The gene for tubular basement membrane (Tbm) antigen in the rat has been mapped relative to other markers in the first linkage group, and a polymorphic locus for a submaxillary gland protease, Tamase-1, has been identified. The hair-loss mutation fuzzy has also been mapped and occupies a position which is similar to that of the frizzy gene in the mouse. There are now at least five, and possibly six, genetic loci distributed over more than 30 centimorgans in the first linkage group of the rat which map in positions of approximate homology on the seventh chromosome of the mouse.

BACKGROUND

Spouses of patients with cancer are at risk for stress-related disorders and may experience a reduction in immune function. Therapeutic back massage (TBM) has been shown to enhance relaxation and thus, may reduce stress associated with caring for an ill partner.

OBJECTIVE

To determine if TBM's influences on psychosocial, physiologic, and immune function variables in spouses of patients with cancer, and explore the relationships between psychosocial variables and immune function in spouses of patients with cancer.

METHODS

This group experimental design measured the effects of a 20-minute TBM at three time points (preintervention, immediately postintervention, 20 minutes postintervention) on spouses of patients with cancer (N= 42) randomly assigned to either the experimental or control group. The major dependent variables including natural killer cell activity (NKCA), heart rate, systolic and diastolic blood pressure, mood, and perceived stress were measured at the three time points to examine the effects of TBM. Data collected on measures of mood and perceived stress were correlated with NKCA to examine their relationships. Prior to hypotheses testing, data collected on measures of depressive mood, loneliness, marital disruption, and health practices were also correlated with NKCA to ascertain any possible confounding variables.

RESULTS

Two-way repeated measures analysis of variance tests determined the effects of TBM over the two postintervention time points and resulted in significant group x time interactions on mood (F [2, 40]= 14.61, p=.0005) and perceived stress (F [2, 40]= 28.66, p=.001). Significant inverse relationships were found between mood and NKCA (r= -.41, p=.009, N= 42) and perceived stress and NKCA (r= -.37, p=.017, N= 42).

CONCLUSIONS

Findings suggest that TBM may enhance mood and reduce perceived stress in this population. Insight was gained into the psycho-immunologic relationships studied.

OBJECTIVE

Because we had previously observed geometric changes of frontal lobe association pathways in children with ASD, in the present study we analyzed the curvature of these white matter pathways by using an objective TBM analysis.

METHODS

Diffusion tensor imaging was performed in 32 children with ASD and 14 children with typical development. Curvature, FA, AD, and RD of bilateral AF, UF, and gCC were investigated by using the TBM group analysis assessed by P(FDR) for multiple comparisons.

RESULTS

Significantly higher curvatures were found in children with ASD, especially at the parietotemporal junction for AF (left, P(FDR) < .001; right, P(FDR) < .01), at the frontotemporal junction for UF (left, P(FDR) < .005; right, P(FDR) < .03), and at the midline of the gCC (P(FDR) < .0001). RD was significantly higher in children with ASD at the same bending regions of AF (left, P(FDR) < .03, right, P(FDR) < .02), UF (left, P(FDR) < .04), and gCC (P(FDR) < .01).

CONCLUSIONS

Higher curvature and curvature-dependent RD changes in children with ASD may be the result of higher attenuation of thinner axons in these frontal lobe tracts.

We have studied the dogfish erythrocyte cytoskeletal system, which consists of a marginal band of microtubules (MB) and trans-marginal band material (TBM). The TBM appeared in whole mounts as a rough irregular network and in thin sections as a surface-delimiting layer completely enclosing nucleus and MB. In cells incubated at 0 degrees C for 30 min or more, the MB disappeared but the TBM remained. MB reassembly occurred with rewarming, and was inhibited by colchicine. Flattened elliptical erythrocyte morphology was retained even when MBs were absent. Total solubilization of MB and TBM at low pH, or dissolution of whole anucleate cytoskeletons, yielded components comigrating with actin, spectrin, and tubulin standards during gel electrophoresis. Mass-isolated MBs, exhibiting ribbonlike construction apparently maintained by cross-bridges, contained four polypeptides in the tubulin region of the gel. Only these four bands were noticeably increased in the soluble phase obtained from cells with 0 degrees C-disassembled MBs. The best isolated MB preparations contained tubulin but no components comigrating with high molecular weight microtubule-associated proteins, spectrin, or actin. Actin and spectrin therefore appear to be major TBM constituents, with tubulin localized in the MB. The results are interpreted in terms of an actin- and spectrin-containing subsurface cytoskeletal layer (TBM), related to that of mammalian erythrocytes, which maintains cell shape in the absence of MBs. Observations on abnormal pointed erythrocytes containing similarly pointed MBs indicate further that the MB can deform the TBM from within so as to alter cell shape. MBs may function in this manner during normal cellular morphogenesis and during blood flow in vivo.

Intracranial pressure (ICP) was monitored in 218 consecutive children with hydrocephalus secondary to tuberculous meningitis (TBM). All children underwent cranial computerized tomographic (CT) scanning and continuous lumbar cerebrospinal (CSF) pressure monitoring on admission. Noncommunicating hydrocephalus (37 children), as determined by air encephalography, was treated by ventriculoperitoneal (VP) shunting and communicating hydrocephalus (181 children), by means of daily acetazolamide and frusemide. Response of ICP to treatment in the group with communicating hydrocephalus was assessed by means of repeated CSF pressure monitoring and CT scanning. One hundred and eighty-five of the 218 patients survived the 1st month of treatment. The aim of this study was the retrospective determination of (1) the relationship between ICP measurements and CT findings on admission and (2) the characteristics of the ICP recording which correlated best with the CT criteria of compensated hydrocephalus after the 1st month of treatment. No relationship was found between the level of baseline CSF pressure and the degree of hydrocephalus, as demonstrated by CT scanning, on admission. Seventy-five per cent of the patients with communicating hydrocephalus that survived the 1st month of treatment complied with the CT criteria for compensated hydrocephalus. All these patients had a baseline CSF pressure below 15 mmHg and absence of high-amplitude B waves on the pressure recording done at the end of the 1st month. In this study repeated lumbar CSF pressure monitoring proved to be an effective instrument to assess the response of communicating tuberculous hydrocephalus to medical treatment and also accurately predicted the timing of compensation of the hydrocephalus.

The purpose of this study was to compare power outputs, and blood concentrations of lipid hydroperoxides (LH), malondialdehyde (MDA), creatine kinase (CK), myoglobin (Mb) and lactate ([La-]B) following 30 s of maximal cycle ergometry when resistive forces were derived from total-body mass (TBM) or fat-free mass (FFM). Alpha-tocopherol (AT), retinol (R) and uric acid (UA) concentrations were also measured to qualify the activity of antioxidants. Cardiac troponin levels were determined to exclude myocardial damage and to verify that any CK was predominantly derived from skeletal muscle. Differences (P<0.05) in peak power output, pedal velocity and resistive forces were observed when the TBM and FFM protocols were compared [953 (114) W vs 1,020 (134) W; 134 (8) rpm vs 141 (7) rpm; 6 (1) kg vs 5 (1) kg respectively). LH and MDA concentrations increased immediately post-exercise during the TBM protocol only (P<0.05) and were greater when compared to FFM (P<0.05). LH and MDA values decreased 24 h post-exercise. Increases in CK concentrations were recorded immediately post-exercise for both the TBM and FFM protocols with greater concentrations recorded for TBM (P<0.05). Decreases were observed 24 h post-exercise. Mb concentrations were greater immediately post-exercise for the TBM protocol and were greater than those recorded for FFM (P<0.05). Values decreased 24 h later (P<0.05). AT and UA concentrations decreased immediately post-exercise for both protocols (P<0.05) and increased 24 h later (P<0.05). There were no changes observed in R concentrations at any of the blood sampling stages. [La-]B increased (P<0.05) immediately post-exercise for both protocols, and decreased 24 h later (P<0.05). The results of the study suggest that greater power outputs are obtainable with significantly less oxidative stress and muscle disruption when resistive forces reflect FFM mass as opposed to TBM.

Tracheobronchomegaly (TBM) is a rare disorder of uncertain aetiology, characterized by marked dilatation of the trachea and main bronchi, bronchiectasis and recurrent lower respiratory tract infections. Two patients with TBM are presented. In one case, a marked decrease of elastic and smooth muscle tissue was present in the bronchial biopsy specimens, obtained by rigid bronchoscopy. The airways of the second patient were visualized using computed tomography. The dimensions of the airways of our patients are compared with the normal values supplied in the literature.

OBJECTIVE

Early diagnosis and treatment of tuberculous meningitis (TBM) saves lives, but current laboratory diagnostic tests lack sensitivity and the best treatment regimens are uncertain. This article reviews the advances towards better TBM diagnosis and treatments made over the last 2 years.

RESULTS

A modified Ziehl-Neelsen stain, interferon-gamma release assays and Mycobacterium tuberculosis antigen detection assays have all shown promise as new TBM diagnostic tests. HIV-associated TBM carries an especially grave prognosis and there are new data describing the optimal timing of antiretroviral treatment initiation and the clinical predictors of TBM immune reconstitution inflammatory syndrome. The pharmacokinetic and pharmacodynamic properties of different fluoroquinolones for TBM treatment have been compared, and there are intriguing new data to suggest higher doses of rifampicin given intravenously may improve the survival. Finally, there are preliminary data to suggest that the beneficial effect of adjunctive corticosteroids on TBM survival may be augmented by aspirin and predicted by a polymorphism in a gene responsible for eicosanoid synthesis.

CONCLUSIONS

Much remains to be done to improve the outcome from TBM. There have been important advances in the treatment, which may influence treatment guidelines in the near future, but there remains an urgent need for better diagnostic tests.

METHODS

Short course chemotherapy for tuberculous meningitis (TBM) is advocated by several groups, but relatively few children have been so treated and followed up.

METHODS

A prospective, observational study of isoniazid (INH), rifampicin (RMP) and ethionamide (ETH) in a dosage of 20 mg/kg, and pyrazinamide (PZA) 40 mg/kg, all given once daily in hospital for 6 months. Surviving children were followed up for a year after discharge.

RESULTS

Ninety five children, 39 (41%) at stage III, 52 (55%) at stage II and 4 (4%) at stage I TBM were studied. Ten (26%) at stage III and 3 (6%) at stage II died before completion of therapy. Five surviving children (6%) moved on discharge and were untraceable; seven children (9%) were lost during follow up and three were inadvertently restarted on antituberculosis therapy. Two children with severe stage III disease died after discharge. One child experienced a probable disease recrudescence 1 month after discharge. Eighteen children (20%) developed a mildly elevated serum bilirubin concentration during the first month of treatment. In five of these children INH, RMP, ETH and PZA were stopped and streptomycin (SM) and ethambutol substituted. In all cases the original treatment was restarted without incident. One child developed overt jaundice after 5 months of treatment due to hepatitis A infection.

CONCLUSIONS

Our experience suggests that young children with TBM can be safely treated for 6 months with high doses of antituberculosis agents without overt hepatotoxicity and with a low risk of relapse.

The in vivo significance of suppressor macrophages for antitumor immunity was investigated in a syngeneic tumor system. The presence of suppressor macrophages in the spleens of X5563 C3H/HeN tumor-bearing mice (TBM) was directly shown in vitro. Thus the addition of splenic macrophages of TBM suppressed the in vitro secondary induction of both tumor-specific cytotoxic T-cells and effector cells of the delayed-type hypersensitivity reaction. Splenic macrophages of TBM exerted suppression on tumor-specific T-cell-mediated cytotoxicity in the effector phase as well. Prostaglandin production was found to be one of the major mechanisms involved in macrophage-induced suppression. In vivo treatment of TBM with carrageenan and/or indomethacin retarded tumor growth and in parallel augmented cell-mediated cytotoxicity against X5563 cells, probably by affecting suppressor macrophages in vivo. The suppressive effect of splenic macrophages from TBM was clearly demonstrated in a tumor-neutralization test indicating that suppressor macrophages were able to exert their function in vivo as well as in vitro. All these results suggested that suppressor macrophages had in vivo significance for the suppression of the immunosurveillance of the hosts.

A new combined methodology consisting of direct observation and two types of interviews (internal and external interviews) was evaluated for use in exposure risk assessment in schistosomiasis. Specific objectives were to determine its usefulness in achieving equitable coverage of gendered exposure risk and its efficiency in identifying water contact behavior in a rural area in Brazil with different settlement patterns, land use and domestic water supplies. Of the 2476 water contacts recorded, 1223 (49.4%) were identified by direct observation, 946 (38.2%) by internal interviews and 307 (12.4%) by external interviews. Significantly longer mean durations of contacts were recorded for females and greater mean percentage of body surface exposed for males (P<0.01), reflecting differences in gendered water contact activities. Direct observation identified slightly more male contacts, external interviews significantly more male contacts (P<0.006), and internal interviews moderately more female contacts. The three methods recorded mean numbers of contacts and mean TBM (total body minutes) per person, declining with age. Significant differences were found between the three methods in regard to frequency and/or intensity of washing clothes, fetching water, washing utensils, washing multiple parts of the body, and bathing. The three methods also recorded differentially frequencies and exposure intensities in the three study communities, among different age groups, by gender and for individual study members. These activity-, locality-, age/gender- and person-specific patterns reflect the relative efficiency and complementarity of the three methods in settlements with different land use, access to streams and water supplies.

In recent years higher incidence rates of tuberculosis (TB) have been reported from the Western Cape than from other health regions of South Africa. In contrast to the various pulmonary forms of tuberculosis, tuberculous meningitis (TBM) always requires hospital admission, and can thus be used as an indicator of the extent of the infection in a community, as well as providing a measure of the effectiveness of primary and secondary preventive measures. In the present study an attempt was made to identify all cases of tuberculous meningitis aged 14 years and younger which occurred in the region, by checking notifications and the records of all hospitals, and verifying diagnosis against set criteria. Rates for the entire period were calculated according to updated census data. There was a total of 689 confirmed cases, of which only 55% had been notified. Of the 238 cases confirmed in the 3-years period, 1985-1987, 25.2% were under 1 year, 51.7% under 2 years, and 79.8% under 5 years of age. Age-specific incidence per 100,000 children were respectively 31.5 (0-1 years), 17.1 (1-4 years), 4.8 (5-9 years), and 0.7 (10-14 years). Rates in rural areas were far higher than in metropolitan regions. Utilizing tuberculin test data and total notifications, the following risks could be calculated for 'Coloured' children (of mixed race) aged 0-4 years: 2-3% annual risk of infection; 15.7% risk of TB in infected population; 0.5% risk of TBM in infected population; 0.9% risk of TB in children aged 5-14 years; 0.01% risk of TBM in children aged 5-14 years.

This community-based study analyzed 54 patients with definite or probable tuberculous meningitis (TBM) in New Mexico from 1970 through 1990. Patients ranged in age from 4 months to 86 years. The highest age-specific incidence occurred in the elderly, but 22% of patients were less than 10 years old. Native American patients were overrepresented. Patients were as likely to live in small towns as in large urban cities. Symptoms were present for a median of 13 days before admission. The majority of patients had fevers, headache, stiff neck, and mental changes, such as confusion or lethargy. No patient was admitted comatose. Focal neurologic signs were present in 33%. Laboratory testing found hyponatremia in 79%, pulmonary infiltrates on chest x-ray in 40%, ventricular dilatation on CT or MRI in 52%, and tuberculomas in 16%. PPD skin tests were positive in 64%. CSF cultures grew Mycobacterium tuberculosis in 50%, but colony counts were always lower than 10(2)/ml. As a consequence, acid-fast stains of CSF sediment were reported as positive in only 4%. Six patients were not diagnosed during the hospitalization and died of complications. Twenty-three percent of patients who were appropriately treated also died of complications during the initial hospitalization. Tuberculous meningitis continues to be an important disease in small communities, and affects all ages and ethnic and socioeconomic backgrounds.

Forkhead box transcription factor M1 (FOXM1) is a proliferation-associated transcription factor involved in tumorigenesis through transcriptional regulation of its target genes in various cells, including dendritic cells (DCs). Although previous work has shown that FOXM1 enhances DC maturation in response to house dust mite allergens, it is not known whether FOXM1 affects DC maturation in the context of tumor-specific immunity. In this study, we examined the central role of FOXM1 in regulating bone marrow-derived dendritic cell (BMDC) maturation phenotypes and function in pancreatic cancer and colon cancer. FOXM1 retarded maturation phenotypes of BMDCs, inhibited promotion of T-cell proliferation, and decreased interleukin-12 (IL-12) p70 in tumor-bearing mice (TBM). Notably, FOXM1 expression was epigenetically regulated by dimethylation on H3 lysine 79 (H3K79me2), a modification present in both tumor cells and BMDCs. Increased H3K79me2 enrichment was observed at the FOXM1 promoter in both BMDCs from TBM, and in BMDCs from wild-type mice cultured with tumor-conditioned medium that mimics the tumor microenvironment (TME). Furthermore, inhibition of the H3K79 methyltransferase DOT1L not only decreased enrichment of H3K79me2, but also downregulated expression of FOXM1 and partially reversed its immunosuppressive effects on BMDCs. Furthermore, we found that FOXM1 upregulated transcription of Wnt family number 5A (Wnt5a) in BMDCs in vitro; we also observed that exogenous Wnt5a expression abrogated BMDC maturation phenotypes by inhibiting FOXM1 and H3K79me2 modification. Therefore, our results reveal that upregulation of FOXM1 by H3K79me2 in pancreatic cancer and colon cancer significantly inhibits maturation phenotypes and function of BMDCs through the Wnt5a signaling pathway, and thus provide novel insights into FOXM1-based antitumor immunotherapy.

OBJECTIVE

Tuberculous meningitis (TBM) is the severest form of tuberculosis, but current diagnostic tests are insensitive. Recent reports suggest simple modifications to conventional cerebrospinal fluid (CSF) Ziehl-Neelsen (ZN) staining may greatly improve sensitivity. We sought to define the performance of modified and conventional ZN stain for TBM diagnosis.

METHODS

In hospitals in Vietnam, South Africa and Indonesia we conducted a prospective study of modified ZN with or without cytospin, conventional ZN smear, GeneXpert, and culture on CSF in adults with suspected TBM.

RESULTS

A total of 618 individuals were enrolled across 3 sites. Compared with the TBM clinical diagnostic gold standard for research (definite probable or possible TBM), sensitivity of conventional ZN and modified ZN with cytospin were 33.9% and 34.5% respectively (p = 1.0 for the difference between tests), compared with culture 31.8% and Xpert 25.1%. Using culture as a reference, sensitivities of conventional ZN, modified ZN with cytospin, and Xpert were 66.4%, 67.5%, and 72.3%, respectively. Higher CSF volume and lactate, and lower CSF:blood glucose ratio were independently associated with microbiologically confirmed TBM.

CONCLUSIONS

Modified ZN stain does not improve diagnosis of TBM. Currently available tests are insensitive, but testing large CSF volumes improves performance. New diagnostic tests for TBM are urgently required.

The α-hemolysin (αHL) protein nanopore has been investigated previously as a base detector for the strand sequencing of DNA and RNA. Recent findings have suggested that shorter pores might provide improved base discrimination. New work has also shown that truncated-barrel mutants (TBM) of αHL form functional pores in lipid bilayers. Therefore, we tested TBM pores for the ability to recognize bases in DNA strands immobilized within them. In the case of TBMΔ6, in which the barrel is shortened by ∼16 Å, one of the three recognition sites found in the wild-type pore, R1, was almost eliminated. With further mutagenesis (Met113 → Gly), R1 was completely removed, demonstrating that TBM pores can mediate sharpened recognition. Remarkably, a second mutant of TBMΔ6 (Met113 → Phe) was able to bind the positively charged β-cyclodextrin, am7βCD, unusually tightly, permitting the continuous recognition of individual nucleoside monophosphates, which would be required for exonuclease sequencing mediated by nanopore base identification.

Tracheobronchomalacia (TBM) results from weakness of the airway walls and/or supporting cartilage and affects both adult and pediatric populations. Diagnosing TBM is challenging because symptoms are nonspecific and overlap with those of other chronic respiratory disorders. Recent advances in multidetector computed tomography have facilitated the noninvasive diagnosis of TBM, and concurrent advances in management have improved clinical outcomes and created a need for greater awareness of the posttreatment appearance of the airways. This review discusses the physiology, histopathology, epidemiology, and clinical features of TBM; it also describes current methods of diagnosis, available therapies, and postoperative imaging evaluation.

OBJECTIVE

To study the diagnostic test characteristics of computed tomography (CT scan) in differentiating tuberculous (TBM) and pyogenic (PM) meningitis.

METHODS

Prospective diagnostic test evaluation.

METHODS

Teaching hospital.

METHODS

Children beyond 1 month of age admitted with meningitis were enrolled prospectively and CT scan done. Results of CT scan were compared with predefined gold standards for the diagnosis of either TBM or PM.

RESULTS

CT scan was performed in 154 patients with meningitis. Of these 94 were TBM, 52 had PM and 8 were indeterminate and excluded from analysis. Basal enhancement, ventriculomegaly, tuberculoma and infarction were all significantly more common in the TBM group, while subdural collections were seen more in the PM group. The highest sensitivity (89.2%) and specificity (100%) for diagnosis of TBM were found for basal enhancement or tuberculoma or both.

CONCLUSIONS

CT scan can be used to effectively distinguish TBM and PM.

We present a model to calculate particle size distributions (PSDs) of colloidal ZnO nanoparticles from their absorbance spectra. Using literature values for the optical properties of bulk ZnO and correlating the measurement wavelengths in the UV-visible regime with distinct particle sizes by a tight binding model (TBM), an algorithm deconvolutes the absorbance spectra into contributions from size fractions. We find an excellent agreement between size distributions determined from TEM images and the calculated PSDs. For further validation, bimodal PSDs have been investigated and an approach to determine not only particle size but also solid concentration is introduced. We will show the applicability of our model by the determination of temperature-dependent ripening rates, which enables the calculation of solubilities, surface tensions, and the activation enthalpy of ripening. In principle, our methodology is applicable to different semiconductor nanoparticles in various solvents as long as their bulk properties are known and scattering is negligible.

OBJECTIVE

This study aimed to evaluate epidemiological, clinical, laboratory, and neuroimaging features of 160 adult patients with tuberculous meningitis (TBM) according to "Thwaites' diagnostic index."

METHODS

The subjects of this retrospective study are the patients with TBM who were followed up between years 1998 and 2009 in a tertiary referral hospital. Diagnosis of TBM was based on clinical, laboratory, and neuroimaging signs and Thwaites' diagnostic index.

RESULTS

Mycobacterium tuberculosis was isolated from CSF in 59 of 148 patients. Seventeen percent of the patients died, 71% recovered completely, and 13% recovered with neurological sequel at the end of the sixth month.

CONCLUSIONS

Despite new developments in laboratory or neuroimaging techniques, the diagnosis of TBM is still based on clinical features with the help of laboratory. Early diagnosis by suspecting TBM may prevent therapy delay and may result in decrease in the mortality and morbidity.

OBJECTIVE

There are few studies on the long-term outcome of tuberculous meningitis (TBM) employing multivariate analysis. The present study was undertaken to evaluate the outcome predictors of TBM at 6 and 12 months.

METHODS

Those patients with TBM who could be sequentially followed up for 6 and 12 months were included in this prospective, hospital-based study. The outcome was defined at 6 and 12 months by Barthel Index (BI) score into complete (BI = 20), partial (BI = 12-19) and poor (BI<12). Death was included in the 'poor recovery' group for statistical analysis. A number of clinical, laboratory and radiological parameters were evaluated by multiple regression analysis.

RESULTS

Fifty-eight patients with TBM aged between 1 and 64 years (mean 25.6 years), 18 of whom were females and 17 children below 12 years, were included in the study. Fifty-eight patients were followed up for 6 months and 56 for 12 months. At 6 months' follow-up 37 patients had complete recovery, three partial, six poor and 12 had died. At 12 months, 40 patients had complete recovery, one partial and three poor. The best set of parameters predicting outcome at 6 and 12 months included stage of TBM, Glasgow coma scale (GCS) and brain infarction.

CONCLUSIONS

This study highlights the importance of stage of meningitis, GCS and infarction in predicting the long term outcome of tuberculous meningitis.

The goal of this work was to assess statistical power to detect treatment effects in Alzheimer's disease (AD) clinical trials using magnetic resonance imaging (MRI)-derived brain biomarkers. We used unbiased tensor-based morphometry (TBM) to analyze n = 5,738 scans, from Alzheimer's Disease Neuroimaging Initiative 2 participants scanned with both accelerated and nonaccelerated T1-weighted MRI at 3T. The study cohort included 198 healthy controls, 111 participants with significant memory complaint, 182 with early mild cognitive impairment (EMCI) and 177 late mild cognitive impairment (LMCI), and 155 AD patients, scanned at screening and 3, 6, 12, and 24 months. The statistical power to track brain change in TBM-based imaging biomarkers depends on the interscan interval, disease stage, and methods used to extract numerical summaries. To achieve reasonable sample size estimates for potential clinical trials, the minimal scan interval was 6 months for LMCI and AD and 12 months for EMCI. TBM-based imaging biomarkers were not sensitive to MRI scan acceleration, which gave results comparable with nonaccelerated sequences. ApoE status and baseline amyloid-beta positron emission tomography data improved statistical power. Among healthy, EMCI, and LMCI participants, sample size requirements were significantly lower in the amyloid+/ApoE4+ group than for the amyloid-/ApoE4- group. ApoE4 strongly predicted atrophy rates across brain regions most affected by AD, but the remaining 9 of the top 10 AD risk genes offered no added predictive value in this cohort.

BACKGROUND

Tuberculous meningitis (TBM) is one of the common clinical manifestations of extra-pulmonary tuberculosis. It is difficult to diagnose due to a lack of rapid, sensitive, and specific tests. Newer methods, which are easy and reliable, are required to diagnose TBM at an early stage. Thus our aim was to evaluate the polymerase chain reaction (PCR) technique, using primers directed against the IS6110 gene, for the detection of Mycobacterium tuberculosis in the CSF, for the diagnosis of TBM patients.

METHODS

An in-house IS6110 PCR method using a specific pair of primers designed to amplify the insertion sequence, IS6110, in the M. tuberculosis genome was used to analyze CSF. A total of 80 CSF samples from different groups of patients were studied (confirmed TBM n = 35, clinically suspected TBM n = 16, non-TBM infectious meningitis n = 12, non infectious neurological diseases n = 17).

RESULTS

PCR gave a sensitivity of 91.4% and specificity of 75.9% for the diagnosis of TBM in patients with TBM confirmed by culture. In 16 clinically diagnosed, but unconfirmed, TBM cases PCR was positive in 10 (62.5%) cases. There were seven (24.1%) PCR-positive cases among the 29 patients with non-TBM and non-infectious neurological disease.

CONCLUSIONS

We conclude that the performance of an in-house IS6110 PCR assay is valuable in the rapid diagnosis of tuberculous meningitis.

Tuberculous meningitis (TBM) is the most severe form of tuberculous with substantial mortality. In May 2015, 54 researchers from 10 countries met in Da Lat, Vietnam, to discuss advances in TBM. Among the attendees were researchers involved in pivotal studies on the use of Xpert MTB/Rif for TBM diagnosis. Attendees discussed the 2014 World Health Organization strong recommendation favoring the use of Xpert "in preference to conventional microscopy and culture as the initial diagnostic test for cerebrospinal fluid (CSF) if the sample volume is low or if additional specimens cannot be obtained to make a quick diagnosis." Attendees were concerned that the limitations of Xpert testing for TBM are not emphasized. Clear guidance is needed for the investigational pathway for TBM, including recommendations on the diagnostic package of investigations, which does not stop with Xpert testing. Second, emphasis on the large CSF volumes (ideally 8-10 mL) needed for Xpert testing is required. Guidelines should also emphasize that TBM is a medical emergency and early treatment reduces mortality.