Five‐Year Follow‐up After Sacral Neuromodulation: Single Center Experience

Objective. We studied long‐term clinical efficacy of sacral neuromodulation (SNM) therapy in patients with refractory urgency incontinence (UI), urgency/frequency (UF) and voiding difficulty (VD), together with urodynamic data at baseline and six   months postimplant. Materials and Methods. Twenty‐two patients were implanted with a neurostimulator after a positive response to a percutaneous nerve evaluation test defined as a greater than 50% improvement in symptoms. Results. At five‐year follow‐up, the number of incontinent episodes and pad usage per day decreased significantly in 10 out of 15 UI patients. Two of five UF patients were successfully treated with SNM; the number of daily voids for all UF patients decreased from 25 to 19 and average voided volume increased from 98 to 212 mL. One of the two VD patients was able to void to completion. Mean first sensation of filling at the six‐month urodynamic investigation for the UI and UF patients increased from 78 to 241 mL and 141 to 232 mL, respectively, and the maximum bladder capacity increased from 292 to 352 mL and 223 to 318 mL, respectively. Five of 22 patients underwent device explant and one patient still has an inactive stimulator implanted. Conclusion. SNM is an effective treatment modality that offers sustained clinical benefit in the majority of patients with refractory UI, UF, and VD that do not respond to other, more conservative therapies.     

High resolution microarray comparative genomic hybridisation analysis using spotted oligonucleotides

BACKGROUND: Currently, comparative genomic hybridisation array (array CGH) is the method of choice for studying genome wide DNA copy number changes. To date, either amplified representations of bacterial artificial chromosomes (BACs)/phage artificial chromosomes (PACs) or cDNAs have been spotted as probes. The production of BAC/PAC and cDNA arrays is time consuming and expensive. AIM: To evaluate the use of spotted 60 mer oligonucleotides (oligos) for array CGH. METHODS: The hybridisation of tumour cell lines with known chromosomal aberrations on to either BAC or oligoarrrays that are mapped to the human genome. RESULTS: Oligo CGH was able to detect amplifications with high accuracy and greater spatial resolution than other currently used array CGH platforms. In addition, single copy number changes could be detected with a resolution comparable to conventional CGH. CONCLUSIONS: Oligos are easy to handle and flexible, because they can be designed for any part of the genome without the need for laborious amplification procedures. The full genome array, containing around 30000 oligos of all genes in the human genome, will represent a big step forward in the analysis of chromosomal copy number changes. Finally, oligoarray CGH can easily be used for any organism with a fully sequenced genome.     

Retroversion of the humeral head in children with an obstetric brachial plexus lesion

We undertook a prospective MRI study to measure the retroversion of the humeral head in 33 consecutive infants with a mean age of 1 year 10 months (3 months to 7 years 4 months) who had an obstetric brachial plexus lesion (OBPL). According to a standardised MRI protocol both shoulders and humeral condyles were examined and the shape of the glenoid and humeral retroversion determined. The mean humeral retroversion of the affected shoulder was significantly increased compared with the normal contralateral side (-28.4 +/- 12.5 degrees v -21.5 +/- 15.1 degrees, p = 0.02). This increase was found only in the children over the age of 12 months. In this group humeral retroversion was -29.9 +/- 12.9 degrees compared with -19.6 +/- 15.6 degrees in the normal shoulder (p = 0.009), giving a mean difference of 10.3 degrees (95% confidence interval 3.3 to 17.3). This finding is of importance when considering the operative treatment for subluxation of the shoulder in children with an OBPL.     

Measuring human cardiac tissue sodium concentrations using surface coils, adiabatic excitation, and twisted projection imaging with minimal T2 losses

PURPOSE: To measure tissue sodium concentrations in the human heart with (23)Na MRI using a surface coil, thereby eliminating the effects of inhomogeneous excitation by surface coils and minimizing T(1) and T(2) relaxation. MATERIALS AND METHODS: We combined fully relaxed, very short-echo, (23)Na twisted projection imaging (TPI) with adiabatic half passage (AHP) excitation and external referencing on subjects and comparing with a concentration reference phantom scan to quantify TSC with surface coils. (23)Na signal losses during hard (square), composite, and tanh/tan amplitude/frequency-modulated AHP excitation pulses were analyzed over a wide range of RF field strengths and T(2short) values. RESULTS: AHP excitation yielded a homogeneous excitation flip angle and negligible losses compared to a 90 degrees hard pulse wherever the B1 field exceeded the adiabatic threshold, rendering this sequence suitable for applications that use surface coil excitation. An AHP (23)Na TPI sequence was used with a surface coil at 1.5 T to noninvasively quantify myocardial TSC in 10 normal volunteers. The mean TSC was 43 +/- 4, 53 +/- 12, and 17 +/- 4 micromol/g in the left ventricular (LV) free wall, septum, and adipose tissue, respectively, consistent with prior invasive measurements on biopsy and autopsy specimens. CONCLUSION: It is now possible to noninvasively quantify TSC in the human heart with surface coil (23)Na MRI.     

Large-scale, acute, bacterial gastroenteritis caused by the enterotoxin of Staphylococcus aureus after a barbecue

EPIDEMIOLOGICAL OBSERVATION: On a warm day, during a barbecue that was attended by over 100 guests, a large number became rapidly ill with signs of acute gastroenteritis within a few hours after eating the prepared food. The characteristic symptoms were nausea, vomiting, syncope and in some cases in a later stage, diarrhoea. Sixty patients were transferred to hospitals. INVESTIGATION: Investigation revealed that the cause of this outbreak of gastroenteritis was an enterotoxin-A-producing strain of Staphylococcus aureus in a noodle dish. Both the food residues and the faeces from patients contained genotypically identical strains of S. aureus. They all had the gene for the gastroenteritis-inducing enterotoxin A from S. aureus. CONCLUSION: This case shows that the timely involvement of the different health authorities responsible for intervening in explosions of food poisoning is crucial for the clarification and treatment of such large-scale outbreaks. In the investigation of this outbreak, the municipal health authority co-operated with regional laboratories and the Food and Consumer Product Safety Authority/Inspectorate for Health Protection and Veterinary Public Health.     

Clinical Trials Do Not Use Random Samples Anymore

Current clinical trials do not use random samples, but, instead, convenience samples. This raises the risk of non-normal data.

The aim of this paper is to review and describe for a non-mathematical readership common methods for testing the normal property, as well as methods for analyzing the data in case of non-normality.

With slight departures from the normal distribution, normality tests can be used even so. They include, among other tests, the normal-, t-, chi-square- tests, analysis of variance, and regression analyses. They should not be used if the chi-square goodness of fit is significant. Rank-testing is, then, an alternative, but, sometimes, distributions do not allow for this approach either. This can be checked by the Kolmogorov-Smirnov test. If the latter test is also positive, rank-testing is not warranted, and confidence intervals can be derived from the data without prior assumption about the type of frequency distribution. This can be done by calculating the range within which 95% of all possible outcomes lie. Another popular method for this purpose is bootstrapping, which resamples at random from the study's own data. This paper reviews methods to assess data for compliance with normality, and summarizes solutions for the analysis of non-normal data. We strongly believe that normality statistics, although the mainstay of statistical analysis for centuries, will rapidly be replaced with non-normal testing as the awareness of non-normal sampling distributions grows, and we hope that the paper will strengthen this awareness and affect the design and analysis of future clinical trials.     

Bell-like homeodomain selectively regulates the high-irradiance response of phytochrome A

Plant responses mediated by phytochrome A display a first phase saturated by transient light signals and a second phase requiring sustained excitation with far-red light (FR). These discrete outcomes, respectively so-called very-low-fluence response (VLFR) and high-irradiance response (HIR), are appropriate in different environmental and developmental contexts but the mechanisms that regulate the switch remain unexplored. Promoter analysis of a light-responsive target gene revealed a motif necessary for HIR but not for VLFR. This motif is required for binding of the Bell-like homeodomain 1 (BLH1) to the promoter in in vitro and in yeast 1-hybrid experiments. Promoter substitutions that increased BLH1 binding also enhanced HIR. blh1 mutants showed reduced responses to continuous FR and to deep canopy shadelight, but they retained normal responses to pulsed FR or red light and unfiltered sunlight. BLH1 enhanced BLH1 expression and its promotion by FR. We conclude that BLH1 specifically regulates HIR and not VLFR of phytochrome A.