BACKGROUND

The time requirements for multiple daily nebulizer treatments are important impediments to the quality of life for most patients with cystic fibrosis (CF). The I-neb Adaptive Aerosol Delivery (AAD) System can be used with a new mode of breathing during inhalation of aerosol, the Target Inhalation Mode (TIM). As a function of the TIM algorithm, the patient is guided to a slow and deep inhalation, which can result in shorter treatment times.

METHODS

This study was conducted as a 3-month patient handling study of the I-neb AAD System in 42 patients with CF aged 12-57 years. The I-neb AAD System was supplied in both the standard Tidal Breathing Mode (TBM), and in TIM. Patients were trained to use the I-neb AAD System in TIM for the delivery of all their inhaled medications, but if they were not comfortable with the TIM maneuver they could change to the TBM maneuver. The primary variables were compliance with the correct use of the I-neb AAD System, and treatment times. The secondary variables were based on study questionnaires at the end of the study and covered ease of use, patient confidence, and patient satisfaction with the I-neb AAD System.

RESULTS

There were a total of 10,240 complete treatments and of these, 8979 (88%) were in TIM. Compliance with the correct use of the I-neb AAD System was 97.6%. The mean treatment time for complete treatments in TIM was 4.20 min, compared with 6.83 min when using the I-neb AAD System in TBM. The responses to the questionnaires indicated that over 77% of the patients found the I-neb AAD System in TIM to be either: very easy, easy, or acceptable to use.

CONCLUSIONS

The results demonstrated that by using the I-neb AAD System in TIM, a 40-50% reduction of nebulizer treatment times, and a high level of compliance could be achieved. The results also showed that the patients found the I-neb AAD System easy to use.

Defective cell-extracellular matrix (ECM) biophysiology is considered a factor in the development of polycystic kidney disease (PKD). Altered biosynthesis of various ECM components may result in tubular dysmorphogenesis and uncontrolled tubular cystic expansion. In this study, expression of certain ECM components was investigated in a diphenylthiazole (DPT)-induced rat model of PKD. DPT induces cystic change in all the collecting tubules, most severe in the outer medulla and inner cortex, and following withdrawal of DPT, cystic tubules return to normal with persistence of focal interstitial fibrosis. SDS-PAGE analyses of isolated tubular basement membranes (TBMs) of control and PKD kidneys revealed overall similar electrophoretic migratory bands. However, in PKD, there were relative increases in components with M(r) approximately 380,000, 250,000 and 145,000, and a decrease in the component with M(r) approximately 55,000. Immunoblot analyses revealed that the major components of TBM (type-IV collagen, laminin beta 1 and beta 2 chains and entactin) were present in the same relative concentrations in control and PKD. The expression of tubulointerstitial (TIN) antigen was decreased. Also, the relative concentrations of type-I collagen and fibronectin were increased in the PKD group. Following recovery, the expressions of TIN and fibronectin returned to normal, whereas type-I collagen remained elevated. ELISA determinations revealed increased expression of interstitial collagens type-I, -V and -VI in PKD vs control and they remained elevated following recovery, while that of type-III was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

The morphology and kinetics of macrophages and reticulum cells of rat lymph nodes have been studied in relation to the immune response to a second exposure to antigen. During the first 24 h after stimulation monocyte-like exudate macrophages, including some scattered interdigitating cells (IDC), contain granules similar to those present in epidermal Langerhans cells and lymph-borne veiled cells. In this induction phase these macrophages migrate from the marginal sinus into the paracortex and during the migration they gradually transform into IDC. In the proliferation phase the paracortex is mainly populated by transitional macrophages and there are almost no typical IDC present between the lymphoblasts. In the memory phase the relative number of IDC again rapidly increases. During this period in the paracortex there are often typical IDC which contain partially digested necrotic lymphocytes, thus resembling tingible body macrophages (TBM) of the germinal centre in this respect. It is suggested that the newly arrived macrophages induce the lymphoblast reaction, while mature IDC may have an inhibitory function in the memory phase of the immune response. In this phase the phagocytic potential of IDC is clearly shown.

OBJECTIVE

Mycobacterium tuberculosis and Cryptococcus neoformans are major causes of meningitis in HIV-1-infected patients. Identifying differences in the inflammatory profiles of HIV-1-associated tuberculous meningitis (TBM) and cryptococcal meningitis may inform differences in immunopathogenic mechanisms in these diseases. In this study we compared the clinical and inflammatory features of HIV-1-associated TBM, and cryptococcal meningitis.

METHODS

A prospective study of HIV-1-infected adults who presented with either TBM [antiretroviral therapy (ART)-naive] or cryptococcal meningitis (regardless of ART prescription). Clinical and laboratory findings and concentrations of 40 inflammatory mediators measured in cerebrospinal fluid (CSF, 33 paired with blood) were compared between TBM and cryptococcal meningitis patients regardless of ART prescription and between TBM and cryptococcal meningitis patients not receiving ART.

RESULTS

Clinical and laboratory findings were similar in TBM (n=34) and cryptococcal meningitis (n = 19; ART prescribed: n = 10, no ART prescribed: n = 9). Exceptions included a higher median CD4 cell count [interquartile: 113 (69-199) vs. 25 (8-49) cells/μl, P = 0.0001] and higher HIV-1 median viral load [plasma: 5.46 (4.82-5.89) vs. 4.87 (4.36-5.17) log10copies/ml, P = 0.037; CSF: 6.05 (5.43-6.56) vs. 5.56 (4.52-5.80) log10copies/ml, P = 0.03] in TBM vs. cryptococcal meningitis patients not receiving ART. CSF interleukin (IL)-17A was lower in TBM compared with cryptococcal meningitis [1.00 (0.25-2.35) vs. 9.31 (1.24-23.36) pg/ml, P-adjusted = 0.03].

CONCLUSIONS

Despite presenting with higher peripheral CD4 cell counts, TBM patients also presented with higher HIV-1 viral loads compared with cryptococcal meningitis patients, suggesting a greater propensity of M. tuberculosis compared with C. neoformans to increase HIV-1 replication in vivo. CSF IL-17A was lower in TBM; its role in the immunopathogenesis of TBM and cryptococcal meningitis deserves further research.

Many template-based modeling (TBM) methods have been developed over the recent years that allow for protein structure prediction and for the study of structure-function relationships for proteins. One major problem all TBM algorithms face, however, is their unsatisfactory performance when proteins under consideration are low-homology. To improve the performance of TBM methods for such targets, a novel model evaluation method was developed here, and named MEFTop. Our novel method focuses on evaluating the topology by using two novel groups of features. These novel features included secondary structure element (SSE) contact information and 3-dimensional topology information. By combining MEFTop algorithm with FR-t5, a threading program developed by our group, we found that this modified TBM program, which was named FR-t5-M, exhibited significant improvements in predictive abilities for low-homology protein targets. We further showed that the MEFTop could be a generalized method to improve threading programs for low-homology protein targets. The softwares (FR-t5-M and MEFTop) are available to non-commercial users at our website: http://jianglab.ibp.ac.cn/lims/FRt5M/FRt5M.html.

We have developed hybridoma cell lines which secrete monoclonal antibodies to some rat renal antigens, namely the brush border of proximal tubular epithelium and the cytoplasm of tubular cells. The immunoglobulin class of the hybridoma was found to be IgG1. Specific antibody activity against either glomerular basement membrane (GBM) and tubular basement membrane (TBM) or Bowman's capsule and a part of TBM was observed, although these hybridoma cell lines have not yet been successfully established. In particular, the hybridoma secreting antibodies to TBM did not remain stable during antibody production, and was lost during the culture and cloning procedures. These monoclonal antibodies should be of value in research on the pathogenesis of human glomerulonephritis.

Both schizophrenia and antipsychotic treatment are known to modulate brain morphology. However, it is difficult to establish whether observed structural brain abnormalities are due to disease or the effects of treatment. The aim of this study was to investigate the effects of illness and antipsychotic treatment on brain structures in antipsychotic-naïve first-episode schizophrenia based on a longitudinal short-term design. Twenty antipsychotic-naïve subjects with first-episode schizophrenia and twenty-four age- and sex-matched healthy controls underwent 3T MRI scans. Voxel-based morphometry (VBM) was used to examine the brain structural abnormality in patients compared to healthy controls. Nine patients were included in the follow-up examination after 8 weeks of treatment. Tensor-based morphometry (TBM) was used to identify longitudinal brain structural changes. We observed significantly reduced grey matter volume in the right superior temporal gyrus in antipsychotic-naïve patients with schizophrenia compared with healthy controls. After 8 weeks of treatment, patients showed significantly increased grey matter volume primarily in the bilateral prefrontal cortex, insula, right thalamus, left superior occipital cortex and the bilateral cerebellum. In addition, a greater enlargement of the prefrontal cortex is associated with the improvement in negative symptoms, and a more enlarged thalamus is associated with greater improvement in positive symptoms. Our results suggest the following: (1) the abnormality in the right superior temporal gyrus is present in the early stages of schizophrenia, possibly representing the core region related to schizophrenia; and (2) atypical antipsychotics could modulate brain morphology involving the thalamus, cortical grey matter and cerebellum. In addition, examination of the prefrontal cortex and thalamus might facilitate an efficient response to atypical antipsychotics in terms of symptom improvement.

We disagree with the recommendation by the World Health Organization to use Xpert(®) MTB/RIF on cerebrospinal fluid for the initial diagnosis of tuberculous meningitis (TBM). TBM is a devastating disease requiring empirical treatment even when the probability of disease is low. We suggest that a useful TBM diagnostic test needs a negative predictive value (NPV) of ⩾ 99% so that empirical treatment can be stopped safely. The NPV of Xpert is around 84%, making a negative test of limited value. While better tests are awaited, a composite score, possibly combining Xpert with clinical variables and with high NPV, should be constructed and validated prospectively.

Twelve cases of tracheobronchomalacia (TBM) cases were reviewed: five were pediatric, and seven were adult, two of which were due to relapsing polychondritis (RPC). In pediatric TBM, the malacic segments were short. Resection of the malacic segment in one case and laryngotracheoplasty with autologous costal cartilage in one case were unsuccessful. However, aortopexy gained good results. Two cases managed conservatively experienced gradual improvement of their symptoms. In adult TBM, plication of pars membranacea was not effective in one case. The insertion of a stent was minimally effective in one case, and distinctly in one polychondritic case. The other four cases managed conservatively have deteriorated gradually. From these findings, a new classification system is proposed.

METHODS

The prognosis of tuberculous meningitis (TBM) is linked to early diagnosis and prescription of adequate treatment.

OBJECTIVE

To evaluate the efficacy of the rpoB nested polymerase chain reaction (PCR) and sequencing assay to detect and identify Mycobacterium tuberculosis complex (MTC) strains and strains resistant to rifampicin (RMP) in cerebrospinal fluid specimens (CSF) from patients with highly suspected TBM.

METHODS

Retrospective blinded hospital-based study.

RESULTS

rpoB nested PCR and sequencing assay detected MTC in 31/36 CSF specimens from 16 patients with clinically suspected TBM. All of the control CSF specimens from 25 patients with non-TBM showed negative results. One of the 16 patients had a mutation at codon C526G as compared to the rpoB sequences in GenBank. This corresponds to a diagnostic sensitivity of 86% (95%CI 71-95) and a specificity of 100% (95%CI 86-100).

CONCLUSIONS

Our results suggest that rpoB nested PCR and sequencing assay can detect MTC and simultaneously determine its RMP susceptibility in CSF from patients with highly suspected TBM.

BACKGROUND

Early treatment is critical to reducing tuberculous meningitis (TBM) related morbidity and mortality. Diagnosis based on cerebrospinal fluid (CSF) culture is impractical due to slow turnaround times, while microscopy has poor sensitivity. Enhanced detection methods are essential to guide early treatment initiation, especially in vulnerable young children.

METHODS

We assessed the diagnostic accuracy of the GenoType(®) MTBDRplus and Xpert(®) MTB/RIF assays on CSF collected from paediatric meningitis suspects prospectively enrolled at Tygerberg Hospital, Cape Town, South Africa. Fluorescent auramine-O microscopy, liquid culture for Mycobacterium tuberculosis, GenoType and Xpert assays were performed on all CSF samples.

RESULTS

Of 101 meningitis suspects, 55 were diagnosed with TBM and 46 served as non-TBM controls. Using a pre-defined TBM case definition as reference standard, sensitivities and specificities were 4% and 100% for fluorescent microscopy, 22% and 100% for culture, 33% and 98% for GenoType, 26% and 100% for Xpert, 22% and 100% for microscopy and culture combined and 49% and 98% for GenoType and Xpert combined. Culture, GenoType and Xpert combined performed best, with 56% sensitivity and 98% specificity.

CONCLUSIONS

Although commercial nucleic-acid amplification tests performed on CSF revealed incrementally improved diagnostic accuracy, providing rapid microbiological confirmation, they cannot serve as a rule-out test.

BACKGROUND

The prevalence of tuberculous meningitis (TBM) is very high in developing areas of the world. Inflammation and cytokine patterns produced by T lymphocytes play an important role in susceptibility to infections. The inflammatory response and production of cytokines in the cerebrospinal fluid (CSF) of patients with TBM are well documented. Conversely, little is known about the role of pro- and anti-inflammatory cytokines in the CSF of TBM patients. The goal of the present study was to estimate the level of proinflammatory cytokine and anti-inflammatory cytokine levels in CSF samples from TBM patients.

METHODS

To study this, in vivo levels of IL-2 and IFN-gamma (proinflammatory cytokines), and IL-10 (anti-inflammatory cytokine) in the CSF of 60 adult TBM patients and 50 age- and sex-matched non-TBM controls were measured. These cytokines were estimated in the CSF of TBM patients before and after starting treatment.

RESULTS

High levels of proinflammatory cytokines as compared to anti-inflammatory cytokines were found in TBM patients before treatment. However, CSF samples from TBM patients after treatment showed elevated levels of anti-inflammatory and low levels of proinflammatory cytokines.

CONCLUSIONS

We hypothesize that an increase in anti-inflammatory cytokines during treatment may indicate a favorable response.

BACKGROUND

Among the various forms of TB, tuberculous meningitis (TBM) is the most severe, with about 30% mortality and 50% of survivors left with neurological sequelae. Children suffer more frequently from TBM than adults and outcomes are often poor due to difficulties in making the diagnosis and uncertainty regarding the best anti-tuberculosis drug regimen. The aim of this prospective study was to describe the pharmacokinetics of pyrazinamide, isoniazid and rifampicin in plasma and cerebrospinal fluid of children with tuberculous meningitis treated with the standard TBM regimen.

METHODS

We performed a prospective observational study of 100 consecutively treated children (≤ 15 years of age) with tuberculous meningitis in Ho Chi Minh City, Vietnam. Children were treated according to the 2006 WHO recommended pediatric treatment regimen consisting of isoniazid (5 mg/kg), rifampicin (10 mg/kg) and ethambutol (15 mg/kg) for 8 months, with the addition of pyrazinamide (25 mg/kg) for the first 3 months and streptomycin (15 mg/kg) for the first 2 months. Pyrazinamide, isoniazid and rifampicin concentrations were measured in plasma at day 14 and in cerebrospinal fluid (CSF) at 1 month by HPLC-UV. A naïve-pooled non-compartmental data analysis was used to describe the pharmacokinetic properties of drugs in the two-age groups of children ≤ 4 years or>> 4 years of age.

RESULTS

Younger children, when compared to older children, presented a higher body weight-normalized clearance and volume of distribution, and lower median total plasma exposures for the three studied drugs with -14%, -22% and -16% for Pyrazinamide, Isoniazid and Rifampicin, respectively. In CSF, individual concentrations of isoniazid and pyrazinamide were comparable to that in plasma in both age groups; but rifampicin concentrations were lower than the minimum inhibitory concentration of susceptible bacteria in all but two children.

CONCLUSIONS

There is an age-dependent variation in the plasma and cerebrospinal fluid pharmacokinetics of rifampicin, isoniazid and pyrazinamide. The safety and efficacy of higher doses of rifampicin should be investigated for the treatment of childhood tuberculous meningitis.

OBJECTIVE

To estimate the incidence of culture-positive and culture-negative tuberculous meningitis (TBM) in France in 2000.

METHODS

Capture-recapture method using two unrelated sources of data: the tuberculosis (TB) mandatory notification system (MNTB), recording patients treated by anti-tuberculosis drugs, and a survey by the National Reference Centre (NRC) for mycobacterial drug resistance, recording culture-positive TBM.

RESULTS

Of 112 cases of TBM reported to the MNTB, 28 culture-positive and 34 culture-negative meningitis cases were validated (17 duplicates, 3 cases from outside France, 21 false notifications, and 9 lost records were excluded). The NRC recorded 31 culture-positive cases, including 21 known by the MNTB. When the capture-recapture method was applied to the reported culture-positive meningitis cases, the estimated number of meningitis cases was 41 and the incidence was 0.7 cases per million. Sensitivity was 75.6% for the NRC, 68.3% for the MNTB, and 92.7% for both systems together. When sensitivity of the MNTB for culture-positive cases was applied to culture-negative meningitis, the total estimated number of culture-negative meningitis cases was 50 and the incidence was 0.85 cases per million.

CONCLUSIONS

TBM is underestimated in France. Capture-recapture analysis using different sources to better estimate its incidence is of great interest.

Pediatric tuberculous meningitis (TBM) leads to high rates of mortality and morbidity. Prompt diagnosis and initiation of treatment are challenging; imaging findings play a key role in establishing the presumptive diagnosis. General brain imaging findings are well reported; however, specific data on cerebral vascular and spinal involvement in children are sparse.

This prospective cohort study examined admission and followed up computed tomography brain scans and magnetic resonance imaging scans of the brain, cerebral vessels (magnetic resonance angiogram) and spine at 3 weeks in children treated for TBM with hydrocephalus (HCP; inclusion criteria). Exclusion criteria were no HCP on admission, treatment of HCP or commencement of antituberculosis treatment before study enrollment. Imaging findings were examined in association with outcome at 6 months.

Forty-four patients (median age 3.3 [0.3-13.1] years) with definite (54%) or probable TBM were enrolled. Good clinical outcome was reported in 72%; the mortality rate was 16%. Infarcts were reported in 66% of patients and were predictive of poor outcome. Magnetic resonance angiogram abnormalities were reported in 55% of patients. Delayed tuberculomas developed in 11% of patients (after starting treatment). Spinal pathology was more common than expected, occurring in 76% of patients. Exudate in the spinal canal increased the difficulty of lumbar puncture and correlated with high cerebrospinal fluid protein content.

TBM involves extensive pathology in the central nervous system. Severe infarction was predictive of poor outcome although this was not the case for angiographic abnormalities. Spinal disease occurs commonly and has important implications for diagnosis and treatment. Comprehensive imaging of the brain, spine and cerebral vessels adds insight into disease pathophysiology.

Total bone mineral and bone mineral density modifications were evaluated during fracture healing of long bones in patients with traumatic fractures of the lower limbs, using an experimental model based on the dual photonabsorptiometry technique. Seven patients (five males and two females; mean age, 19.5 years; range, 17-23 years) with tibia and fibula midshaft open fractures treated with osteosynthesis were studied. Dual energy gadolinium-153 photonabsorptiometry was used to measure distal leg bone loss at a skeletal segment distant from the fracture to exclude callus formation. Total bone mineral (TBM) and bone mineral density (BMD) of the tibia and fibula both in the fractured leg and in the healthy contralateral leg were measured on Days 10, 20, 30, 40, 60, and 120 after trauma. TBM and BMD of the healthy contralateral leg did not present any significant modifications at the different observation times. Both TBM and BMD of the fractured leg showed a progressive reduction that reached statistical significance starting on Day 30 with maximum reduction on Day 120 when TBM and BMD were reduced to almost one-half the initial value.

A prospective hospital based study was undertaken to study the effect of methyl prednisolone therapy on sensory and motor functions in tuberculous meningitis (TBM). The patients with TB meningitis seen during 1994-1998 were studied. CT scan, motor evoked potential (MEP) to upper and lower limbs; and median and tibial somatosensory evoked potentials (SEP) were carried out in all the patients. Outcome was defined at the end of 3 months into poor, partial or complete recovery on the basis of Barthel index score. Inj methyl prednisolone (MPS) 500 mg IV was given to 21 patients followed by oral tapering dose of prednisolone over one month in addition to 4 drug anti-tubercular treatment. The control group comprised of 16 patients who received 4 drugs anti-tubercular therapy without any corticosteroid. These groups were comparable with respect to their age, stage of meningitis, Glasgow coma scale score and radiological findings. In MPS group, CMCT was abnormal in 9 and SEPs in 7 patients. In the control group, these were abnormal in 9 and 5 patients respectively. Three months after the therapy the frequency of improvement, deterioration and stationary evoked potential (EP) changes were also noted in both the groups. Diversity of evoked potential changes were also noted. Evoked potential changes were neither significantly different between the groups nor there was any beneficial effect shown in MPS group at 3 months. On the contrary, the control group fared significantly better than the MPS group. Initial MEP and SEP abnormalities were however related to 3 months outcome (p<0.01).

Linear and granular tubular basement membrane (TBM) deposits of C3 occur in renal allograft biopsies, but their significance is unknown. We retrospectively analyzed the predictive importance of C3 deposits in 88 biopsied transplant patients with allograft dysfunction. All patients were followed for greater than or equal to 2 years from biopsy. Patients were divided into three groups: group I: no C3 deposits, 47 patients; group II: granular deposits of C3, 28 patients; and group III: linear TBM deposits, 13 patients. The incidence of acute and chronic rejection was not different. In group III, 12 grafts were lost by 5 years (92%), and the remaining patient has chronic rejection. Group III survival was significantly less than groups I and II (Kaplan-Meier curves), P = 0.02, but graft survival in groups I and II were similar. There was no association of anti-TBM antibody deposits with C3, and the mechanism of deposition is unknown. We conclude that the presence of linear C3 deposits along the TBM in the setting of allograft dysfunction is associated with decreased allograft survival.

The present study has been undertaken to describe brainstem auditory evoked potential (BAEP) changes in tubercular meningitis (TBM) and correlate these with CT scan and MRI findings. 24 patients with TBM were subjected to clinical evaluation and CT scan or MRI study. Outcome was defined by 3 month Barthel index score (BI) into poor (BI<12) and good (BI>or=12). The mean age of patients was 26.4+/-14.9 (range 10-62) years, 8 of them were females. Sixteen patients were in stage III, 5 in stage II and 3 in stage I meningitis. CT scan revealed hydrocephalus in 16, exudate in 9, infarction in 12 and tuberculoma in 3 patients. Brainstem was involved in 3 patients (2 infarction and 1 granuloma). BAEPs were unrecordable in one patient and abnormal in 15. The absolute latencies and inter peak latency (IPL) however were not significantly affected. The wave V/I amplitude ratio was abnormal on 12 sides. The BAEP abnormalities were not related to the stage of meningitis, level of consciousness, any specific CT or MRI changes or outcome at 3 months.

OBJECTIVE

Tuberculous meningitis (TBM) is a massive global problem. The mortality and morbidity associated with the severe form of the disease are exceptionally high. Even when increased intracranial pressure is treated and full conventional therapy is commenced, cerebral ischemia can develop and is associated with a particularly poor prognosis. We sought to evaluate our experience with two patients with severe TBM and cerebral oxygenation monitoring.

METHODS

Case report.

METHODS

Red Cross Children's Hospital, Cape Town.

METHODS

Two comatose patients with TBM.

METHODS

Targeted interventions against low cerebral oxygenation in one patient.

RESULTS

Cerebral tissue oxygenation (Ptio2) was measured. In both patients, Ptio2 monitoring demonstrated delayed cerebral ischemia despite the institution of full conventional therapy and the control of intracranial pressure. These data confirm that the vascular involvement in TBM is potentially progressive and that failure to diagnose infarction initially is not merely due to a delay in the radiologic appearance. The first patient developed extensive infarction, consistent with Ptio2 readings, and subsequently died after treatment withdrawal. Intervention in the second patient successfully reversed a precipitous decline of the Ptio2 readings and may have prevented infarction in this patient.

CONCLUSIONS

The development of delayed cerebral ischemia in TBM despite treatment is confirmed in these two patients. The reversal of a decline in Ptio2 readings suggests a possible benefit for cerebral oxygenation monitoring in selected patients with severe TBM.

OBJECTIVE

This study aimed to evaluate linear measurements and computerized volumetric ratios on axial magnetic resonance imaging (MRI) scans against the diagnosis of hydrocephalus in children with tuberculous meningitis (TBM).

METHODS

MRI scans and clinical notes of children with culture positive TBM were reviewed. Patients with surgical drainage of ventricles were considered positive for hydrocephalus. Alternatively, predefined radiological criteria of hydrocephalus in combination with any clinical criteria were considered positive for hydrocephalus. Axial T2-weighted MRI scans were used for measurement by a radiologist. Linear measurements included the Evans index, frontal-occipital horn ratio, and frontal-occipital horn width ratio. Computer-assisted segmentation of the MRI volume was performed on a slice-by-slice basis using the number of pixels comprising each region to calculate the ratios: ventricular volume: brain volume and cerebrospinal fluid (CSF)/(brain + CSF) for all slices and for a single slice at the level of the lateral ventricles.

RESULTS

Twenty-two children (mean age 3.7 years) comprised ten patients with a 'final' diagnosis of hydrocephalus (six communicating, four non-communicating). None of the linear measurements showed a statistical correlation with the 'final' diagnosis of hydrocephalus. The frontal-occipital horn width ratio (FOHWR) (p = 0.09) was the closest to demonstrate statistical significance. The highest sensitivity was attained with FOR (90%) followed by FOHWR (85%). The highest specificity was reached with FOHWR (70%). Volumetric ratios were inferior to linear measures.

CONCLUSIONS

Linear measures of hydrocephalus in TBM were more reliable than volumetric ratios. Hydrocephalus can be quantified most reliably using the FOHWR. This is useful for serial follow-up and for research of TBM.

BACKGROUND

Early diagnosis of tuberculous meningitis (TBM) is still a challenge; the present study aimed to establish a method of detecting the antigen early secreted antigenic target 6 (ESAT-6) in cerebrospinal fluid (CSF) by an indirect enzyme-linked immunosorbance assay (ELISA) protocol and to study the value of detecting ESAT-6 in CSF in the early diagnosis of TBM.

METHODS

An indirect ELISA protocol was used, employing a monoclonal antibody (mAb) against ESAT-6, which was used to demonstrate ESAT-6 in the CSF from TBM patients and non-TBM controls. CSF was obtained from 100 patients: confirmed TBM, clinically diagnosed TBM, disease controls, and healthy controls (n = 10). Pure recombinant ESAT-6 (standard product) was used in serial dilutions to detect the absorbance and to establish a standard curve from the data; the concentration was on the X axis vs. absorbance on the Y axis, and the standard curve was used to interpolate the concentration of ESAT-6 in samples.

RESULTS

The indirect ELISA method provided 88 % sensitivity and 92 % specificity for the diagnosis of TBM using a mAb to ESAT-6. The mean concentration of ESAT-6 in TBM patients was significantly higher than that of the non-TBM groups. There was also a significant difference in the mean ESAT-6 expression between the confirmed TBM patients and the clinically diagnosed TBM patients (p < 0.01).

CONCLUSIONS

Detection of ESAT-6 in the CSF of TBM patients by indirect ELISA protocol gives a reliable early diagnosis and can be used to develop an immunodiagnostic assay with increased sensitivity and specificity.

The decomposition of trihaloacetic acids [bromodichloroacetic acid (BDCAA), dibromochloroacetic acid (DBCAA), tribromoacetic acid (TBAA)], and the formation of the corresponding trihalomethanes [bromodichloromethane (BDCM), dibromochloromethane (DBCM), tribromomethane (TBM)] were studied. Like TBAA, the two mixed chlorobromo-species, BDCAA and DBCAA, were found to decompose to form BDCM and DBCM, respectively, via a decarboxylation pathway. The decomposition of BDCAA, DBCAA and TBAA in water at neutral pH follows a first-order reaction, with rate constants of 0.0011, 0.0062 and 0.040 day(-1) at 23 degrees C, respectively; and 0.000028, 0.00014 and 0.0016 day(-1) at 4 degrees C, respectively. The activation energies for the decomposition reaction of BDCAA, DBCAA and TBAA in water at neutral pH were found to be 35.0, 34.5 and 29.2 kcal/mol, respectively. The effect of pH in the range of 6-9 and the effect of a drinking water matrix on the decomposition of BDCAA, DBCAA, and TBAA in water were found to be insignificant. Measurement and health implications due to decomposition of trihaloacetic acids and formation of the corresponding trihalomethanes were discussed. By applying the technique of quantitative structure-activity relationships (QSAR), the decomposition rate constants of six iodinated trihaloacetic acids were estimated.

BACKGROUND

The diagnosis value of adenosine deaminase (ADA) activity in cerebrospinal fluid (CSF) of tuberculous meningitis (TBM) has been well documented. However, the cutoff point of CSF ADA has not been fully assessed. In the current study, the authors set to calculate the cutoff points of ADA and monitor the changes of CSF ADA activities in patients with TBM after antitubercular therapy.

METHODS

CSF ADA activity in patients with different types of meningitis was measured by Trinder enzyme-coupled assay.

RESULTS

The mean CSF ADA values in the patients with TBM, bacterial meningitis, viral meningitis, cryptococcal meningitis and noninfectious neurologic disorders were 14.1 ± 5.4, 9.6 ± 5.5, 4.3 ± 2.5, 7.8 ± 3.4 and 2.6 ± 1.3 U/L, respectively. CSF ADA activity was significantly higher in TBM compared with patients with non-TBM (P < 0.05). Moreover, the best cutoff point for differentiating between TBM and non-TBM was 9.5 U/L. In addition, CSF ADA activity was decreased in patients with TBM after antitubercular therapy in a time-dependent manner.

CONCLUSIONS

The determination of ADA with a cutoff value of 9.5 U/L in CSF is a useful aid for the differential diagnosis of TBM and non-TBM. Moreover, dynamic monitoring of CSF ADA activity may be an indicator for evaluating antitubercular therapy in TBM.