MHC-B variability within the Finnish Landrace chicken conservation program.

The major histocompatibility complex (MHC) is a cluster of genes involved with immune responses. The chicken MHC has been shown to influence resistance to viruses, bacteria, and infections from both internal and external parasites. The highly variable chicken MHC haplotypes were initially identified by the use of haplotype-specific serological reagents. A novel SNP-based panel encompassing 210,000 bp of the MHC-B locus was developed to allow fine scale genetic analyses including rapid identification of novel haplotypes for which serological reagents are not available. The Finnish Landrace breed of chickens traces its origins to almost 1,000 years ago, with multiple lineages maintained as small populations in isolated villages. The breed is well adapted to the cooler Finnish climate and is considered to be an infrequent egg layer. Conservation efforts to protect this endangered breed were initiated by a hobby breeder in the 1960s. An official conservation program was established in 1998 and now 12 different populations are currently maintained by a network of volunteer hobbyist breeders. Variation in the MHC-B region in these populations was examined using a panel of 90 selected SNP. A total of 195 samples from 12 distinct populations (average of 15 individuals sampled per population) were genotyped with the 90 SNP panel specific for the MHC-B region, spanning 210,000 bp. There were 36 haplotypes found, 16 of which are a subset of 78 that had been previously identified in either commercially utilized or heritage breeds from North America with the remaining 20 haplotypes being novel. The average number of MHC-B haplotypes found within each Finnish Landrace population was 5.9, and ranged from one to 13. While haplotypes common to multiple populations were found, population-specific haplotypes were also identified. This study shows that substantial MHC-B region diversity exists in the Finnish Landrace breed and exemplifies the significance tied to conserving multiple populations of rare breeds.

Survival and tissue maintenance of an implant with a sloped configurated shoulder in the posterior mandible-a prospective multicenter study.

AIM: Clinical studies evaluating the influence of the implant design on the preservation of peri-implant keratinized mucosa are rare. The aim of this prospective multicenter study was to investigate the survival, and soft and hard tissue maintenance of an implant with a sloped shoulder configuration, when placed in the posterior mandible. MATERIAL AND METHODS: In this study, 24 centers participated and 184 patients receiving 238 implants (OsseoSpeed™ Profile TX implants) were included. Clinical assessments of soft tissue parameters were performed before implant placement, immediately after implant placement, at prosthetic delivery and at 6, 12 and 24 months after implant placement and marginal bone adaptation was examined. RESULTS: After an average time in situ of 28.7 ± 4.7 months (2.4 ± 0.4 years), the survival rate was 99.2%. Analysis of the peri-implant soft tissues during follow-up showed a slight but significant increase in peri-implant keratinized mucosa width after 2 years (P < 0.001). All patients with reduced peri-implant keratinized mucosa width of ≤ 2 mm at postoperative examination (n = 95) showed a pronounced and statistically significant increase in the peri-implant keratinized mucosa width over time (P < 0.001). After a mean follow-up of 20.7 ± 8 months (1.7 ± 0.7 years), mean inter-proximal marginal bone loss was 0.30 ± 0.6 mm, indicating high bone stability around the sloped implant neck. CONCLUSION: These results indicate that sloped configurated implants have a high survival rate after 2 years in function. The sloped implant shoulder configuration helps to support the hard and soft tissue around the implant neck and supports the regain of a physiological peri-implant keratinized mucosa in patients with compromised peri-implant soft tissue conditions (Clinicaltrials.gov: NCT01400321).

MHC variability in heritage breeds of chickens.

The chicken Major Histocompatibility Complex (MHC) is very strongly associated with disease resistance and thus is a very important region of the chicken genome. Historically, MHC (B locus) has been identified by the use of serology with haplotype specific alloantisera. These antisera can be difficult to produce and frequently cross-react with multiple haplotypes and hence their application is generally limited to inbred and MHC-defined lines. As a consequence, very little information about MHC variability in heritage chicken breeds is available. DNA-based methods are now available for examining MHC variability in these previously uncharacterized populations. A high density SNP panel consisting of 101 SNP that span a 230,000 bp region of the chicken MHC was used to examine MHC variability in 17 heritage populations of chickens from five universities from Canada and the United States. The breeds included 6 heritage broiler lines, 3 Barred Plymouth Rock, 2 New Hampshire and one each of Rhode Island Red, Light Sussex, White Leghorn, Dark Brown Leghorn, and 2 synthetic lines. These heritage breeds contained from one to 11 haplotypes per line. A total of 52 unique MHC haplotypes were found with only 10 of them identical to serologically defined haplotypes. Furthermore, nine MHC recombinants with their respective parental haplotypes were identified. This survey confirms the value of these non-commercially utilized lines in maintaining genetic diversity. The identification of multiple MHC haplotypes and novel MHC recombinants indicates that diversity is being generated and maintained within these heritage populations.

Cerebral oxygen saturation and cardiac output during anaesthesia in sitting position for neurosurgical procedures: a prospective observational study.

BACKGROUND: Neurosurgical operations in the dorsal cranium often require the patient to be positioned in a sitting position. This can be associated with decreased cardiac output and cerebral hypoperfusion, and possibly, inadequate cerebral oxygenation. In the present study, cerebral oxygen saturation was measured during neurosurgery in the sitting position and correlated with cardiac output. METHODS: Perioperative cerebral oxygen saturation was measured continuously with two different monitors, INVOS® and FORE-SIGHT®. Cardiac output was measured at eight predefined time points using transoesophageal echocardiography. RESULTS: Forty patients were enrolled, but only 35 (20 female) were eventually operated on in the sitting position. At the first time point, the regional cerebral oxygen saturation measured with INVOS® was 70 (sd 9)%; thereafter, it increased by 0.0187% min-1 (P<0.01). The cerebral tissue oxygen saturation measured with FORE-SIGHT® started at 68 (sd 13)% and increased by 0.0142% min-1 (P<0.01). The mean arterial blood pressure did not change. Cardiac output was between 6.3 (sd 1.3) and 7.2 (1.8) litre min-1 at the predefined time points. Cardiac output, but not mean arterial blood pressure, showed a positive and significant correlation with cerebral oxygen saturation. CONCLUSIONS: During neurosurgery in the sitting position, the cerebral oxygen saturation slowly increases and, therefore, this position seems to be safe with regard to cerebral oxygen saturation. Cerebral oxygen saturation is stable because of constant CO and MAP, while the influence of CO on cerebral oxygen saturation seems to be more relevant. CLINICAL TRIAL REGISTRATION: NCT01275898.

Genetic Analysis of Termite Colonies in Wisconsin.

The objective of this study was to document current areas of subterranean termite activity in Wisconsin and to evaluate genetic characteristics of these northern, peripheral colonies. Here, amplified fragment-length polymorphism was used to characterize levels of inbreeding, expected heterozygosity, and percent polymorphism within colonies as well as genetic structure among populations sampled. Genetic analysis revealed two species of termites occur in Wisconsin, Reticulitermes flavipes (Kollar) and Reticulitermes tibialis Banks, both found in the southern half of the state. Colonies of both species in Wisconsin are thought to represent the northern boundary of their current distributions. Measurements of within colony genetic variation showed the proportion of polymorphic loci to be between 52.9-63.9% and expected heterozygosity to range from 0.122-0.189. Consistent with geographical isolation, strong intercolony genetic differences were observed, with over 50% of FST values above 0.25 and the remaining showing moderate levels of genetic differentiation. Combined with low levels of inbreeding in most collection locations (FIS 0.042-0.123), we hypothesize termites were introduced numerous times in the state, likely by anthropogenic means. We discuss the potential effects of these genetic characteristics on successful colony establishment of termites along the northern boundary compared with termites in the core region of their distribution.

A Novel Study Paradigm for Long-term Prevention Trials in Alzheimer Disease: The Placebo Group Simulation Approach (PGSA): Application to MCI data from the NACC database.

INTRODUCTION: The PGSA (Placebo Group Simulation Approach) aims at avoiding problems of sample representativeness and ethical issues typical of placebo-controlled secondary prevention trials with MCI patients. The PGSA uses mathematical modeling to forecast the distribution of quantified outcomes of MCI patient groups based on their own baseline data established at the outset of clinical trials. These forecasted distributions are then compared with the distribution of actual outcomes observed on candidate treatments, thus substituting for a concomitant placebo group. Here we investigate whether a PGSA algorithm that was developed from the MCI population of ADNI 1*, can reliably simulate the distribution of composite neuropsychological outcomes from a larger, independently selected MCI subject sample. METHODS: Data available from the National Alzheimer's Coordinating Center (NACC) were used. We included 1523 patients with single or multiple domain amnestic mild cognitive impairment (aMCI) and at least two follow-ups after baseline. In order to strengthen the analysis and to verify whether there was a drift over time in the neuropsychological outcomes, the NACC subject sample was split into 3 subsamples of similar size. The previously described PGSA algorithm for the trajectory of a composite neuropsychological test battery (NTB) score was adapted to the test battery used in NACC. Nine demographic, clinical, biological and neuropsychological candidate predictors were included in a mixed model; this model and its error terms were used to simulate trajectories of the adapted NTB. RESULTS: The distributions of empirically observed and simulated data after 1, 2 and 3 years were very similar, with some over-estimation of decline in all 3 subgroups. The by far most important predictor of the NTB trajectories is the baseline NTB score. Other significant predictors are the MMSE baseline score and the interactions of time with ApoE4 and FAQ (functional abilities). These are essentially the same predictors as determined for the original NTB score. CONCLUSION: An algorithm comprising a small number of baseline variables, notably cognitive performance at baseline, forecasts the group trajectory of cognitive decline in subsequent years with high accuracy. The current analysis of 3 independent subgroups of aMCI patients from the NACC database supports the validity of the PGSA longitudinal algorithm for a NTB. Use of the PGSA in long-term secondary AD prevention trials deserves consideration.

The prognostic value of lymph node ratio and updated TNM classification in rectal cancer patients with adequate versus inadequate lymph node dissection.

BACKGROUND: The aim of this study was to clarify whether the lymph node ratio (LNR) is superior to the updated TNM classification regarding the prognosis of stage III rectal cancer patients who have not undergone neoadjuvant therapy. The TNM system is based on the absolute number of lymph nodes involved, and the LNR takes into account involved and examined nodes. METHODS: In 237 patients with stage III rectal cancer, we evaluated prognostic factors for 5-year overall survival (OS), disease-free survival (DFS), and risk of distant metastases (DM) using the Kaplan-Meier method, with patients divided based on adequate versus inadequate lymph node dissection (≥12 vs. <12 lymph nodes examined). The updated TNM divides patients into four groups (1, 2-3, 4-6, and ≥7 involved nodes), while LNR divides patients into quartiles. Multivariate Cox regression analyses were performed. RESULTS: Among patients with adequate lymph node dissection, the distributions within the two systems were in agreement in 141/178 (79.2 %, kappa 0.721), and the predictive values for OS, DFS, and DM were similar. In patients with inadequate lymph node dissection, the classifications of both systems were concordant in only 13/59 (22 %, kappa 0.021). The pN system significantly under-staged patients, while the LNR classification was a better predictor of OS, DFS, and DM. CONCLUSIONS: In patients with adequate lymph node dissection, LNR staging does not add substantial information to the predictions of updated TNM lymph node staging. However, in patients with inadequate lymph node harvesting, the LNR compensates for the under-staging of the TNM classification and provides a better estimation of prognosis than the updated TNM system.

Time course of cerebrovascular autoregulation during extreme Trendelenburg position for robotic-assisted prostatic surgery.

Trendelenburg positioning in combination with pneumoperitoneum during robotic-assisted prostatic surgery possibly impairs cerebrovascular autoregulation. If cerebrovascular autoregulation is disturbed, arterial hypertension might induce cerebral hyperaemia and brain oedema, while low arterial blood pressure can induce cerebral ischaemia. The time course of cerebrovascular autoregulation was investigated during use of the Trendelenburg position and a pneumoperitoneum for robotic-assisted prostatic surgery using transcranial Doppler ultrasound. Cerebral blood flow velocity was correlated with arterial blood pressure and the autoregulation index (Mx) was calculated. In 23 male patients, Mx was assessed at baseline, after induction of general anaesthesia, during the Trendelenburg position (40-45°), and after repositioning. During the Trendelenburg position, Mx increased over time, indicating an impairment of cerebrovascular autoregulation. After repositioning, Mx recovered to baseline levels. It can be concluded that with longer durations of Trendelenburg position and pneumoperitoneum, cerebrovascular autoregulation deteriorates, and, therefore, blood pressure management should be adapted to avoid cerebral oedema and the duration of Trendelenburg position should be as short as possible.

Associations between single-nucleotide polymorphisms of the VEGF gene and long-term prognosis of oral squamous cell carcinoma.

INTRODUCTION: Functional polymorphisms (SNPs) of the vascular endothelial growth factor (VEGF) are associated with the incidence of oral squamous cell carcinoma (OSCC). An impact of VEGF-SNPs on prognosis of OSCC patients seems possible. Therefore, correlations between prognostic parameters of OSCC patients and five VEGF-SNPs were determined. MATERIALS AND METHODS: In a retrospective long-term study, in 113 OSCC patients that underwent curative resections, five VEGF-SNPs (-1154 G/A, +405 G/C, +936 C/T, -2578 C/A, and -460 C/T) were analyzed. Associations between SNPs and prognosis (incidence of local recurrent disease, second cancer, metastases, death, total disease-free survival) were examined. RESULTS: After a mean follow-up time of 57.6 months, 32 patients had local recurrences; 15 patients had second cancer, 15 patients metastases, and 23 patients died. The mean disease-free survival was 43.1 months. A significant increased incidence of OSCC in smokers with the VEGF -2578 A/C and -460 C/T SNP was seen (each P < 0.0001). In univariate analysis, patients with advanced OSCCs (T > 2 or N > 0) together with the -1154 A/A allele had a significant worse survival and a worse disease-free survival (both P < 0.04). The same was seen for the +405 G/G SNP (both P = 0.002). In multivariate analysis, only the negative influence of the +405 G/G SNP on survival in advanced OSCCs (T > 2) could be confirmed (P = 0.002). DISCUSSION: Possible reciprocal interactions between smoking and VEGF-SNP function were observed. Multivariate analysis confirmed the VEGF +405 G/G genotype to be associated with poor survival in advanced OSCCs; a further use of this haplotype as biomarker has to be discussed.

GDF 15 as an anti-apoptotic, diagnostic and prognostic marker in oral squamous cell carcinoma.

Growth-differentiation factor 15 (GDF 15) is involved in tumor pathogenesis and its expression is increased in many types of cancers. Functional effects of GDF 15 on oncogenesis of oral squamous cell carcinoma (OSCC) remain unclear. Therefore, the aim of this study was to examine the apoptotic characteristics of GDF 15 in OSCC cell lines in vitro and to analyze serum GDF 15 concentrations as a diagnostic and prognostic tumor marker for OSCC in vivo. Caspase activity was assessed in OSCC cell lines with the Caspase-Glo 3/7 system. Serum GDF 15 concentrations from 64 patients with histopathological proven OSCC and from 30 healthy volunteers were measured using an enzyme-linked immunosorbent assay. In 21 patients, serum GDF 15 was also analyzed postoperatively. In vitro, treatment of OSCC cell lines with GDF 15 reduced Caspase 3/7 activity significantly (p<0.05). In vivo, serum GDF 15 concentrations of the OSCC patients in all stages of OSCC were significantly higher than those of the healthy subjects (p<0.0001). After surgery, GDF 15 concentrations declined significantly from 1545±774pg/ml preoperative to 953±438pg/ml postoperative (p=0.003). The median survival time of OSCC patients with GDF 15 levels below 875pg/ml was significantly higher than of OSCC patients with GDF 15 levels above or equal 875pg/ml (p=0.031). Determination of receiver operating characteristic curves (ROC) showed a respective area under the ROC curve (AUC) of 0.943. The anti-apoptotic effect of GDF 15 in OSCC cell lines was shown in vitro. In vivo, significant elevated serum GDF 15 levels with prognostic value in OSCC-patients were seen for the first time. The results indicate that GDF15 may be used as a potential marker for diagnosis and prognosis of this entity.

Neuropsychological dysfunction, depression, physical disability, and coping processes in families with a parent affected by multiple sclerosis.

BACKGROUND: Families with a parent suffering from multiple sclerosis (MS) must cope with the unpredictable course of the disease. Most studies analyzing factors that influence coping abilities in families with a member affected with MS used questionnaires to assess this ability. METHODS: On the contrary, the present study used a semi-structured psychiatric interview and used the resulting information to calculate a general measure of coping ability (coping index [CI]). We administered this interview to 44 MS patients, their partners and offspring and conducted a neuropsychological and physical evaluation of the patients to determine the impact of physical disability, cognitive dysfunction, and depression on the process of coping by the patient, the healthy partner, and children. RESULTS: The CI of patients was best predicted by measures of their depressive symptoms, divided attention, and estimated verbal intelligence. None of the patient variables predicted the CI of healthy partners or their offspring. We found an association between the CI of the healthy partner and the children. CONCLUSIONS: These findings suggest that MS patients' emotional and neuropsychological functions are associated with their ability to cope with the disease. These should be carefully assessed at the beginning of treatment so that those factors known to negatively influence patient coping are targeted in the treatment plan if necessary. Comprehensive care of a patient with MS should include support of coping abilities of the family members.

Evaluation of diagnostic scores with adjustment for covariates.

Diagnostic tests yield measurements on very different types of scales. Quantitative scales may consist of non-negative integers, either unbounded or bounded, with a fixed number of different values, or they may consist of continuous or percentage values. Remembering a different threshold value for each diagnostic variable would be cumbersome, in particular if covariates have to be taken into account. As a convenient way to overcome such problems we propose to compute z-scores for all measurements. They will be adjusted for covariates so that any individual can be judged on any test result on one single scale with an appropriate standard normal quantile as threshold. Two issues need to be addressed: Selection of covariates in the regression model which delivers the adjustment and normality of the residuals. The first will be treated by cross-validation and the latter by applying an appropriate transformation. We apply this methodology to neuropsychological tests and adjust for age, length of education and sex. Normality of residuals is needed on the diagnostically relevant side only. This allows to use parametric transformations, which can be easily implemented, e.g. in database systems. Since we have measurements at baseline and at follow-up we also analyze change values in a similar manner. For ease of interpretation, we transform the resulting z-scores back to the original scale.

Prospective evaluation of the macroscopic types and location of early Barrett's neoplasia in 380 lesions.

BACKGROUND AND STUDY AIMS: The macroscopic appearance of early gastric cancers, classified according to the Japanese criteria, has been shown to be an important prognostic factor for local endoscopic therapy. No prospective data about the distribution of macroscopic types and their location in early Barrett's neoplasia are available, however. The present study was conducted to evaluate the clinical applicability of this macroscopic classification and to analyze the relative proportions of the different gross types in early Barrett's neoplasms and the correlation between the macroscopic classification and the stage or grade of differentiation. PATIENTS AND METHODS: A total of 344 patients with 380 Barrett's neoplastic lesions who were referred between October 1996 and September 2005 for endoscopic therapy of early Barrett's high-grade intraepithelial neoplasia and carcinoma were prospectively included in the study. Routine endoscopy prior to endoscopic resection in our center included assessment of the macroscopic type (according to the Japanese classification) and documentation of the radial location of the neoplastic lesions. Images were recorded which were later assessed by six independent reviewers; intra- and interobserver agreement for the assessment of the macroscopic type were calculated using kappa statistics. RESULTS: The distribution of the lesions by gross type was as follows: type I, n = 49 (13 %); type IIa, n = 139 (37 %); type IIb, n = 106 (28 %); type IIc, n = 17 (4 %); type IIa + c, n = 62 (16 %); type III, n = 7 (2 %). Type IIb lesions seem to be the most favorable type with regard to differentiation and T category ( P < 0.05). The mean kappa value for the interobserver agreement was 0.86 and the mean kappa value for the intraobserver agreement was 0.89. Most lesions were found at the 12 o'clock and 3 o'clock positions. CONCLUSIONS: Assessment of the macroscopic type may provide important information about the possibility of endoscopic treatment. The harder-to-detect flat lesions are by far the most frequent macroscopic type of neoplastic lesion in Barrett's esophagus.

Curative endoscopic therapy in patients with early esophageal squamous-cell carcinoma or high-grade intraepithelial neoplasia.

BACKGROUND AND STUDY AIMS: Endoscopic resection of esophageal squamous-cell neoplasia with curative intent is considered to be a safe and effective alternative treatment to radical surgery in cases where the neoplasia is intraepithelial or limited to the mucosal layer. These patients are at risk for recurrent malignancy in the preserved esophagus, however. We conducted a prospective study to evaluate the efficacy and safety of endoscopic resection and to analyze variables associated with recurrence in patients with mucosal or intraepithelial squamous-cell neoplasia. PATIENTS AND METHODS: Between December 1997 and September 2005, 65 patients (mean age +/- standard deviation [SD] 62.9 +/- 9.5 years), 12 with high-grade intraepithelial neoplasia (HGIN) and 53 with mucosal squamous-cell cancer, were included in our study and were treated using endoscopic resection. Details of patient and tumor characteristics were documented prospectively. All patients were included in a staging protocol including high-resolution endoscopy with Lugol staining, endoscopic ultrasound, computed tomography, and abdominal ultrasound. Endoscopic resection was performed using a ligation technique. The data acquired were subjected to univariate and multivariate analysis. RESULTS: A total of 179 resections were performed (mean number of resections +/- SD per patient, 2.8 +/- 1.8): 11/12 patients with HGIN (91.7%), and 51/53 patients with mucosal cancer (96.2%) achieved a complete response during a mean follow-up period of 39.3 +/- 22.8 months; three patients were still under therapy at the end of the study period. Recurrence of malignancy after achieving a complete response was observed in 16 patients (26%), but these patients all achieved another complete response after further endoscopic treatment. Independent risk factors for recurrence was multifocal carcinoma (RR 4.1, P = 0.018). Tumor-related deaths occurred in two patients (3%), and eight patients died as a result of co-morbidity. Complications were seen in 15/65 patients (23%, all esophageal stenoses). The 7 year survival rate calculated for all groups was 77%. CONCLUSIONS: According to the results of long-term follow-up in this study, endosocopic resection appears to be an effective and safe method of curative treatment in patients with HGIN and mucosal squamous-cell carcinomas of the esophagus. Multifocal carcinoma and T1m1 tumors seem to be highly associated with recurrence.

Normal ranges of neuropsychological tests for the diagnosis of Alzheimer's disease.

The diagnosis of early stage dementia is a highly complex process involving not only a somatic examination but also a neuropsychological assessment of the patient's cognitive capability. The American 'Consortium to Establish a Registry for Alzheimer's Disease' (CERAD) has proposed a set of tests in English which has been translated into German. This paper presents the statistical methodology applied to determine normal ranges adjusted for demographic variables for the German CERAD neuropsychological assessment battery (CERAD-NAB). The study population consists of participants of the Basel Study on the Elderly (Project BASEL) which aims at identifying preclinical markers of Alzheimer's disease. The normative sample has been defined by carefully excluding potentially relevant medical history and concomitant diseases and consists of 617 participants which are between 53 and 92 years old. Test results should be adjusted for gender, age, and years of education. For this purpose, a set of linear models including these predictors and subsets of their interactions and squares was evaluated for all 11 test scores derived from the CERAD-NAB battery. Model selection was based on the PRESS (predicted residual sum of squares) statistic. Although a strict application of this criterion selected 6 different models, a slight compromise allowed to fit all test scores by two models. In several tests of the CERAD-NAB many participants achieve maximal scores. Residuals of such test scores are heavily skewed. An arcsine transformation has been tuned to the data, so that residuals are close to a normal distribution, at least for residuals in the lower quartile which is relevant in diagnosing cognitive impairment. Test results are finally presented as z-scores which can be easily compared to a standard normal distribution. The evaluation of the CERAD-NAB is implemented on the Internet and in an Excel application.

Evolution of the RECQ family of helicases: A drosophila homolog, Dmblm, is similar to the human bloom syndrome gene.

Several eukaryotic homologs of the Escherichia coli RecQ DNA helicase have been found. These include the human BLM gene, whose mutation results in Bloom syndrome, and the human WRN gene, whose mutation leads to Werner syndrome resembling premature aging. We cloned a Drosophila melanogaster homolog of the RECQ helicase family, Dmblm (Drosophila melanogaster Bloom), which encodes a putative 1487-amino-acid protein. Phylogenetic and dot plot analyses for the RECQ family, including 10 eukaryotic and 3 prokaryotic genes, indicate Dmblm is most closely related to the Homo sapiens BLM gene, suggesting functional similarity. Also, we found that Dmblm cDNA partially rescued the sensitivity to methyl methanesulfonate of Saccharomyces cerevisiae sgs1 mutant, demonstrating the presence of a functional similarity between Dmblm and SGS1. Our analyses identify four possible subfamilies in the RECQ family: (1) the BLM subgroup (H. sapiens Bloom, D. melanogaster Dmblm, and Caenorhabditis elegans T04A11.6); (2) the yeast RECQ subgroup (S. cerevisiae SGS1 and Schizosaccharomyces pombe rqh1/rad12); (3) the RECQL/Q1 subgroup (H. sapiens RECQL/Q1 and C. elegans K02F3.1); and (4) the WRN subgroup (H. sapiens Werner and C. elegans F18C5.2). This result may indicate that metazoans hold at least three RECQ genes, each of which may have a different function, and that multiple RECQ genes diverged with the generation of multicellular organisms. We propose that invertebrates such as nematodes and insects are useful as model systems of human genetic diseases.

Improving the diagnostic accuracy of the Mini-Mental State Examination.

INTRODUCTION: We determined the diagnostic accuracy of the Mini-Mental State Examination (MMSE) for dementia of the Alzheimer type (DAT) in an outpatient geriatric referral center in Switzerland. MATERIAL & METHODS: DAT patients and elderly controls were assigned to two groups: a validation sample (70 DAT patients; 50 controls) and a cross-validation sample (133 DAT patients; 43 controls). A Receiver Operating Characteristic curve was generated to derive the optimal MMSE cut-off score in the validation sample. RESULTS: The optimal MMSE cut-off was < 26/30 (sensitivity of 74%, specificity of 100%). Adjustments for age and education were necessary. The cross-validation confirmed these findings. CONCLUSION: iN A clinical setting the MMSE cut-off should be increased to < 26/30. A thorough neurobehavioral assessment is still necessary for a complete evaluation.

[An effective method for the estimation and comparison of the ED50 with small sample sizes]. / Eine effektive Methode zur Schätzung und zum Vergleich der ED50 bei kleinen Fallzahlen.

In ED50 experiments the relationship between dose and probability of response is often modelled by the probit function. Standard statistical analysis estimates the parameters of this function by the maximum likelihood principle and derives the ED50 and its fiducial limits from these parameters. Bayesian analysis is more effective in two respects: It optionally includes prior information and in all but very few instances yields confidence intervals, whereas fiducial intervals often cannot be determined. Bayesian analysis of experiments with one substance has been treated in GRIEVE (1988). In the present article the mathematically interested reader is shown how to compare two substances. The probability of higher ED50 in the one substance as well as estimates of the ratio of the ED50's are obtained. The methods are easily extended to the effective dose for any other reasonable percentage of animals, e.g. ED90 or ED25. Experiments concerning lethal doses can be analysed by these methods as well. Both types of analysis are applied in two examples which compare new batches of vaccines with an established standard. In the first example both substances are nearly equivalent, while in the second example the new batch is considerably more efficient. An interactive FORTRAN program for a personal computer is available (cf. last section of 5.). It computes the maximum likelihood and the Bayesian solution, using approximate formulas in the latter case. Due to these approximations it was possible to develop a Bayesian program which is fast enough to run on a PC. Validation procedures have been performed. The output consists of a print file and, optionally, an ASCII file containing the coordinates of the posterior probability density and distribution functions.

[Following curative resection of colorectal cancer, portal chemotherapy especially benefits non-transfused patients]. / Nach kurativer Resektion colorectaler Carcinome wirkt die portale Chemotherapie vor allem beim nicht-bluttransfundierten Patienten.

After curative resection of colorectal cancer, immediate short-term postoperative intraportal adjuvant chemotherapy reduces the relative risk of recurrence and death in the non-transfused patient significantly, when compared to transfused patients without chemotherapy. This is demonstrated in a multivariate analysis using the Cox model on a group of 469 patients who have been intraoperatively randomized to receive either intraportal chemotherapy for 7 days or no further treatment. The transfused patients with chemotherapy and those receiving neither transfusions nor chemotherapy had a relative risk of recurrence and death situated in between the two groups mentioned above, not statistically different from either of them. In the setting of this study, 7 days postoperative intraportal chemotherapy seems particularly effective in the non-transfused patients.

[Blood transfusion, short perioperative intraportal chemotherapy and recurrence of colorectal cancer]. / Transfusion sanguine, chimiothérapie intraportale périopératoire de courte durée et récidive du cancer colorectal.

Carcinomatous tumors usually have a rather slow proliferation rate. However, this process is sensibly accelerated as soon as immunodepressive phenomena occur. Blood transfusions may result in the appearance of a considerable mass of alloantigens and in simultaneous immunomodulation. On the basis of a series of 469 patients, we are able to realize that the intra-and postoperative administration of blood during the curative resection of colorectal cancers produced a poor prognosis. We also followed up subjects who had had chemotherapy via the portal system for one week but no blood transfusion. The prognosis was definitely better in these patients, and proved to be 2 to 3 times as favorable as for patients receiving blood transfusions without chemotherapy. The various results are thoroughly analyzed, the primary aim being the study of the effects of intraoperative portal chemotherapy. This leads to advocating the restriction of blood transfusions, and the use of autotransfusion or hemodilution if required.