Dynamic contrast-enhanced perfusion processing for neuroradiologists: model-dependent analysis may not be necessary for determining recurrent high-grade glioma versus treatment effect.

BACKGROUND AND PURPOSE: Dynamic contrast-enhanced perfusion MR imaging has proved useful in determining whether a contrast-enhancing lesion is secondary to recurrent glial tumor or is treatment-related. In this article, we explore the best method for dynamic contrast-enhanced data analysis. MATERIALS AND METHODS: We retrospectively reviewed 24 patients who met the following conditions: 1) had at least an initial treatment of a glioma, 2) underwent a half-dose contrast agent (0.05-mmol/kg) diagnostic-quality dynamic contrast-enhanced perfusion study for an enhancing lesion, and 3) had a diagnosis by pathology within 30 days of imaging. The dynamic contrast-enhanced data were processed by using model-dependent analysis (nordicICE) using a 2-compartment model and model-independent signal intensity with time. Multiple methods of determining the vascular input function and numerous perfusion parameters were tested in comparison with a pathologic diagnosis. RESULTS: The best accuracy (88%) with good correlation compared with pathology (P = .005) was obtained by using a novel, model-independent signal-intensity measurement derived from a brief integration beginning after the initial washout and by using the vascular input function from the superior sagittal sinus for normalization. Modeled parameters, such as mean endothelial transfer constant > 0.05 minutes(-1), correlated (P = .002) but did not reach a diagnostic accuracy equivalent to the model-independent parameter. CONCLUSIONS: A novel model-independent dynamic contrast-enhanced analysis method showed diagnostic equivalency to more complex model-dependent methods. Having a brief integration after the first pass of contrast may diminish the effects of partial volume macroscopic vessels and slow progressive enhancement characteristic of necrosis. The simple modeling is technique- and observer-dependent but is less time-consuming.

Clinical predictors of rectal lymphogranuloma venereum infection: results from a multicentre case-control study in the U.K.

OBJECTIVE: Since 2003, over 2000 cases of lymphogranuloma venereum (LGV) have been diagnosed in the U.K. in men who have sex with men (MSM). Most cases present with proctitis, but there are limited data on how to differentiate clinically between LGV and other pathology. We analysed the clinical presentations of rectal LGV in MSM to identify clinical characteristics predictive of LGV proctitis and produced a clinical prediction model. DESIGN: A prospective multicentre case-control study was conducted at six U.K. hospitals from 2008 to 2010. Cases of rectal LGV were compared with controls with rectal symptoms but without LGV. METHODS: Data from 98 LGV cases and 81 controls were collected from patients and clinicians using computer-assisted self-interviews and clinical report forms. Univariate and multivariate logistic regression was used to compare symptoms and signs. Clinical prediction models for LGV were compared using receiver operating curves. RESULTS: Tenesmus, constipation, anal discharge and weight loss were significantly more common in cases than controls. In multivariate analysis, tenesmus and constipation alone were suggestive of LGV (OR 2.98, 95% CI 0.99 to 8.98 and 2.87, 95% CI 1.01 to 8.15, respectively) and that tenesmus alone or in combination with constipation was a significant predictor of LGV (OR 6.97, 95% CI 2.71 to 17.92). The best clinical prediction was having one or more of tenesmus, constipation and exudate on proctoscopy, with a sensitivity of 77% and specificity of 65%. CONCLUSIONS: This study indicates that tenesmus alone or in combination with constipation makes a diagnosis of LGV in MSM presenting with rectal symptoms more likely.

Rapid increase in gonorrhoea and syphilis diagnoses in England in 2011.

There has been a rapid rise in the number of gonorrhoea and syphilis diagnoses in England during 2011, an increase of 25% and 10% respectively. Large increases of both gonorrhoea (61%) and syphilis (28%) were observed among men who have sex with men. Although these rises can partly be attributed to increased testing, ongoing high-levels of unsafe sexual behaviour probably contributed to the rise. The rise in gonorrhoea rates is worrying in an era of decreased susceptibility to treatments.

The prevalence of lymphogranuloma venereum infection in men who have sex with men: results of a multicentre case finding study.

OBJECTIVE: To determine the prevalence of lymphogranuloma venereum (LGV) and non-LGV associated serovars of urethral and rectal Chlamydia trachomatis (CT) infection in men who have sex with men (MSM). DESIGN: Multicentre cross-sectional survey. SETTING: Four genitourinary medicine clinics in the United Kingdom from 2006-7. SUBJECTS: 4825 urethral and 6778 rectal samples from consecutive MSM attending for sexual health screening. METHODS: Urethral swabs or urine and rectal swabs were tested for CT using standard nucleic acid amplification tests. Chlamydia-positive specimens were sent to the reference laboratory for serovar determination. MAIN OUTCOME: Positivity for both LGV and non-LGV associated CT serovars; proportion of cases that were symptomatic. RESULTS: The positivity (with 95% confidence intervals) in rectal samples was 6.06% (5.51% to 6.66%) for non-LGV CT and 0.90% (0.69% to 1.16%) for LGV; for urethral samples 3.21% (2.74% to 3.76%) for non-LGV CT and 0.04% (0.01% to 0.16%) for LGV. The majority of LGV was symptomatic (95% of rectal, one of two urethral cases); non-LGV chlamydia was mostly symptomatic in the urethra (68%) but not in the rectum (16%). CONCLUSIONS: Chlamydial infections are common in MSM attending for sexual health screening, and the majority are non-LGV associated serovars. We did not identify a large reservoir of asymptomatic LGV in the rectum or urethra. Testing for chlamydia from the rectum and urethra should be included for MSM requesting a sexual health screen, but serovar-typing is not indicated in the absence of symptoms. We have yet to identify the source of most cases of LGV in the UK.

A trial of the validity of genital smears and cultures with gonococcal vaccine provocation in diagnosing genital gonorrhoea in women.

In Russia the diagnosis of gonorrhoea in women relied on microscopy, justified by the hypothesis that sensitivity increases using 'provocation' techniques. The aim was to test the value of Gonovaccine as provocation in women who would have received it normally. Cervical specimens from 204 women were tested by culture and a ligase chain reaction (LCR) assay before the women were randomized to receive provocation or not. Further cervical specimens were obtained 24, 48 and 72 hours later for microscopy, culture and LCR tests. In both provocation and non-provocation arms, 24 women were positive for gonorrhoea by the LCR assay. Test-by-test, sensitivity of microscopy was 30% in the provocation arm and 13% in the control arm (P = 0.0407, Fisher's exact test). Patient-by-patient, sensitivity of microscopy was 50% in the provocation arm, but only 25% in the control arm (P = 0.0675, Fisher's exact test). The cost per case was greater ($214) using provocation with microscopy than culture and microscopy at the first visit ($150). Thus, although Gonovaccine provocation doubled the sensitivity of microscopy in detecting gonococci, the internationally recommended protocol of microscopy and culture at first visit should be adopted as routine practice in Russia. The findings raise questions about the pathogenesis and natural history of gonorrhoea.

Performance of direct fluorescent antibody tests for routine diagnosis of Chlamydia trachomatis in Russian sexually transmitted disease clinics.

SUMMARY: Testing for Chlamydia trachomatis in Russia is usually done by microscopic examination of genital smears stained with fluorescent antibody provided in locally produced kits. The aim was to assess the sensitivity and specificity of such direct fluorescent antibody (DFA) tests compared with a nucleic acid amplification test (NAAT) (ligase chain reaction) to detect C. trachomatis in 171 cervical smears and 201 urethral smears from men. The patients were at high risk of chlamydial infection and had been recruited at three sexually transmitted disease clinics in Moscow. Among women, DFA test sensitivity was 6% (95% CI 0-14) and the specificity was 92% (95% CI 88-97). Among men, the sensitivity was 9% (95% CI 2-16) and the specificity was 90% (95% CI 83-94). Poor DFA test performance was probably due to poor antibody quality and such tests are not adequate for routine examination of populations with either low or high chlamydial prevalence. As there may remain a place for DFA testing where few patients are seen, the Russian Ministry of Health should enforce registration of diagnostic tests, and Russian manufacturers should seek ways of improving DFA test performance. However, the mainstay of testing should depend on NAATs.

How is the high vaginal swab used to investigate vaginal discharge in primary care and how do GPs' expectations of the test match the tests performed by their microbiology services?

OBJECTIVES: To describe the management of vaginal discharge in general practice, with particular regard to the use of the high vaginal swab (HVS), and to compare GPs' expectations of this test with the processing and reporting undertaken by different laboratories. METHODS: A postal questionnaire survey of 2146 GPs in the North Thames area and postal questionnaire study of the 22 laboratories serving the same GPs were carried out. GPs were asked how they would manage a young woman with vaginal discharge and what information they would like on an HVS report. Laboratories were asked how they would process and report on the HVS sample from the same patient. RESULTS: Response rate was 26%. 72% of GPs would take an HVS and 62% would refer on to a genitourinary medicine (GUM) clinic. 45% would offer empirical therapy and 47% of these would treat for candida initially. 75% of GPs routinely request "M,C&S" on HVS samples but 55% only want to be informed about specific pathogens. Routine processing of HVS samples varies widely between laboratories and 86% only report specific pathogens. 78% of GPs would like to be offered a suggested diagnosis on HVS reports, and 74% would like a suggested treatment. 43% of laboratories ever provide a diagnosis, and 14% provide a suggested treatment. CONCLUSIONS: GPs frequently manage vaginal discharge and most of them utilise the HVS. GPs' expectations of the test are not well matched to laboratory processing or reporting of the samples.

Validation of a simplified grading of Gram stained vaginal smears for use in genitourinary medicine clinics.

OBJECTIVES: To validate a simplified grading scheme for Gram stained smears of vaginal fluid for the diagnosis of bacterial vaginosis (BV) against the accepted "gold" standard of Amsel's composite criteria. METHODS: Women attending genitourinary medicine (GUM) clinics, as part of a multicentre study, were diagnosed as having BV if three or more of the following criteria were present; homogeneous discharge, elevated vaginal pH, production of amines, and presence of "clue" cells. Women with less than three of the criteria were considered as normal. Simultaneously, smears were made of vaginal fluid and Gram stained and then assessed qualitatively as normal (grade I), intermediate (grade II), or consistent with BV (grade III). Two new grades were used, grade 0, epithelial cells only with no bacteria, and grade IV, Gram positive cocci only. RESULTS: BV was diagnosed in 83/162 patient visits using the composite criteria, the remainder being regarded as normal. The majority of patients with BV had a smear assessed as grade III (80/83, 96%) and the majority of normal women had a smear assessed as grade I (normal, 48/79, 61%), giving a high sensitivity (97.5%), specificity (96%), and predictive value for a positive (94.1%) and negative (96%) test, kappa index = 0.91. Smears assessed as grade II were found predominantly (12/13) among patients diagnosed as normal, with less than three of the composite criteria. Grades 0 and IV were both only found among normal women. CONCLUSION: This simplified assessment of Gram stained smears can be used as an alternative to Amsel's criteria and is more applicable for use in busy GUM clinics.

An international study of the interobserver variation between interpretations of vaginal smear criteria of bacterial vaginosis.

An international workshop on vaginal smear-based diagnosis of bacterial vaginosis was organized where 13 investigators scoring 258 slides with smears from vaginal fluid. Interobserver reproducibility of interpretations of Nugent scores, Hay/Ison scores and wet smear scores for the diagnosis of bacterial vaginosis was shown to be high. Detailed analysis of individual scoring results however indicated that basic standards of quality control to ensure robust individual readings of slides must be adhered to.

Cellular immune responses to Neisseria meningitidis in children.

There is an urgent need for effective vaccines against serogroup B Neisseria meningitidis. Current experimental vaccines based on the outer membrane proteins (OMPs) of this organism provide a measure of protection in older children but have been ineffective in infants. We postulated that the inability of OMP vaccines to protect infants might be due to age-dependent defects in cellular immunity. We measured proliferation and in vitro production of gamma interferon (IFN-gamma), tumor necrosis factor alpha, and interleukin-10 (IL-10) in response to meningococcal antigens by peripheral blood mononuclear cells (PBMCs) from children convalescing from meningococcal disease and from controls. After meningococcal infection, the balance of cytokine production by PBMCs from the youngest children was skewed towards a TH1 response (low IL-10/IFN-gamma ratio), while older children produced more TH2 cytokine (higher IL-10/IFN-gamma ratio). There was a trend to higher proliferative responses by PBMCs from older children. These responses were not influenced by the presence or subtype of class 1 (PorA) OMP or by the presence of class 2/3 (PorB) or class 4 OMP. Even young infants might be expected to develop adequate cellular immune responses to serogroup B N. meningitidis vaccines if a vaccine preparation can be formulated to mimic the immune stimulus of invasive disease, which may include stimulation of TH2 cytokine production.

A comparison of the use of Papanicolaou-stained cervical cytological smears with Gram-stained vaginal smears for the diagnosis of bacterial vaginosis in early pregnancy.

Our objective is to compare the efficacy of using Papanicolaou (PAP)-stained cervical cytology smears with a standardized method of interpreting Gram-stained vaginal smears for the diagnosis of bacterial vaginosis (BV) in pregnancy. High vaginal smears were Gram-stained and examined by a single observer to characterize 3 grades of vaginal flora and diagnose BV. Cervical smears were PAP-stained and examined for characteristic patterns of vaginal flora including evidence of BV by either a number of cytotechnicians or a single cytopathologist. The results of the 2 methods were compared. Seven hundred and forty-seven women attending an antenatal clinic in a district general hospital who consented to have a smear of vaginal secretions and cervical cytology in early pregnancy. The main outcome measure is the diagnosis of BV by different methods in a pregnant population. Compared with the Gram-stain method for the diagnosis of BV, there was good agreement between PAP-stain interpretation by a single observer but the agreement was not as good with PAP-stain interpretation by multiple cytotechnicians. When the grades were consolidated to normal (grade I) and abnormal flora (grades II and III), compared to Gram-stained smears, PAP cytology undertaken by several cytotechnicians had a sensitivity of 80.7% and a specificity of 90.7%. The sensitivity and specificity increased to 87% and 97%, respectively, when the PAP-stained smears were read by a single cytopathologist. Using kappa scores, only those readings made by a single cytopathologist were reliable. The setting in a cytopathology laboratory comprises multiple cytotechnicians, so that PAP-stain analysis of vaginal smears for the diagnosis of BV is likely to provide results which are less reliable than those obtained by Gram staining. The latter should be the first choice and every effort should be made to set up this service.

Association of bacterial vaginosis with a history of second trimester miscarriage.

The aim of this study was to determine whether bacterial vaginosis (BV) is associated with a history of recurrent pregnancy loss. A total of 500 consecutive patients attending the Recurrent Miscarriage Clinic were screened for the presence of BV. In women who had had at least one late miscarriage BV was found twice as commonly (27/130; 21%) as in women who had had only early losses (31/370; 8%) (P < 0.001). The difference was even larger (26 versus 8%) if women who had had term pregnancies were excluded. Moreover, BV was found three times more commonly in Afro-Caribbean women [17 (29%) of 58] than in Caucasian women [36 (9%) of 379] and, in both groups of women, BV was diagnosed at least twice as frequently in those with a history of at least one late miscarriage than in those who had experienced first trimester pregnancy losses only (P < 0. 001). The condition occurred twice as often among smokers than non-smokers and, in both groups, it was at least twice as common in women with a history of at least one late miscarriage as in those who had had early pregnancy losses only (P < 0.001). However, the relationship between BV and smoking was independent of ethnic origin. Women who douched with chloroxylenol were mostly Afro-Caribbean and had BV more than twice as often as women who did not douche.

Whole blood model of meningococcal bacteraemia--a method for exploring host-bacterial interactions.

An ex vivo whole blood model of meningococcal bacteraemia was developed to examine the total bactericidal activity of blood. Using a single defined donor and strains belonging to serogroups A, B and C and an unencapsulated strain, we demonstrated that the bactericidal mechanisms operating in whole blood varied with anticoagulant, serogroup and bacterial growth conditions. The choice of anticoagulant had a major effect on the survival of the serogroup A strain with 94% (SEM 7.6) survival in citrated blood compared to 19.7% (SEM 19.6) survival in heparinised blood after 60 min incubation. The serogroup C strain showed enhanced survival when grown in liquid medium compared to growth on solid medium (73.5%, SEM 7.5, and 8.2%, SEM 3.1, respectively, in citrated blood after 60 min). The pattern of survival of serogroup B and the unencapsulated strain were largely unaffected by these variables. Comparison with cell free conditions allowed the contribution of cellular components in meningococcal killing to be determined. Secreted levels of tumour necrosis factor and neutrophil elastase secreted during whole blood assays did not correlate with bacterial growth or viability indicating a lack of relationship between killing and activation of phagocytes.