Autosomal dominant cone-rod dystrophy due to a missense mutation (R838C) in the guanylate cyclase 2D gene (GUCY2D) with preserved rod function in one branch of the family

Autosomal recessive retinitis pigmentosa (ARRP) is a degenerative disorder of photoreceptors. Mutations in several genes encoding different proteins of the visual cascade are described. The inheritance of two intragenic markers within the interstitial retinol binding protein (IRBP) gene was established in 45 Spanish families with a history of ARRP. Homozygosity mapping and cosegregation analyses were positive in 19 families. Only one heterozygous T-C transition at position 3024 (exon 1) was detected in one consanguineous family. This variant was identified as a rare polymorphism and was present in 5% of the chromosomes analyzed.     

Enterohepatic Circulation,Urinary Excretion and Laxative Action of Some Bisacodyl Derivatives after Intragastric Administration in the Rat

Abstract: Bisacodyl (BIS), the parent diphenol (DES) and its sulphuric acid di-ester (picosulphate = PICO) were given by stomach tube to fasted rats at a dose of 3.1 μmol/100 g rat. Bile was sampled in the periods 0–6, 6–12 and 12–18 hrs after drug administration, and assayed for total diphenol (= free + conjugated) by HPLC. Mean fractions (% of dose±S.E.M.) excreted in 5 rats per compound and period were: BIS 74.0±4.7, 51.9±7.9 and 30.8±2.5; DES 41.2±4.3, 46.8±4.7 and 25.1±2.5; PICO 9.0±0.9, 26.0±5.4 and 19.6±3.1. Only minor amounts were excreted as free diphenol. Urine samples taken by bladder puncture and assayed as above furthermore showed that the renal excretion of total diphenol was insignificant compared to the amounts excreted in bile. Practically no diphenol was present in urine 0–6 hrs after the administration of PICO. In experiments with BIS and DES at 0.85 μmol/100 g, total diphenol excreted in bile during 0–6 hrs was: BIS 67.1±2.6 (n = 5); DES: 55.4±3.0 (5). - The latency time for laxative effect was studied in groups of 10 unfasted rats per compound. Cumulative time response curves showed that PICO caused diarrhoea more promptly at 0.85 μmol/100 g than either BIS or DES. In most rats, this delayed action of BIS and DES persisted also at 1.7 μmol/100 g. At 3.1 μmol/100 g, however, the majority of the rats reacted as promptly to these two compounds as to PICO. These results are discussed in relation to the biliary excretion experiments, and interpreted in terms of the relative importance at the different dose levels of: 1. The enterohepatic recirculated fraction, and 2. The non-absorbed fraction, which passes directly to the large intestine. For PICO, the latter fraction is the single determinant of the effect, which is triggered when the di-ester is being hydrolyzed to active diphenol in this part of the GI-tract.     

Overexpression and involvement in migration by the metastasis-associated phosphatase PRL-3 in human myeloma cells

Multiple myeloma (MM) is characterized by accumulation and dissemination of malignant plasma cells (PCs) in the bone marrow (BM). Gene expression profiling of 2 MM cell lines (OH-2 and IH-1) indicated that expression of PRL-3, a metastasis-associated tyrosine phosphatase, was induced by several mitogenic cytokines. Cytokine-driven PRL-3 expression could be shown in several myeloma cell lines at both the mRNA and protein levels. There was significantly higher expression of the PRL-3 gene in PCs from patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma (SMM), and myeloma than in PCs from healthy persons. Among 7 MM subgroups identified by unsupervised hierarchical cluster analysis, PRL-3 gene expression was significantly higher in the 3 groups denoted as "proliferation," "low bone disease," and "MMSET/FGFR3." PRL-3 protein was detected in 18 of 20 BM biopsies from patients with MM. Silencing of the PRL-3 gene by siRNA reduced cell migration in the MM cell line INA-6, but had no detectable effect on proliferation and cell-cycle phase distribution of the cells. In conclusion, PRL-3 is a gene product specifically expressed in malignant plasma cells and may have a role in migration of these cells.     

Sleep apnoea, anxiety, depression and somatoform pain: a community-based high-risk sample

Community-based studies that measure both psychiatric diagnoses and obstructive sleep apnoea (OSA) are lacking. This study reports current psychiatric disorders in community-dwelling adults at high risk for OSA identified by the Berlin Questionnaire. Furthermore, associations between OSA and current psychiatric disorders, unadjusted and adjusted for putative confounders, are reported. A subsample of the Akershus Sleep Apnoea Project consisting of 290 adults, aged 30-65 yrs, with positive Berlin Questionnaire screening underwent the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, version IV and polysomnography. Auxiliary analyses of depression are provided. The median apnoea/hypopnoea index score in the sample was 7.7 (interquartile range 2.4-22.2). Major depressive disorder, current anxiety and somatoform pain disorder were diagnosed in 12.4%, 14.8% and 19.3% of participants, respectively. At least one psychiatric disorder was diagnosed in 110 participants. The odds ratio of participants with OSA having a psychiatric disorder compared with participants without OSA was 0.54 (95% CI 0.33-0.88). A negative association did not exist among Berlin Questionnaire low-risk participants. In conclusion, more than one-third of participants in a community-based, Berlin Questionnaire high-risk sample were diagnosed with a psychiatric disorder. A negative association between OSA and psychiatric morbidity was found.     

Neuronavigation by intraoperative three-dimensional ultrasound: initial experience during brain tumor resection

OBJECTIVE: Three-dimensional (3-D) ultrasound is an intraoperative imaging modality used in neuronavigation as an alternative to magnetic resonance imaging (MRI). This article summarizes 4 years of clinical experience in the use of intraoperative 3-D ultrasound integrated into neuronavigation for guidance in brain tumor resection. METHODS: Patients were selected for inclusion in the study on the basis of the size and location of their lesion. Preoperative 3-D MRI data were registered and used for planning as in other conventional neuronavigation systems. Intraoperative 3-D ultrasound images were acquired three to six times, and tumor resection was guided on the basis of these updated 3-D images. RESULTS: Intraoperative 3-D ultrasound represents a good solution to the problem of brain shift in neuronavigation because it easily provides an updated, and hence more accurate, map of the patient's true anatomy in all phases of the operation. Ultrasound makes it possible to follow the progression of the operation, and it improves the radicality of tumor resection by detecting tumor tissue that would remain if the imaging technology had not been used (in 53% of the cases). Integration of 3-D ultrasound with navigation technology solves the orientation problem experienced previously with two-dimensional ultrasound in neurosurgery. The technology makes it possible to directly compare intraoperative ultrasound and MRI data regarding visualization of the lesion. Ultrasound image quality is useful for guiding surgical procedures. CONCLUSION: Intraoperative 3-D ultrasound seems to provide a time- and cost-effective way to update high-quality 3-D maps used in neuronavigation.     

Quality of life, pain, and psychological well-being in women suffering from gynecological disorders

Most gynecological disorders are not life threatening. They may nevertheless severely affect women's lives. This study was conducted to investigate quality of life (QOL), pain, and psychological well-being in women suffering from such disorders compared with a control group. Women with benign gynecological disorders who are awaiting hysterectomy have a lower score in the health and functioning domain of QOL compared with the control group. More than three of four patients experience pain, mostly pelvic pain. Pain has a clear negative influence on women's QOL, pelvic pain to a greater degree than other types of pain. The patients report the same degree of psychological well-being as the control group. Benign gynecological disorders have a clear negative impact on women's health and functioning, and pain is a major problem for these patients. The more pain, the lower QOL. Their psychological well-being, however, does not seem to be affected.     

The quality of life in women suffering from gynecological disorders is improved by means of hysterectomy. Absolute and relative differences between pre- and postoperative measures

BACKGROUND: Gynecological disorders can have adverse effects on a woman's quality of life. Most hysterectomies are thus performed to enhance women's quality of life rather than to save life. This study aims at evaluating the long-term impact of hysterectomy on this outcome variable. METHODS: The quality of life in 111 women undergoing hysterectomy for benign reasons was tested before, and six and twelve months after, the operation. A control-group of non-hysterectomized women from the normal population was tested once. Ferrans & Powers' Quality of Life Index, consisting of four life domains, was used. This index has a pre-set highest possible obtainable score. For the subjects with a high pre-test score, there was little scope for further measurable improvement after hysterectomy, which gives a false stability in the material. A method for calculating the relative differences was introduced. RESULTS: The health and functioning domain of the quality of life among women awaiting hysterectomy is significantly lower compared to that of the control-group (p<.01) Both six and twelve months after the hysterectomy, the patients have reached the same level of their health and functioning as the control-group. Using the relative difference-form, it is demonstrated that the subjects have obtained significantly higher levels in all the domains of quality of life after hysterectomy. CONCLUSIONS: The results of this study show that hysterectomy is associated with a positive long-term impact on a woman's quality of life.