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Clinical significance of beta 2-glycoprotein I-dependent anticardiolipin antibodies in the reproductive autoimmune failure syndrome: correlation with conventional antiphospholipid antibody detection systems.

OBJECTIVE: Our purpose was to determine whether beta 2-glycoprotein I-dependent anticardiolipin antibodies may represent a superior marker of reproductive risk than do conventional antiphospholipid antibodies. STUDY DESIGN: The incidence of beta 2-glycoprotein I-dependent and beta 2-glycoprotein I-independent anticardiolipin antibodies and of six conventional antiphospholipid antibodies was statistically compared between study groups with and without autoantibody-associated features of reproductive failure. Sera from 356 women were randomly selected from the frozen sera bank at the Center for Human Reproduction, Chicago. They included sera from 259 patients with autoantibody-associated features of reproductive failure such as unexplained infertility, endometriosis, and repeated pregnancy loss and 97 infertile controls. Autoantibody levels by a modified enzyme-linked immunosorbent assay for beta 2-glycoprotein I-dependent and beta 2-glycoprotein I-independent anticardiolipin antibodies and a standard enzyme-linked immunosorbent assay for anticardiolipin antibody and five other antiphospholipid antibodies were then compared. RESULTS: Patients demonstrated a significantly higher incidence of beta 2-glycoprotein I-dependent anticardiolipin antibodies (5.4%) than did controls (0%) in a modified enzyme-linked immunosorbent assay (p = 0.01). No such difference was, however, noted for beta 2-glycoprotein I-independent anticardiolipin antibodies or any one of six antiphospholipid antibodies. Two or more among six antiphospholipid antibodies, especially if involving anticardiolipin antibodies, antiphosphatidylserine and antiphosphatidylinositol, as assayed by standard enzyme-linked immunosorbent assay, were significantly more often (p = 0.02) positive in the patients (5.0%) than in the controls (0%). Moreover, positivity in two of those three antiphospholipid antibodies correlated in 59% of cases to positivity in the beta 2-glycoprotein I-dependent anticardiolipin antibody. CONCLUSIONS: As a single test beta 2-glycoprotein I-dependent anticardiolipin antibody appears to be superior to cofactor-independent anticardiolipin antibody or any other single conventional antiphospholipid antibody for the detection of autoantibody-associated conditions of reproductive failure. A broadly based panel of conventional antiphospholipid antibodies, especially if inclusive of anticardiolipid antibody, antiphosphatidylserine, and antiphosphatidylinositol, may, however, achieve similar results.

Abortion, Habitual↗

Impaired nonrestricted cytolytic activity in systemic lupus erythematosus: involvement of a pathway independent of Fas, tumor necrosis factor, and extracellular ATP that is associated with little detectable perforin.

OBJECTIVE: To determine the cytolytic effector pathway involved in impaired generation of nonrestricted cytolytic activity in systemic lupus erythematosus (SLE). METHODS: Peripheral blood mononuclear cells (PBMC) from normal subjects and SLE patients were stimulated in vitro with anti-CD3 monoclonal antibody (MAb) and interleukin-2 to promote the generation of nonrestricted cytolytic activity. On day 13 of culture, the PBMC were assayed for cytolytic activity against Fas-Daudi cells and Fas+ Jurkat cells. The effects on cytotoxicity of calcium chelation, antagonist anti-Fas MAb, tumor necrosis factor (TNF) alpha and beta, and ATP were measured. Intracellular perforin expression was determined by intracellular staining, and perforin messenger RNA levels were determined by quantitative competitive reverse transcription-polymerase chain reaction. RESULTS: We demonstrated the existence of a cytolytic pathway that is independent of Fas, TNF alpha, TNF beta, and ATP, but is dependent upon extracellular calcium. Despite its calcium dependence, this pathway is associated with low-to-undetectable levels of perforin. CONCLUSION: Impaired generation of nonrestricted cytolytic activity in SLE is likely due to decreased activity of this Fas-, TNF alpha-, TNF beta-, ATP-independent pathway associated with very low levels of perforin.

Adenosine Triphosphate↗

Natural history and long-term outcome of cardiac rhabdomyomas detected prenatally.

OBJECTIVES: To analyse the data of fetal cases with rhabdomyomatosis, the growth of masses in utero, and the relative outcome. MATERIAL AND METHODS: Thirteen cases of cardiac/pericardial tumours with characteristics suggesting rhabdomyomatosis were found in our centre on fetal echocardiography, five before 24 wg (group A) and eight (group B) at 25 to 36 wg. Four patients terminated the pregnancy, nine continued the pregnancy and were followed-up until delivery and after birth (median postnatal follow-up of 4.2 years, range 18 months-16 years). RESULTS: In six/nine cases that continued the pregnancy (66.7%), the growth of smaller tumor masses was proportional with gestational age until 30 to 32 wg and was stable after that. In three cases, larger masses grew disproportionally and other small masses were revealed, causing a partial obstruction of outflow tracts. After birth, no case required surgery and no serious rhythm problems occurred. Cardiac masses regressed at least partially in all cases. Tuberous sclerosis was diagnosed in 9/11 cases (81.1%) investigated by magnetic resonance imaging in utero or postnatally. One case also had bilateral polycystic kidneys. CONCLUSIONS: Multiple and larger noduli progressed disproportionally in utero, until 30 to 36 wg. No relevant cardiac problems occurred after birth and the masses regressed in all cases. The high frequency of association with tuberous sclerosis is confirmed in our series.

Female↗

Improving the accuracy of carbon-to-hydrogen ratio determination for P, N, S, O, Cl, and Br-containing organic compounds using atomic emission detection.

The objective of this work was to investigate the dependence of atomic emission detector C and H response on microwave-induced plasma conditions and to improve the accuracy of carbon-to-hydrogen ratio determination for trialkylphosphates, herbicides, chlorophenols, and sulfur-containing organic compounds. Compounds which differed structurally from the analytes were used as reference compounds. It was found that when the oxygen concentration in the helium was the maximum for the instrument (9%) relative errors in carbon-to-hydrogen ratio determination were 3-8%, irrespective of analyte and reference compound structure, whereas when working in the mode of operation recommended by the manufacturer of the instrument (1.5% oxygen in helium) the respective errors were 10-20% or higher. This improvement in the accuracy of carbon-to-hydrogen ratio determination was accompanied by a factor of ten decrease in sensitivity.

Journal Article↗

FCCP is cardioprotective at concentrations that cause mitochondrial oxidation without detectable depolarisation.

OBJECTIVE: The role of mitochondria and in particular of mitochondrial uncoupling in the mechanism of cardioprotection is not defined. In the accompanying paper we have shown that pretreatment of isolated rat hearts with a low concentration (100 nM) of FCCP, prior to global ischaemia, is cardioprotective, while 300 nM FCCP exacerbates injury. Here we define the mitochondrial responses to increasing concentrations of FCCP and also to explore the equivalence of the cardioprotective doses of diazoxide. METHODS: Changes in mitochondrial respiration in response to FCCP and diazoxide were determined in isolated rat ventricular myocytes. In addition, mitochondrial state was monitored using confocal microscopy to record mitochondrial potential (TMRM) and redox state (NADH) during FCCP and diazoxide treatment. Myocytes were also voltage-clamped and whole cell currents recorded in response to 100 nM FCCP. RESULTS: FCCP (10-1000 nM) caused significant dose-dependent increase in oxygen consumption. Diazoxide (30 microM) failed to cause any measurable change in mitochondrial function. FCCP at 100 nM caused mitochondrial oxidation, but no change in mitochondrial membrane potential or (sarc)K(ATP) channel current, while at 300 nM, FCCP caused significant mitochondrial depolarisation. Diazoxide failed to induce any mitochondrial oxidation or depolarisation. CONCLUSIONS: Concentrations of FCCP that cause mitochondrial oxidation without depolarisation are cardioprotective. Higher FCCP concentrations dissipate mitochondrial membrane potential and exacerbate injury. This establishes the principle that mild mitochondrial uncoupling activates a protective mechanism. Diazoxide did not cause mitochondrial oxidation or mitochondrial depolarisation, suggesting it induces protection via another mechanism.

Animals↗

Cervicography as an adjunctive test to visual inspection with acetic acid in cervical cancer detection screening.

OBJECTIVE: Validate Digital Cervicography as adjunctive cervical cancer screening test to VIA and Cytology. METHOD: Women (1292) were submitted to both cytological and VIA tests to obtain a sample of 301 positive VIA cases (23.3%) which have had the Digital Cervicography (DC) taken and evaluated. Just cases considered positive by DC (149/301 cases--49.5%) and/or positive Pap smear tests were referred to colposcopy and biopsy whenever indicated. RESULTS: Cervical smear was positive in 5.4%, including LGSIL (4%), HGSIL (1%) and one case of invasive cancer (0.4%), and 1.6% of ASCUS or AGUS). DC identified 81 positive cases (74 LGSIL; 5 HGSIL; 2 cancers). The sensitivity of cytology was 14.8%, and the DC was 100%. Corresponding specificities were 95.4% and 69.1%, respectively. The NPV and PPV for DC were 100% and 54.4%. CONCLUSION: DC increases sensitivity, specificity and positive predictive value of VIA, becoming a valid adjunctive screening test for cervical cancer in low resource settings.

Acetic Acid↗

Emergency department assessment of abdominal pain: clinical indicator tests for detecting peritonism.

OBJECTIVES: Peritonism is a finding that leads to a more cautious approach in the emergency department management of abdominal pain. This study examined whether peritonism assessment using inspiration, expiration and cough tests was associated with the patient's clinical management. METHODS: This prospective observational study evaluated consecutive patients presenting directly to the emergency department for 3 months from June 2000 with abdominal pain. Triage initial observations of blood pressure, pulse, respiratory rate, oxygen saturation and temperature were recorded. The examining emergency physician recorded each patient's response and pain score to the individual peritonism tests and scored it as positive if there was an indication of it being a painful manoeuvre. The results were blinded from the receiving specialty if subsequent referral was required. RESULTS: Sixty-seven patients had peritonism tests performed. No individual test was more painful than the others with similar values in pain scores. In all, 70% (7/10) were admitted when all three tests were positive, compared with 21% (12/57) when two or less of the tests scored positive (P=0.004, Fisher's exact test). Admission was not associated with any individual test or combination of tests, or any other variable. The peritonism tests were not associated with any other physiological observation or measurement. CONCLUSIONS: These peritonism tests represent a simple investigation, and are significantly associated with admission when all three tests are positive. They seem to be a clinical predictor of cases in which continuing assessment was required, and may be useful as a departmental 'safety net' in the management of abdominal pain.

Abdominal Pain↗

Radical parametrectomy for occult cervical carcinoma detected posthysterectomy.

OBJECTIVE: There are no randomized studies of the two therapeutic alternatives (surgery or radiotherapy) for occult cervical carcinoma, and survival rates in the absence of residual cancer seem to be similar for both. This article presents our experience with radical reoperation for occult cervical carcinoma. MATERIALS AND METHODS: Eleven patients with occult cervical cancer, primary invasive tumor >/=0.5 cm and </=3.0 cm, free margins in the hysterectomy specimen, and absence of clinically evident residual tumor were reoperated (radical parametrectomy with partial colpectomy and pelvic lymphadenectomy). RESULTS: Histopathologic examination after reoperation showed no evidence of residual disease in nine cases and metastasis in lymph nodes in two cases, one of them with parametrial involvement. Survival was 100% among disease-free cases on reoperation and 0% in cases with residual disease (5-year follow-up). CONCLUSIONS: Radical reoperation allows disease staging, sorting of patients into risk groups, and avoidance of radiation therapy in more than two thirds of the cases of occult cervical carcinoma.

Journal Article↗

Activated partial thromboplastin time waveform analysis: a new tool to detect infection?

OBJECTIVE: An abnormality of the optical transmission waveform obtained during measurement of the activated partial thromboplastin time (aPTT) has been described to identify a high-risk intensive care unit population consisting of patients with sepsis or with higher mortality rates than patients with normal aPTT waveforms. We investigated the abnormal aPTT biphasic waveform as a diagnostic and prognostic marker of infection. DESIGN: Prospective, observational study investigating the predictive value of aPTT waveform analysis for the diagnosis and prognosis of sepsis. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: We studied 187 consecutive patients who fulfilled at least two or more criteria of the systemic inflammatory response syndrome at admission or during intensive care stay and classified as having systemic inflammatory response syndrome, sepsis, severe sepsis, or septic shock during an 8-month period. INTERVENTIONS: Laboratory analyses including aPTT waveform analysis and procalcitonin and C-reactive protein concentrations were measured at days 1-3. MEASUREMENTS AND MAIN RESULTS: The final diagnoses were systemic inflammatory response syndrome in 49%, sepsis in 16%, severe sepsis in 12%, and septic shock in 23% of patients. On day 1, the biphasic waveform was significantly more abnormal in patients with severe sepsis or septic shock than in patients with systemic inflammatory response syndrome or sepsis. The biphasic waveform was more accurate than procalcitonin and C-reactive protein for differentiating patients with severe sepsis and septic shock, with 90% sensitivity and 92% negative predictive value. Biphasic waveform values were significantly more abnormal during days 1-3 in septic nonsurvivors than in survivors and nonseptic nonsurvivors. The biphasic waveform exhibited the best specificity (91%) and negative predictive value (98%) for the prognosis of sepsis-related mortality on day 3. CONCLUSIONS: In intensive care units, when the analyzer is available, aPTT waveform analysis is an inexpensive, rapid, effective, and readily available tool providing information for the diagnosis of severe sepsis and the prognosis of septic patients.

Adult↗

The curative role of radiotherapy in patients with isolated para-aortic node recurrence from cervical cancer and value of squamous cell carcinoma antigen for early detection.

The objective of this study was to examine the clinical benefits of routine squamous cell carcinoma antigen (SCC-ag) monitoring of patients with locally advanced cervical cancer. Recurrent disease occurred in 99 uterine cervical cancer patients with elevated pretreatment SCC-ag before primary radiotherapy. Elevated SCC-ag levels persisted in 23 patients after primary radiotherapy (group 1), and SCC-ag was normalized in 76 patients after primary radiotherapy (group 2). The overall survival (OS) rate was higher for patients with SCC-ag elevation as the first sign than for patients with recurrence predicted by other modalities for group 2 patients (P = 0.033). The prediction of isolated para-aortic node recurrence significantly correlated with SCC-ag elevation as an initial sign (P = 0.001). The SCC-ag level before primary radiotherapy (> or = 10.8 ng/mL) significantly affected recurrence predicted by SCC-ag elevation as an initial sign (P = 0.002). For multivariate analysis, the presence of para-aortic node recurrence was statistically significant in OS (P < 0.0001). Routine SCC-ag monitoring of patients with carcinoma of the uterine cervix can lead to the early diagnosis of isolated para-aortic lymph node recurrence, and prolonged survival can be achieved by applying radiation therapy to the para-aortic region. To reduce the number of patients monitored for SCC-ag, we recommend monitoring group 2 patients with pretreatment SCC-ag level before primary radiotherapy > or = 10.8 ng/mL.

Adult↗

Permanence of Fungi-Fluor epifluorescence stain to detect microsporidia.

OBJECTIVE: Epifluorescence microscopy, a methodology for the screening of bodily fluids and tissue specimens for microsporidia species, was directed to evaluate the retention of epifluorescence of fixed and stained specimens over time. METHODS: Thirty samples of stool, bodily fluids, duodenal touch preparations, and biopsies, were tested for the retention of their epifluoresence using the Fungi-Fluor procedure. Specimens were examined under a 330- to 380-nm UV filter at the time of preparation, 3 wk later, and then at monthly intervals for 18 months. All specimens were reevaluated for the presence or absence of fluorescence and any decrement of fluorescence over time. No special preservation techniques were used on any of the slides. RESULTS: All 30 specimens maintained their epifluorescence from the time of slide preparation to 18 month later. No decrement in fluorescence was noted in any sample examined. Accuracy and ease of spore identification was maintained. CONCLUSIONS: Epifluorescence microscopy demonstrates the utility of this technique for archival study of microsporidia-containing specimens over prolonged periods of time.

Animals↗

Incidence among men of asymptomatic abdominal aortic aneurysms: estimates from 500 screen detected cases.

OBJECTIVES: To determine the incidence of asymptomatic abdominal aortic aneurysms and the implications for an ultrasound screening programme in England and Wales. METHODS: First screen data were obtained from the Chichester and Huntingdon screening studies and used to estimate the prevalence of abdominal aortic aneurysms. The incidence of new, asymptomatic aneurysms was estimated from the prevalence rates observed in the Huntingdon screening study. SETTING: Screening programmes in Huntingdon and Chichester using ultrasound to screen all men over the age of 50 and men over age 65 respectively. RESULTS: The prevalence of abdominal aortic aneurysms ranged between 5.32% and 8.02% and between 6.18% and 9.88% of men aged between 65 and 79 in Chichester and Huntingdon respectively. Annual incidence rates, estimated by age, rose steadily reaching a peak of 0.67% of the Huntingdon population per year at age 65. Thereafter incidence falls. Estimates of the incidence of new asymptomatic abdominal aortic aneurysms, based on the observed prevalence data, were calculated and showed a peak at age 65. CONCLUSIONS: Hypotheses are offered to explain this unexpected early peak in incidence. This information should allow the definition of the optimum age for screening, and the relative benefits of screening at different intervals if widespread screening is adopted in the future.

Age Factors↗

Errors in general practice: development of an error classification and pilot study of a method for detecting errors.

OBJECTIVE: To describe a classification of errors and to assess the feasibility and acceptability of a method for recording staff reported errors in general practice. DESIGN: An iterative process in a pilot practice was used to develop a classification of errors. This was incorporated in an anonymous self-report form which was then used to collect information on errors during June 2002. The acceptability of the reporting process was assessed using a self-completion questionnaire. SETTING: UK general practice. PARTICIPANTS: Ten general practices in the North East of England. MAIN OUTCOME MEASURES: Classification of errors, frequency of errors, error rates per 1000 appointments, acceptability of the process to participants. RESULTS: 101 events were used to create an initial error classification. This contained six categories: prescriptions, communication, appointments, equipment, clinical care, and "other" errors. Subsequently, 940 errors were recorded in a single 2 week period from 10 practices, providing additional information. 42% (397/940) were related to prescriptions, although only 6% (22/397) of these were medication errors. Communication errors accounted for 30% (282/940) of errors and clinical errors 3% (24/940). The overall error rate was 75.6/1000 appointments (95% CI 71 to 80). The method of error reporting was found to be acceptable by 68% (36/53) of respondents with only 8% (4/53) finding the process threatening. CONCLUSION: We have developed a classification of errors and described a practical and acceptable method for reporting them that can be used as part of the process of risk management. Errors are common and, although all have the potential to lead to an adverse event, most are administrative.

Attitude of Health Personnel↗

Genome sharing in large pedigrees: multiple imputation of ibd for linkage detection.

Our objective is the development of robust methods for assessment of evidence for linkage of loci affecting a complex trait to a marker linkage group, using data on extended pedigrees. Using Markov chain Monte Carlo (MCMC) methods, it is possible to sample realizations from the distribution of gene identity by descent (IBD) patterns on a pedigree, conditional on observed data YM at multiple marker loci. Measures of gene IBDW which capture joint genome sharing in extended pedigrees often have unknown and highly skewed distributions, particularly when conditioned on marker data. MCMC provides a direct estimate of the distribution of such measures. Let W be the IBD measure from data YM, and W* the IBD measure from pseudo-data Y*M simulated with the same data availability and genetic marker model as the true data YM, but in the absence of linkage. Then measures of the difference in distributions of W and W* provide evidence for linkage. This approach extracts more information from the data YM than either comparison to the pedigree prior distribution of W or use of statistics that are expectations of W given the data YM. A small example is presented.

Chromosome Mapping↗

Acute appendicitis in children: value of sonography in detecting perforation.

OBJECTIVE: We determined the sonographic features of perforating appendicitis in children in order to determine the best criteria for establishing the diagnosis. MATERIALS AND METHODS: Sonograms of the right lower quadrants of 71 children with proved appendicitis were reviewed to determine the value of sonography in distinguishing between nonperforating and perforating appendicitis. The sonographic signs evaluated included the presence or absence of an appendix, an echogenic submucosal layer, increased periappendiceal echogenicity, free or loculated periappendiceal or pelvic fluid collections, and appendicoliths. The sonographic findings were correlated with the surgical and pathologic findings. RESULTS: Forty-five patients had nonperforating appendicitis, and 26 had perforating appendicitis. A sonographically visible appendix was present in all patients with nonperforating appendicitis and in 10 (38%) of 26 patients with perforation. An echogenic submucosa was noted in 27 (60%) of 45 patients with uncomplicated appendicitis but in only three (30%) of 10 patients with a visible appendix and perforating appendicitis (p < .05). In 19 of 26 patients with perforating appendicitis, sonography showed loculated periappendiceal or pelvic fluid collections; no patient with nonperforating appendicitis had a loculated fluid collection (p < .05). No statistically significant association was found between the presence or absence of perforation and free pelvic fluid, prominent periappendiceal fat, or an appendicolith. CONCLUSION: Our results indicate that sonography can be helpful in the diagnosis of perforating appendicitis. The best predictors of perforation are absence of the echogenic submucosal layer and the presence of a loculated fluid collection.

Acute Disease↗

A role of burst firings in encoding of spatiotemporally-varying stimulus.

To investigate a role of burst firings of neurons in encoding of spatiotemporally-varying stimulus, we focus on electrosensory system of a weakly electric fish. Weakly electric fish generates electric field around its body using electric organ discharge and can accurately detect the location of an object using the modulation of electric field induced by the object. We developed a model of fish body by which we numerically describe the spatiotemporal patterns of electric field around the fish body. We also made neural models of electroreceptor distributed on the fish body and of electrosensory lateral-line lobe (ELL) to investigate what kinds of information of electric field distorted by an object they detect. Here we show that the spatiotemporal features of electric field around the fish body are encoded by the timing of burst firings of ELL neurons. The information of object distance is extracted by the area of synchronous firings of neurons in a higher nucleus, torus semicircularis.

Action Potentials↗

The role of the saccade target object in the perception of a visually stable world.

Although the proximal stimulus shifts position on our retinae with each saccade, we perceive our world as stable and continuous. Most theories of visual stability implicitly assume a mechanism that spatially adjusts perceived locations associated with the retinal array by using, as a parameter, extra-retinal eye position information, a signal that encodes the size and direction of the saccade. The results from the experiment reported in this article challenge this idea. During a participant's saccade to a target object, one of the following was displaced: the entire scene, the target object, or the background behind the target object. Participants detected the displacement of the target object twice as frequently as the displacement of the entire background. The direction of displacement relative to the saccade also affected detectability. We use a new theory, the saccade target theory (McConkie & Currie, 1996), to interpret these results. This theory proposes that retinal (as opposed to extra-retinal) factors, primarily those concerning the saccade target object, are critical for the detection of intrasaccadic stimulus shifts.

Fixation, Ocular↗

Presumptive subarticular stress reactions of the knee: MRI detection and association with meniscal tear patterns.

OBJECTIVE: MRI detects subchondral marrow findings in painful knees which bear resemblance to spontaneous osteonecrosis of the knee (SONK). Gathering evidence suggests that the primary or predominant pathogenesis of these lesions is physical stress. This study analyzes the patient characteristics and meniscal pathology associated with these lesions-herein referred to as "presumptive subarticular stress related" (PSSR) lesions. DESIGN AND PATIENTS: All patients were scanned using a standardized imaging protocol. The criterion for a PSSR lesion was a subchondral marrow edema pattern encompassing a more focal, low-signal zone adjacent to or contiguous with the subchondral cortex. Patients were identified using an electronic database search of cases reported by one experienced musculoskeletal radiologist. RESULTS: Twenty-five PSSR lesions were identified among 1948 MRI evaluations of the knee. Twenty-one PSSR lesions occurred in the medial compartment, and four occurred in the lateral compartment. There was no sex predilection. Patients with PSSR lesions were older than other patients undergoing MRI evaluation (mean 66 years versus 52 years, P<0.001). Meniscal tears occurred more commonly in cases with PSSR lesions than in the group as a whole (76% versus 45%, P<0.001). Radial and posterior root tears were more common in knees with PSSR lesions than in other knees with meniscal tears (53% versus 26%, P<0.01). CONCLUSIONS: PSSR lesions are associated with meniscal tears and, more specifically, with meniscal tear patterns that dramatically increase contact forces across the knee joint. This observation supports the hypothesis that mechanical stress is important in the pathogenesis of these subarticular lesions that are detected by MRI.

Databases, Factual↗