and S-adenosylmethionine, some 20% of the mean control activity of AdoHcy hydrolase activity in haemolysates of his red-blood cells, and two missense mutations in his gene encoding AdoHcy hydrolase. He had low values of erythrocyte phosphatidylcholine and plasma free choline and marginally elevated excretion of guanidinoacetate, suggesting that the elevated AdoHcy may have been inhibiting methylation of phosphatidylethanolamine and guanidinoacetate. His leukocyte DNA was globally more methylated than the DNA's of his parents or the mean extent of methylation measured in age-matched control subjects.
Fumarase (FH) deficiency is a rare autosomal recessive disease of the Krebs cycle causing severe neurological impairment in early childhood, characterized by encephalopathy with seizures and muscular hypotonia. Only a handful of patients with various recessive mutations in the FH gene have been described so far. Interestingly, autosomal dominant mutations in the same gene are associated with hereditary leiomyomatosis and renal cell cancer (HLRCC). We investigated a boy with developmental and growth delay, microcephaly, and muscular hypotonia recognized at the age of 3 months. No leiomyomatosis or renal cancer is known in the parents. Investigation of the patient's urine revealed massive fumarate excretion. FH activity was severely reduced in muscle and fibroblasts. Respirometric investigation of fibroblasts showed only modest changes indicating that fumarate mediated inhibition of enzymatic pathways other than oxidative phosphorylation might be more relevant in pathophysiology of FH deficiency. Molecular analysis revealed a known 435insK mutation on the paternal allele and a novel H275L mutation due to an A to T transversion of nucleotide 824 on the maternal allele. This mutation affects the same codon as a C to T transition of nucleotide 823, resulting in a H275Y mutation that was found in two families with HLRCC.
PURPOSE: This randomized phase III study compared bendamustine and prednisone (BP) to standard melphalan and prednisone (MP) treatment in previously untreated patients with multiple Myeloma (MM). PATIENTS AND METHODS: To be included, patients had to have histologically and cytologically proven stage II with progressive diseases or stage III MM. They were randomly assigned to receive BP (n=68) or MP (n=63). The primary endpoint was the time to treatment failure (TTF). Secondary endpoints included survival, remission rate, toxicity and quality of life. RESULTS: The overall response rate was 75% in the BP and 70% in the MP group. A significantly higher number of patients treated with BP achieved a complete remission than did patients receiving MP (32 vs. 13%; P=0.007), and the maximum response was achieved more rapidly in patients treated with BP compared to those receiving MP (6.8 vs. 8.7 cycles; P<0.02). TTF and remission duration were significantly longer in the BP group. Patients receiving BP had higher QoL scores and reported pain less frequently than patients receiving MP. CONCLUSION: BP is superior to MP with respect to complete remission rate, TTF, cycles needed to achieve maximum remission and quality of life and should be considered the new standard in first-line treatment of MM patients not eligible for transplantation.
UNLABELLED: "Tobacco control" is one of six health targets of the forum gesundheitsziele.de (health targets). Key stakeholders from health policy and from the health system are involved in the process of defining and deciding about health targets. The goal of gesundheitsziele.de is the improvement of the health of the population through integrated action. Goals are supplemented with recommendations for intervention measures, and indicators to mea sure whether goals had been achieved. The evaluation board of gesundheitsziele.de is committed to assess the availability and appropriateness of German data bases for the evaluation of the health target "tobacco control", and to submit a concept for the evaluation. In particular, the German health monitoring system, and the evaluation and quality assurance of the Federal Center for Health Education provide a good data base for the evaluation of the health target. Lack of data exists regarding outcome and impact evaluation of structural (policy, legal) interventions. RECOMMENDATIONS: Evaluation of health targets requires continuing conduction of representative population surveys. The evaluation of national intervention campaigns and the extension of the topic "tobacco control" within the German health report system are necessary. The collection and documentation of information about intervention measures, programs, and evaluation results is recommended. The evaluation board favors follow-up studies, and the coordination of existing data resources; the creation of new evaluation systems is not required.
BACKGROUND: It has been argued that the inverse association between exposure to farm animals and nasal allergies observed in children and adults might be because of self-selection. AIMS: We aimed to assess the health-based selection out of farming in adults. MATERIAL AND METHODS: A cross-sectional study was carried out in a rural region. Overall, 4053 inhabitants (63%) aged 18-44 years responded to a questionnaire on respiratory diseases, life-time exposure to farming environments and potential confounders. For 2678 of these, specific immunoglobulin E to common allergens was available. The outcome was: (i) sensitization and symptoms of nasal allergies (symptomatic sensitization); (ii) sensitization without symptoms of nasal allergies (asymptomatic sensitization). RESULTS: Farm animal contact in childhood was associated with a decreased risk of symptomatic and asymptomatic sensitization. Continued exposure to farm animals in adulthood further decreased the odds ratio of symptomatic (odds ratio 0.2; 95% confidence interval 0.1, 0.4) but not asymptomatic sensitization (0.7; 0.4, 1.1). Starting farm animal contact in adulthood even increased the odds ratio of asymptomatic sensitization (2.4; 1.1, 5.2). CONCLUSIONS: The preventive effect of childhood contact to farm animals against sensitization continues into adulthood. However, in adulthood self-selection based on symptoms and underreporting of symptoms might also play a role.
PURPOSE: The purpose of this study was to compare the efficacy and toxicity of bendamustine, vincristine + prednisone (BOP) with a standard regimen of cyclophosphamide, vincristine + prednisone (COP) in patients with previously untreated advanced indolent non-Hodgkin's lymphoma (NHL) and mantle cell lymphoma. METHODS: A total of 164 patients with follicular lymphoma (grade 1/2), mantle cell lymphoma or lymphoplasmacytic lymphoma (immunocytoma) was randomised to treatment with vincristine 2 mg (day 1) and prednisone 100 mg/m2 (days 1-5) + bendamustine 60 mg/m2 (days 1-5) or + cyclophosphamide 400 mg/m2 (days 1-5) for a total of eight 21-day cycles. RESULTS: The rate of complete remission was 22% with BOP and 20% with COP. The projected 5-year survival rate was 61% with BOP and 46% with COP. The BOP-associated 5-year survival advantage almost reached significance in the subgroup of patients who responded to therapy (74% vs. 56%; P = 0.05), and did reach significance in responders who did not receive interferon maintenance therapy (70% vs. 47%; P = 0.03). Toxicity was acceptable in both treatment groups, although alopecia and leucopenia were more severe with COP. CONCLUSIONS: Bendamustine can efficaciously and safely replace cyclophosphamide, as used in standard COP therapy, for the treatment of patients with indolent NHL and mantle cell lymphoma. Long-term survival data suggest a clinically significant benefit for patients treated with BOP.
PURPOSE: The objective of this study was to investigate the effect of decision-to-delivery interval of crash emergency cesarean section on Apgar and umbilical artery pH in a level-3 university hospital. MATERIALS AND METHODS: In a retrospective analysis, all women undergoing "crash" emergency cesarean section were evaluated. Emergency cesarean sections were performed in the delivery room. Data relating to indication, Apgar score, arterial cord pH, and time intervals between decision-to-deliver and actual delivery were collected retrospectively. RESULTS: All 109 crash emergency cesarean sections were performed within a decision-to-delivery time of 30 min. The median (with 10-90th percentile) time was 10 min (5-19). Thirty-three (30.3%) of the emergency cesarean sections had a gestational age below 32 weeks and 60 (55%) below 37 weeks. An abnormal fetal heart rate pattern was noted in most of the cases (91%). Prolapsed cord (21%) and placental abruption (20%) were the most frequent reasons for emergency cesarean section but in one-fourth (25.7%) no morphological reason could be identified. Very short decision-to-delivery times below 20 min were inversely correlated to fetal outcome, i.e., lower umbilical blood pH and Apgar scores (P < 0.01). CONCLUSION: The 30-min standard for the decision-to-delivery time interval set by Anglo-American countries may be a feasible guideline at least for level-3 hospitals. The 20-min interval set by the German Society of Gynecology and Obstetrics could not be achieved in all cases. The positive effect of very short intervals on neonatal outcome still needs to be proven.
BACKGROUND: 100% oxygen is the commonly recommended gas for the resuscitation of infants at birth. There is growing evidence from both animal and human studies that room air is as effective as 100% oxygen and that 100% oxygen may have adverse effects on breathing physiology and cerebral circulation. There is also the theoretical risk of tissue damage due to free oxygen radicals when 100% oxygen is given. The use of room air has, therefore, been suggested as a safer and possibly more effective alternative. OBJECTIVES: In newborn infants requiring resuscitation, does the use of room air reduce the incidence of death, neurological disability and short term morbidity when compared with the use of 100% oxygen? SEARCH STRATEGY: This included searches of the Oxford Database of Perinatal Trials, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2004) and MEDLINE PubMed 1966 to December 2003, and handsearches of reference lists of relevant articles and conference proceedings. SELECTION CRITERIA: All randomised and quasi-randomised studies comparing the use of room air or any other concentration of oxygen versus 100% oxygen in the resuscitation of infants at birth. DATA COLLECTION AND ANALYSIS: Three authors assessed the methodological quality of eligible trials and extracted data independently. When appropriate, meta-analysis was conducted to provide a pooled estimate of effect. For categorical data the relative risk (RR), risk difference (RD) and number needed to treat (NNT) with 95% confidence intervals (CI) were calculated. Continuous data were analysed using weighted mean difference (WMD). MAIN RESULTS: Five studies were identified which enrolled a total of 1302 infants. In two studies allocation was randomised and the caregivers were blinded to intervention group. In the other three studies, allocation was quasi-randomised and the caregivers were not blinded. Pooled analysis of the four trials reporting effect on death showed a significant reduction in the rate of death in the group resuscitated with room air [typical RR 0.71 (0.54, 0.94), typical RD -0.05 (-0.08, -0.01), NNT 20 (12, 100)]. There were no significant differences between the groups with respect to rates of grade 2 or 3 hypoxic ischaemic encephalopathy. One of the four trials reported a statistically significant difference in median 5 minute Apgar scores, favouring the group allocated to room air. However, the absolute difference between the medians was small and there were no significant differences in the median 10 minute Apgar scores in the three trials reporting this outcome. One trial followed up a selected subgroup of survivors to 18-24 months. There were no significant differences in rates of adverse neurodevelopmental outcomes including cerebral palsy and failure to achieve various milestones; however, the proportion of eligible patients seen was less than 70%. Analyses that were planned for this review, but not able to be carried out because of lack of published data, included a sub-analysis stratified by gestational age and assessments of the effect on bronchopulmonary dysplasia and retinopathy of prematurity. AUTHORS' CONCLUSIONS: There is insufficient evidence at present on which to recommend a policy of using room air over 100% oxygen, or vice versa, for newborn resuscitation. A reduction in mortality has been seen in infants resuscitated with room air, and no evidence of harm has been demonstrated. However, the small number of identified studies and their methodologic limitations dictate caution in interpreting and applying these results. We note the use of back-up 100% oxygen in more than a quarter of infants randomised to room air. Therefore, on the basis of currently available evidence, if one chooses room air as the initial gas for resuscitation, supplementary oxygen should continue to be made available.
The implementation of health warnings leads to continuous dissemination of the latest scientific findings on the health consequences of smoking. In combination with other recognized effective tobacco control measures, a lower consumption and an increased quit-rate are thus to be stimulated. The effectiveness of health warnings depends on their content as well as on their design and size. Thus, large warnings are by far better than smaller warnings. The same applies for warnings that are placed on the front of cigarette packets. Warnings that incorporate pictures are considerably more effective than warnings based solely on text. The combination of pictures and text format is most effective. International experience shows that the dissemination of Quitline phone numbers in combination with health warnings on every packet clearly improves the effectiveness and broad reach of smoking cessation advice via Quitlines. The implementation of pictorial health warnings combined with the imprint of the phone number of the Quitline of the Federal Center for Heath Education is highly recommended in Germany.
S-Adenosylhomocysteine (AdoHcy) hydrolase deficiency has been proven in a human only once, in a recently described Croatian boy. Here we report the clinical course and biochemical abnormalities of the younger brother of this proband. This younger brother has the same two mutations in the gene encoding AdoHcy hydrolase, and has been monitored since birth. We report, as well, outcomes during therapy for both patients. The information obtained suggests that the disease starts in utero and is characterized primarily by neuromuscular symptomatology (hypotonia, sluggishness, psychomotor delay, absent tendon reflexes, delayed myelination). The laboratory abnormalities are markedly increased creatine kinase and elevated aminotransferases, as well as specific amino acid aberrations that pinpoint the aetiology. The latter include, most importantly, markedly elevated plasma AdoHcy. Plasma S-adenosylmethionine (AdoMet) is also elevated, as is methionine (although the hypermethioninaemia may be absent or nonsignificant in the first weeks of life). The disease seems to be at least to some extent treatable, as shown by improved myelination and psychomotor development during dietary methionine restriction and supplementation with creatine and phosphatidylcholine.
BACKGROUND: Guidelines gain importance for medical services. Their perception and use by physicians does not only rely on their attitudes towards guidelines, but also on other parameters of influence. PURPOSE: to assess hospital physicians's attitudes concerning clinical guidelines and physician- and hospital- related factors of influence. METHODS: multicenter survey with 99 junior and senior registrars from 30 departments of neurology (taking regional random samples). RESULTS: A majority of physicians regarded guidelines as a means of quality improvement and medical education. However, there were no generally positive or negative attitudes, but the physicians differentiated between the individual and the health system level. These patterns of attitudes did not depend upon aspects of the respective departments (such as size, internal guidelines, access to sources of information) and did not vary significantly between hospitals. Instead, there was a marked influence of personality traits on individual opinions concerning guideline utility. Senior registrars, less team-oriented physicians, younger physicians and the more prestige-motivated expressed positive attitudes. On the other hand, a sceptical and more negative attitude was found with professionals who expressed strong team orientation and scientific interest. CONCLUSIONS: The overall positive attitude is probably related to the identification of guideline users with their authors and also to the their present status as non-binding recommendations. The independence of attitudes from hospital characteristics, especially the existence of internal guidelines, may indicate either voluntary guideline use or rather a low impact of guidelines as management instruments or frequently used tools. The potential of guidelines for medical education does not seem to be fully utilised.
BACKGROUND: "Rauchfrei" -- the German part of the international contest "Quit and Win"-- is the biggest smoking cessation campaign in Germany. Already in the year 2000 24,925 smokers participated. A total of 90,458 adolescents and adults participated in "Rauchfrei 2002", that means about 0.5 % of all German smokers. OBJECTIVE: Main aim of the quit smoking campaign is to motivate as many smokers as possible to stop smoking for at least four-weeks and herewith to achieve a stop of the tobacco consumption in the long run. In this context the continuous 4-weeks and 12-months abstinence rates of the participants serve as indicators for success. METHODS: A survey with the adult participants aged 18 and older was carried out one year after each campaign. The samples were drawn randomly from all 10 German postal zip code-areas. A response rate of over 60 % in both surveys resulted in a sample size of n = 651 (2000) and n = 996 (2002). RESULTS: By the end of "Quit and Win 2000" (2002) 72 % (69 %) of the participants were smoke-free; 12 months after the campaign 30 % (22 %) of the participants were continuously smoke-free. Overall, men were more successful than women, and participants with a lower education were as successful as participants with a higher school education. Substantially more participants, who had received support from either family members, friends or colleagues, had abstinence rates above the average. CONCLUSION: "Rauchfrei" was successfully implemented in Germany and contributed to draw attention to the risks of smoking nationwide.
BACKGROUND: Up to now potential health effects of environmental exposure to intensive livestock production facilities have not been thoroughly studied. The aim of the Lower Saxony Lung Study (NiLS) was to assess the prevalence of respiratory symptoms and disease in an area with intensive animal production facilities taking into account environmental exposure to emissions from these large-scale farms. METHODS: All 10 864 inhabitants (age 18 to 44 years) of four towns with a large number of intensive animal production facilities in the area were invited to answer a mail-in questionnaire. Of these, 6416 subjects were randomly selected for the clinical part of the study (specific IgE, lung function measurements, bronchial provocation with methacholine). Overall, 6937 subjects answered the questionnaire (68 %), 60 % took part in the clinical tests. RESULTS: The prevalence of allergic disease in the study population was lower than in urban citizens. Subjects with more than 12 animal houses within 500 m of their home had an increased odds ratio for wheezing without a cold (odds ratio 2.7; 95 % confidence interval 1.4 - 5.4). They also showed a significantly decreased FEV (1) (mean 0.26 l; 0.04 l - 0.48 l) as well as a trend for a lower Tiffeneau-Index. CONCLUSIONS: In result, a large number of intensive animal production facilities might be associated with decreased lung function results in the immediate neighbours. Further studies are necessary to confirm our findings.
This study examines temporal differences in cigarette smoking initiation and cessation among male and female birth cohorts of 1926-1970 born in Germany. Based on the German Federal Health Survey 1998 the sample is divided into a series of 5-year sex-birth cohorts, beginning with those born between 1926 and 1930 and extending to those born between 1966 and 1970. The final data file consists of a sample of 5110 people. Ever-smoking prevalence among men varies from 60 to 70% between the birth cohorts, while in women born 1926-1930 ever-smoking increases from 20 to about 50% in those born 1966-1970. A reduction of the median age at starting smoking also takes place between the cohorts. With 8.5 years this decrease is more incisive among women, compared with a drop of 2 years among men. Regarding cessation patterns the analysis shows a shift towards a shorter duration of smoking with succeeding birth cohorts, again this shift is more incisive in women. But even in the youngest cohort still more than 50% of ever-smokers smoke regularly for more than 25 years. In Germany tobacco-control activities are required in order to take antismoking actions that especially prevent youth from starting to smoke and that support smokers in quitting.
AIM: To report survival and morbidity until discharge in preterm infants <501 g with life support started immediately after birth. METHODS/STUDY DESIGN: Cohort study of all preterm infants with birthweights < 501 g born in three tertiary perinatal centres between 1 January 1998 and 31 December 2001 (gestational age (GA) 25.2 [21.0-30.7] wk; birthweight 435 [290-500] g; median [range]). RESULTS: A total of 107 infants with birthweights <501 g were born. Twenty-nine were stillborn. A prenatal decision to initiate life support immediately after birth was reached in 9/37 (24%) infants <24.0 wk GA and in 39/42 (93%) infants > or =24.0 wk GA. Survival was 3/37 (8%) and 26/41 (63%) in infants <24 wk GA and > or =24.0 wk GA, respectively. Twenty-nine of the 48 infants with immediate life support (60%) survived (95% CI: 46-75%). Forty-two of these 48 (88%) infants were small for gestational age. No infant without immediate life support survived (0/30). Twenty-three (79%) survivors developed chronic lung disease (CLD) and eight (28%) received photocoagulation for retinopathy of prematurity (ROP). CONCLUSION: In this population of extremely low birthweight infants, survival was higher than in previous studies when life support was provided immediately after birth. Short-term morbidity was similar to other studies. The presented data on survival support our concept to offer immediate life support after birth in preterm infants with birthweights <501 g. The long-term outcome of these infants needs to be assessed urgently.