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PubMed1998

Systematic analysis and controlling of health care organisations lead to numerical health care improvements.

The EFQM model for organisational excellence is used in the health care sector as a tool to diagnose and assess the starting position for the effective QM programme. Feedback reports cover the fields of acute medical care, rehabilitation and ambulant care and contain strengths areas for improvement. Building on the EFQM feedback reports, the Modular Concept for Quality in Health Care ("Heidelberg Model") improves QM both holistically and specifically by implementing so-called "Modules for Excellence". The implementation process follows principles of project management covering medical, nursing and managing issues and the performance is periodically evaluated against targets. QM projects that are designed in the dichotomic way follow three goals. Organisational diagnosis and therapy lead to numerical health care improvements in "Prevention of nosocomial infections" and "Optimising out-patient treatment". Different assessment approaches lead to a diagnosing feedback report for QM in health care. The Modular Concept for Quality in Health Care ("Heidelberg Model") clusters, priorities, implements and evaluates the organisation's key areas for improvement.

Ambulatory Care↗
PubMed2005

Craniopharyngiomas in children and adults: systematic analysis of 121 cases with long-term follow-up.

BACKGROUND: Craniopharyngiomas account for 2-5% of all primary intracranial tumours. Despite their benign histological appearance, they are often associated with an unfavourable prognosis and their optimal treatment remains controversial. AIM: To analyse the natural history and treatment outcome of children and adults presenting to the Departments of Paediatrics and Endocrinology with craniopharyngioma between 1964 and 2003. PATIENTS AND METHODS: The records of 121 patients (age range 2.5-83 years, 42 aged < 16 and 79 aged > or = 16) were identified. The mean follow-up period since presentation was 103 months (8.6 years) (range 0.3-468 months). Sixteen patients underwent gross total removal (A), 3 gross total removal + radiotherapy (B), 51 partial removal (C), 33 partial removal + radiotherapy (D), 6 cyst evacuation alone (E) and 3 cyst evacuation + radiotherapy (F). The clinical, imaging and endocrinological data at presentation and during follow-up were analysed. RESULTS: Headache and visual field defects were the most common presenting clinical features (64% and 55%, respectively). Ninety-four per cent of the tumours had an extrasellar component and 23% of them were associated with hydrocephalus. There was a significant difference in the recurrence-free survival rates between groups A-D [at 10 years: 100% (A), 100% (B), 38% (C) and 77% (D), P < 0.01], which persisted even when analysing patients operated after 1980. The median time of first recurrence was 2.5 years (range 0.5-36). The peri-operative mortality of the patients who had any type of neurosurgical intervention due to recurrence was higher than that observed after primary surgery (24%vs. 1.8%) (P < 0.01). The rate of re-accumulation of the cyst fluid was 58% during the first year in patients of group E, whereas none of the subjects of group F experienced such an event during their follow-up period. There was no reversal of pre-existing pituitary hormone deficits after any surgical intervention. The probabilities of GH, FSH/LH, ACTH, TSH deficiency and diabetes insipidus at the 10-year follow-up were 88%, 90%, 86%, 80% and 65%, respectively. After excluding the non-tumour-related deaths, the 10-year survival rate following presentation was 90%. Patients with recurrence had a significantly lower probability for survival compared with those without it (at 10 years: 70%vs. 99%, P < 0.01). At the 10-year follow-up the probability of the presence of major visual field defects was 48%, hyperphagia/obesity 39%, epilepsy 12% and hemi-/monoparesis 11%. In this large series no substantial differences in the outcome of tumours diagnosed during childhood or adult life were found. CONCLUSIONS: Craniopharyngiomas remain tumours associated with significant morbidity. Gross total removal provides favourable results in terms of recurrences. If this cannot be achieved safely, adjuvant radiotherapy is beneficial in preventing tumour re-growth. Childhood- and adult-onset lesions generally behave similarly.

Adolescent↗
PubMed2005

Crohn's disease in mainland China: a systematic analysis of 50 years of research.

BACKGROUND: Crohn's disease appears to be increasing in frequency in many areas of the world. However, little information with regard to disease incidence, prevalence and temporal trends has been published in China. OBJECTIVE: The aim of this review is to better understand the occurrence of Crohn's disease in mainland China, and to give an overview of the current status of the disease. METHODS: We used a computer-based literature search using 50-years of records from the Chinese Database of Biology and Medicine (CBM, 1979-2002), combined with a manual year-by-year search of the literature from 1950 to 1979. Each article was double-reviewed, and all descriptive epidemiological data were recorded, pooled and statistically analyzed. RESULTS: In total, 1526 cases of Crohn's disease since 1950 have been reported by more than 50 hospitals from 22 provinces and cities in mainland China, comprising 884 male and 642 female patients, with a 1.38:1 male predominance. More than 70% of patients were aged 20 to 50 years old, with a mean age of 37.2 +/- 2.68 (ranging from 1 to 83) years. The extrapolated disease incidence and prevalence rates are 0.28/100,000 person years and 1.38/100,000 persons, respectively. CONCLUSIONS: The incidence and prevalence rates of Crohn's disease are still lower than those in Western and other Asian countries, but these rates have been increasing rapidly, and the disease is no longer uncommon. An underestimation may occur because the patients who were misdiagnosed or did not seek medical advice could not be included in the study. A future population-based survey is warranted.

Adolescent↗
PubMed2001

Systematic analysis of a conserved region of the aminoglycoside 6'-N-acetyltransferase type Ib.

Alanine-scanning mutagenesis was applied to the aminoglycoside 6'-N-acetyltransferase type Ib conserved motif B, and the effects of the substitutions were analyzed by measuring the MICs of kanamycin (KAN) and its semisynthetic derivative, amikacin (AMK). Several substitutions resulted in no major change in MICs. E167A and F171A resulted in derivatives that lost the ability to confer resistance to KAN and AMK. P155A, P157A, N159A, L160A, I163A, K168A, and G170A conferred intermediate levels of resistance. Y166A resulted in an enzyme derivative with a modified specificity; it conferred a high level of resistance to KAN but lost the ability to confer resistance to AMK. Although not as pronounced, the resistance profiles conferred by substitutions N159A and G170A were related to that conferred by Y166A. These phenotypes, taken together with previous results indicating that mutant F171L could not catalyze acetylation of AMK when the assays were carried out at 42 degrees C (D. Panaite and M. Tolmasky, Plasmid 39:123-133, 1998), suggest that some motif B amino acids play a direct or indirect role in acceptor substrate specificity. MICs of AMK and KAN for cells harboring the substitution C165A were high, suggesting that the active form of the enzyme may not be a dimer formed through a disulfide bond. Furthermore, this result indicated that the acetylation reaction occurs through a direct mechanism rather than a ping-pong mechanism that includes a transient transfer of the acetyl group to a cysteine residue. Deletion of fragments at the C terminus demonstrated that up to 10 amino acids could be deleted without a loss of activity.

Acetyltransferases↗
PubMed2006

Expression of IGF-I, IGF-II, and IGF-IR in gallbladder carcinoma. A systematic analysis including primary and corresponding metastatic tumours.

AIMS: The insulin-like growth factor (IGF) system has been implicated in tumour development and progression. This study was designed to analyse the expression of the IGF-I receptor (IGF-IR) and its ligands (IGF-I, IGF-II) in gallbladder cancer. METHODS: IGF-I, IGF-II, and IGF-IR immunoreactivity was investigated in 57 gallbladder carcinomas and corresponding lymph node (n = 11) and hepatic (n = 7) metastases using a tissue microarray technique and correlated with tumour stage, grade, and patient outcome. RESULTS: Cancer tissue allowing a reliable evaluation of IGF-I, IGF-II, and IGF-IR was present in 55 of 57 primary tumours and 17 of 18 metastases. IGF-I and IGF-II immunoreactivity was seen in 25 and 14 of the 55 primary tumours, in addition to six and three of the 17 metastases, respectively. No associations with tumour stage, grade, or prognosis were detected. IGF-IR was expressed in 52 of 55 primary tumours and all 17 metastases. IGF-IR staining intensity decreased with tumour cell dedifferentiation. Moreover, IGF-IR expression in less than 50% of cancer cells was an independent marker of poor prognosis in multivariate analysis (risk ratio, 4.0; 95% confidence interval, 1.4 to 11.2; p = 0.01). CONCLUSIONS: The expression of IGF-IR and its ligands provides evidence for the existence of an auto/paracrine loop of tumour cell stimulation in gallbladder cancer and makes this type of cancer a candidate for therapeutic strategies aimed at interfering with the IGF pathway. The recognition of IGF-IR as a new independent prognostic biomarker may help to identify patients who might benefit from adjuvant treatment.

Adenocarcinoma↗
PubMed1996

A systematic analysis of the mutations of the uroporphyrinogen III synthase gene in congenital erythropoietic porphyria.

Congenital erythropoietic porphyria (CEP) or Günther's disease is an inborn error of heme biosynthesis, transmitted as an autosomal recessive trait and characterized by a profound deficiency of uroporphyrinogen III synthase activity (UROIIIS). The molecular defects observed in CEP are mainly heterogeneous, except for one missense mutation, C73R (Cys to Arg substitution at codon 73) which represents nearly 40% of the disease alleles. A convenient strategy was designed to establish a rapid diagnosis at the genetic level in samples from patients with CEP. As a first step, the most frequent mutation is searched for by restriction analysis from genomic. DNA amplified by PCR. Next, the nine coding exons and intron-exon boundaries are sequenced from genomic DNA. As an alternative, the mutation can be determined by sequencing the UROIIIS cDNA of the patient, using the RT-PCR technique on RNAs when a lymphoblastoid cell line can be established. Finally, for each new mutation in UROIIIS coding sequence, the corresponding mutant protein is expressed in Escherichia coli, in order to demonstrate the pathological significance of the mutation. This work describes the analysis of UROIIIS gene mutations in 10 new families with CEP and summarizes the data from 20 unrelated families studied in our laboratory. Three new missense mutations of UROIIIS coding sequence (H173Y, Q187P and P248Q) have been observed together with 8 known mutations. The significance of three intronic base changes (476 -31 T-->C; 562 -4 A-->T; 562 -23 A-->G) is discussed. In 6 alleles out of 40 (15%), the mutation remains undetermined.

Adolescent↗
PubMed2001

Hypothesis: Beta-adrenergic receptor blockers and weight gain: A systematic analysis.

One of the arguments put forward against the primary use of beta-blockers has been concern about adverse metabolic effects, such as unfavorable effects on lipids or insulin sensitivity. Another less-appreciated potential drawback is their propensity to cause weight gain in some patients. In 8 evaluable prospective randomized controlled trials that lasted >/=6 months, body weight was higher in the beta-blocker than in the control group at the end of the study. The median difference in body weight was 1.2 kg (range -0.4 to 3.5 kg). A regression analysis suggested that beta-blockers were associated with an initial weight gain during the first few months. Thereafter, no further weight gain compared with controls was apparent. There was no relationship between demographic characteristics and changes in body weight. Based on these observations, the first-line use of beta-blockers in obese hypertensive patients should be reviewed. Obesity management in overweight hypertensive patients may be more difficult in the face of beta-blocker treatment.

Adrenergic beta-Antagonists↗
PubMed1979

Neurotic depressions: a systematic analysis of multiple criteria and meanings.

Neurotic depression, the most commonly used psychiatric diagnosis, has multiple meanings that are often used interchangeably in clinical practice. The authors identify six different meanings of neurotic depression and present data from a study of 90 depressed inpatients to determine how many patients met several different criteria; 16 patients met four sets of criteria. The overlap that exists between the different meanings is higher than chance alone but not sufficiently high to allow complete interchangeability. Until new diagnostic classes are developed, the authors recommend that the term "neurotic depression" no longer be used clinically because of its vagueness.

Adjustment Disorders↗
PubMed1998

Systematic analysis of snoring in women.

Nineteen percent of women are habitual snorers, yet most snoring studies report only on male snorers. The aim of this study was to identify the factors responsible for habitual snoring in women. Twenty-four snorers and 16 controls were studied prospectively in a special snoring clinic. Snorers were shorter (p = .005) and heavier (p = .001), and with greater body mass index (BMI: p < .001), collar size (p = .002), and submental skinfold thickness (p = .001) than controls. The area of the posterior pharyngeal wall visible on oral examination was smaller in snorers (p = .005). Acoustic rhinometry areas and volumes were similar in the two groups. Nasal flow-volume loops showed reduced expiratory (p = .01) and inspiratory (p = .07) flow in snorers. Inspiratory flow correlated inversely with nasal symptoms (p < .05). The factors that best predict habitual snoring in women are a high BMI, a high nasal symptom score, and heavy weight. Of these, BMI is the most powerful.

Adolescent↗
PubMed2002

Identifying functional relationships among human genes by systematic analysis of biological literature.

BACKGROUND: The availability of biomedical literature in electronic format has made it possible to implement automatic text processing methods to expose implicit relationships among different documents, and more importantly, the functional relationships among the molecules and processes that these documents describe. RESULTS: A computational strategy that identifies functionally related human genes by detecting the implicit relationships among the publications cited under each gene in the Online Mendelian Inheritance in Man (OMIM) was implemented. The implementation was based on a substantially modified version of the kernel document method. The improvements include assigning a calculated weight for a document to indicate its importance in establishing the relationship between two documents, and using multiple kernel documents to reflect the multiple functions of the same gene. An example of using this strategy to identify genes related to the apoptosis pathway in human was given. CONCLUSIONS: The results showed that this method can indeed produce meaningful results when applied to human genes.

Apoptosis↗
PubMed2005

Systematic analysis of gene expression in human brains before and after death.

BACKGROUND: Numerous studies have employed microarray techniques to study changes in gene expression in connection with human disease, aging and evolution. The vast majority of human samples available for research are obtained from deceased individuals. This raises questions about how well gene expression patterns in such samples reflect those of living individuals. RESULTS: Here, we compare gene expression patterns in two human brain regions in postmortem samples and in material collected during surgical intervention. We find that death induces significant expression changes in more than 10% of all expressed genes. These changes are non-randomly distributed with respect to their function. Moreover, we observe similar expression changes due to death in two distinct brain regions. Consequently, the pattern of gene expression differences between the two brain regions is largely unaffected by death, although the magnitude of differences is reduced by 50% in postmortem samples. Furthermore, death-induced changes do not contribute significantly to gene expression variation among postmortem human brain samples. CONCLUSION: We conclude that postmortem human brain samples are suitable for investigating gene expression patterns in humans, but that caution is warranted in interpreting results for individual genes.

Adolescent↗
PubMed2006

Systematic analysis of myotubularins: heteromeric interactions, subcellular localisation and endosome related functions.

The myotubularins are a large family of lipid phosphatases with specificity towards PtdIns3P and PtdIns(3,5)P(2). Each of the 14 family members bears a signature phosphatase domain, which is inactive in six cases due to amino acid changes at the catalytic site. Fragmentary data have indicated heteromeric interactions between myotubularins, which have hitherto paired an active family member with an inactive one. In this study we have conducted a largescale analysis of potential associations within the human myotubularin family, through directed two-hybrid screening and immunoprecipitation of epitope-tagged proteins. We have confirmed all previously reported combinations and identified novel heteromeric interactions: MTMR8 with MTMR9, and MTMR3 with MTMR4, the first such combination of enzymatically active MTMs. We also report the capacity of several family members to self-associate, including MTMR3 and MTMR4. Subcellular localisation studies reveal a unique distribution of MTMR4 to endosomal structures, the major site of substrate lipid accumulation. All active MTMs we have tested (MTM1, MTMR2-MTMR4) reduce endosomal PtdIns3P levels upon overexpression. Despite this, only MTMR4 exerts any effect on EGF receptor trafficking and degradation, which is more pronounced with a phosphatase inactive form of MTMR4 and requires an intact FYVE domain.

Endosomes↗
PubMed2004

Systematic analysis of SNARE molecules in Arabidopsis: dissection of the post-Golgi network in plant cells.

In all eucaryotic cells, specific vesicle fusion during vesicular transport is mediated by membrane-associated proteins called SNAREs (soluble N-ethyl-maleimide sensitive factor attachment protein receptors). Sequence analysis identified a total of 54 SNARE genes (18 Qa-SNAREs/Syntaxins, 11 Qb-SNAREs, 8 Qc-SNAREs, 14 R-SNAREs/VAMPs and 3 SNAP-25) in the Arabidopsis genome. Almost all of them were ubiquitously expressed through out all tissues examined. A series of transient expression assays using green fluorescent protein (GFP) fused proteins revealed that most of the SNARE proteins were located on specific intracellular compartments: 6 in the endoplasmic reticulum, 9 in the Golgi apparatus, 4 in the trans-Golgi network (TGN), 2 in endosomes, 17 on the plasma membrane, 7 in both the prevacuolar compartment (PVC) and vacuoles, 2 in TGN/PVC/vacuoles, and 1 in TGN/PVC/plasma membrane. Some SNARE proteins showed multiple localization patterns in two or more different organelles, suggesting that these SNAREs shuttle between the organelles. Furthermore, the SYP41/SYP61-residing compartment, which was defined as the TGN, was not always located along with the Golgi apparatus, suggesting that this compartment is an independent organelle distinct from the Golgi apparatus. We propose possible combinations of SNARE proteins on all subcellular compartments, and suggest the complexity of the post-Golgi membrane traffic in higher plant cells.

Amino Acid Sequence↗