Factors associated with the provision of anti-smoking advice in general practice consultations.

Guidelines urge general practitioners (GPs) to discuss smoking with patients as frequently as possible. Using data collected before and after consultations, this study confirms that GPs are more likely to discuss smoking in the context of smoking-related problems. Encouraging GPs to make greater use of problem-orientated opportunities to discuss smoking may have more effect on rates of advice giving than urging them to advise all smokers.     

Ca2+ imaging of mouse neocortical interneurone dendrites: Ia-type K+ channels control action potential backpropagation

GABAergic interneurones are essential in cortical processing, yet the functional properties of their dendrites are still poorly understood. In this first study, we combined two-photon calcium imaging with whole-cell recording and anatomical reconstructions to examine the calcium dynamics during action potential (AP) backpropagation in three types of V1 supragranular interneurones: parvalbumin-positive fast spikers (FS), calretinin-positive irregular spikers (IS), and adapting cells (AD). Somatically generated APs actively backpropagated into the dendritic tree and evoked instantaneous calcium accumulations. Although voltage-gated calcium channels were expressed throughout the dendritic arbor, calcium signals during backpropagation of both single APs and AP trains were restricted to proximal dendrites. This spatial control of AP backpropagation was mediated by Ia-type potassium currents and could be mitigated by by previous synaptic activity. Further, we observed supralinear summation of calcium signals in synaptically activated dendritic compartments. Together, these findings indicate that in interneurons, dendritic AP propagation is synaptically regulated. We propose that interneurones have a perisomatic and a distal dendritic functional compartment, with different integrative functions.     

Diagnosis of Ovarian Cancer Using Decision Tree Classification of Mass Spectral Data

Recent reports from our laboratory and others support the SELDI ProteinChip technology as a potential clinical diagnostic tool when combined with $n$ -dimensional analyses algorithms. The objective of this study was to determine if the commercially available classification algorithm biomarker patterns software (BPS), which is based on a classification and regression tree (CART), would be effective in discriminating ovarian cancer from benign diseases and healthy controls. Serum protein mass spectrum profiles from 139 patients with either ovarian cancer, benign pelvic diseases, or healthy women were analyzed using the BPS software. A decision tree, using five protein peaks resulted in an accuracy of 81.5% in the cross-validation analysis and 80%in a blinded set of samples in differentiating the ovarian cancer from the control groups. The potential, advantages, and drawbacks of the BPS system as a bioinformatic tool for the analysis of the SELDI high-dimensional proteomic data are discussed.     

Expression of HIF-1 and ubiquitin in conventional renal cell carcinoma: relationship to mutations of the von Hippel-Lindau tumor suppressor gene

Conventional clear cell renal cell carcinomas (cRCC) have mutations of the von Hippel-Lindau (VHL) tumor suppressor gene at 3p25 in approximately 50% of cases. The VHL gene normally regulates ubiquitin-mediated proteolysis of hypoxia-inducible factor 1alpha (HIF-1alpha); in cell lines, VHL inactivation blocks HIF-1alpha proteolysis, resulting in increased HIF-1 expression. This study was undertaken to investigate the relationship between VHL mutations and the expression of ubiquitin and HIF-1alpha in cRCC. Eleven cRCC were studied with microsatellite analysis for 3p deletions and with sequencing for VHL mutations. Immunohistochemistry was performed for HIF-1alpha and ubiquitin. Deletions at 3p25 were found in 10 tumors, and VHL mutations were identified in 6 of these cases. There was staining for ubiquitin and HIF-1alpha in all tumors with VHL mutations. Among the five cases without VHL mutations, staining for ubiquitin or HIF-1alpha was not present in three cases but was present in two tumors, both of which had 3p deletions. The findings support a role for VHL mutations promoting cRCC development by an impairment of HIF-1alpha proteolysis. The findings also suggest that a 3p tumor suppressor gene other than VHL may also influence HIF-1alpha degradation and that there is an additional tumorigenic pathway for cRCC that does not involve VHL or HIF-1.     

Renal disease in type I glycogen storage disease

Although kidney enlargement occurs in Type I glycogen storage disease, renal disease has not been considered a major problem. Death from renal failure in three patients known to us prompted a study of renal function in this disorder. Of the 38 patients with Type I glycogen storage disease under our care, the 18 children under 10 years old had normal renal function. Fourteen of the 20 older patients (13 to 47 years) had disturbed renal function, manifested by persistent proteinuria; many also had hypertension, hematuria, or altered creatinine clearance. Progressive renal insufficiency developed in 6 of these 14 patients, leading to three deaths from renal failure. At the onset of proteinuria, creatinine clearance was increased in seven patients (3.05 +/- 0.68 ml per second per 1.73 m2 of body-surface area; range, 2.47 to 4.13 [normal range, 1.33 to 2.33 ml per second per 1.73 m2]). Renal biopsies were performed in three patients after an average of 10 years of proteinuria. All three biopsies demonstrated focal segmental glomerulosclerosis in various stages of progression. Our data suggest that chronic renal disease is a frequent and potentially serious complication of Type I glycogen storage disease. In addition to treating hypoglycemia vigorously, physicians should monitor renal function carefully in patients with this disorder.     

Novel 5-flucytosine-resistant clade of Candida dubliniensis from Saudi Arabia and Egypt identified by Cd25 fingerprinting

DNA fingerprinting of Candida dubliniensis isolates using the species-specific probe Cd25 previously showed that this species consists of two distinct groups, termed Cd25 group I and Cd25 group II. The present study investigated the population structure of 30 C. dubliniensis oral isolates from Saudi Arabia and Egypt using Cd25 fingerprinting and rRNA gene internal transcribed spacer region-based genotyping. Cd25 fingerprinting analysis of these isolates revealed two distinct populations, the first of which consisted of 10 closely related genotype 1 isolates (average similarity coefficient [S(AB)] value, 0.86). The second population of 20 isolates was much more heterogeneous (average S(AB) value, 0.35) and consisted of two distinct subpopulations, one of which consisted of genotype 3 isolates (n = 13) and the other of genotype 4 isolates (n = 7). A mixed dendrogram generated from the fingerprint data from the 30 Saudi Arabian and Egyptian isolates, 5 Israeli isolates, and 51 previously characterized international isolates (32 of Cd25 group I and 19 of Cd25 group II) revealed the presence of three distinct main clades. The first corresponded to the previously described Cd25 group I and contained all the Saudi Arabian, Egyptian, and Israeli genotype 1 isolates mixed with international isolates. The second clade corresponded to the previously described Cd25 group II and contained three Israeli isolates, one genotype 2 isolate, one genotype 3 isolate, and a genotype 4 variant isolate, which were mixed with international isolates. The third clade has not been described before and consisted solely of the 20 Saudi Arabian and Egyptian genotype 3 and 4 isolates identified in this study and a previously described genotype 4 Israeli isolate. All 20 Cd25 group III isolates exhibited high-level resistance to 5-flucytosine (MIC > or = 128 microg/ml), whereas all Cd25 group I and Cd25 group II isolates tested (10 Saudi Arabian and Egyptian, 16 Israeli, and 24 international) were susceptible to 5-flucytosine (MIC < or = 0.125 microg/ml). The results of this study show for the first time the presence of a novel 5-flucytosine-resistant clade of C. dubliniensis (Cd25 group III) that is predominant among isolates from Saudi Arabia and Egypt and absent from a previously characterized international collection of 98 isolates from 15 countries.     

The characteristics of false negative cervical smears--implications for the UK cervical cancer screening programme

OBJECTIVE: To accurately determine whether there are any features of an abnormal cervical smear that predispose to the production of a false negative report, in order to gain insight into why false negative reports are issued, and to establish whether there are steps that can be taken to reduce them. DESIGN: A quantitative retrospective analysis using the AxioHOME microscope of the number, size, and spatial distribution of abnormal cells in a set of 50 slides comprising a mixture of false negative and true positive cervical smears. SETTING: Five different cytology laboratories in the United Kingdom. RESULTS: False negative smears were found to be quantitatively different from true positive smears. They contained significantly fewer abnormal cells (median number of abnormal cells for false negatives = 173, median number of abnormal cells for true positives = 1712; p < 0.004), and these were more likely to be unevenly distributed on the slide. It was possible to predict with a high degree of accuracy whether a smear was a false negative by analysing number and distribution alone (kappa = 0.57). CONCLUSIONS: False negatives are quantitatively different from true positive cervical smears. This has important implications for quality assurance in the UK cervical screening programme. More consideration needs to be given to the effectiveness of existing quality assurance measures, which need to be tailored to the preferential detection of this type of abnormal cervical smear.     

Facial Muscle Tonus During REM and NREM Sleep

Equipment and procedures were devised for quantifying relatively noise-free recordings of low amplitude chin and lip electromyograms (EMGs) during sleep. A total of 28 REM periods were recorded from 5 young adult female Ss. Tonic EMG levels tended to decline toward their lowest level of the night beginning 5 min in advance of REM periods. With very rare exceptions, the lowest EMG levels of the night were maintained throughout REM sleep. During the 20 min of NREM sleep which followed REM periods, mean EMG levels increased over the REM levels but were lower than those recorded during the 20 min of NREM sleep which preceded the REM periods. This pattern of tonic EMG variation obtained for each of the first 3 REM periods of the night.     

TestPack Chlamydia, a new rapid assay for the direct detection of Chlamydia trachomatis.

TestPack Chlamydia (Abbott Laboratories) is a rapid enzyme immunoassay for the direct antigen detection of Chlamydia trachomatis in endocervical specimens. The assay is self-contained, requires no specialized equipment, and yields results in less than 30 min. The clinical performance of TestPack Chlamydia versus chlamydial cell culture was evaluated with a total of 1,694 paired endocervical specimens. Discordant samples were further investigated by immunofluorescent staining and by Chlamydiazyme immunoassay, with confirmatory procedures. The sensitivity of TestPack Chlamydia with less-than-48-h-old specimens was 76.5%, while culture sensitivity was 86.7%. TestPack Chlamydia specificity was determined to be 99.5%. These results indicate that TestPack Chlamydia is an accurate test for chlamydial infection, with a positive predictive value of 96.2%. This assay is suitable for low-volume chlamydial testing in physician offices, clinics, and smaller laboratories.