Tuberculous meningitis (TBM) is an outcome of neuroinflammatory degeneration caused due to Mycobacterium tuberculosis infection and leads to death or neurological disabilities in the affected individuals. It causes the highest morbidity and mortality amongst all forms of tuberculosis. Matrix metalloproteinase-9 levels increase and cause inflammatory destruction during progression of the disease. Although corticosteroids are usually given as an adjuvant therapy to overcome these complications, treatment outcome is contradictory. This study was designed to evaluate whether specific inhibition of MMP-9 can be beneficial in management of the disease. MMP-9 levels were inhibited using SB-3CT or dexamethasone along with conventional drugs for treatment of tuberculous meningitis. Both SB-3CT and dexamethasone decreased the elevated levels of MMP-9 in sera and tissues of the infected mice. However, dexamethasone administration had an inhibitory effect on bacillary clearance, while SB-3CT potentiated the bacillary clearance, suggesting that MMP-9, if specifically inhibited, can be beneficial in the management of TBM.

Murine models of tuberculous meningitis (TBM) have not reflected the severity of disease in humans. Based on reports that activated murine microglial cells, but not human microglial cells, express inducible nitric oxide synthase (iNOS), the objective of this study was to determine whether iNOS-knockout (iNOS(-/-)) mice would provide such a model. iNOS(-/-) mice infected with M. tuberculosis developed serious clinical manifestations and granulomatous lesions containing tubercle bacilli throughout the meninges, all of which were absent in wild-type mice. This study underscores the importance of nitric oxide in defense against TBM and suggests that iNOS(-/-) mice are an appropriate model for human TBM.

UNASSIGNED

The objective of this study was to compare safety and efficacy of endoscopic third ventriculostomy (ETV) versus ventriculoperitoneal (VP) shunt in the treatment of hydrocephalus in tuberculous meningitis (TBM) and to assess clinical and radiological profiles of patients with TBM that would be better suited to either VP shunt or ETV.

UNASSIGNED

This study was a single-center randomized prospective study on 52 patients with TBM hydrocephalus in the pediatric age group (<18 years of age). Patients included in the study were randomized into undergo either VP shunt or ETV. Both groups were followed up for a minimum of 5 months and assessed for success and failure rates as well as procedural complications and neurologic sequelae.

UNASSIGNED

Twenty-six patients underwent ETV with a success rate of 65.4% with six of nine failures occurring within the first 16 days after surgery (median time to failure - 3 days). In the VP shunt group, there was a success rate of 61.54% and a median time to failure of 50 days. Modified Vellore grading was found to be a significant factor in determining outcome in both ETV and VP shunt groups with high-grade TBM consistently associated with poor outcome (odds ratio = 4.2).

UNASSIGNED

ETV can be performed effectively in young children including infants, as well as those with communicating hydrocephalus, high cerebrospinal fluid (CSF) cell counts, and protein levels with a lower rate of failure than that of VP shunt. Hence, ETV should be attempted as the first-choice CSF diversion procedure in hydrocephalus secondary to TBM where technical expertise and experience with this procedure is available as it avoids the myriad of lifelong complications associated with shunts.

One of the most consistently reported brain abnormalities in schizophrenia (SCZ) is decreased volume and shape deformation of the hippocampus. However, the potential contribution of chronic antipsychotic medication exposure to these phenomena remains unclear.

We examined the effect of chronic exposure (8 weeks) to clinically relevant doses of either haloperidol (HAL) or olanzapine (OLZ) on adult rat hippocampal volume and shape using ex vivo structural MRI with the brain retained inside the cranium to prevent distortions due to dissection, followed by tensor-based morphometry (TBM) and elastic surface-based shape deformation analysis. The volume of the hippocampus was also measured post-mortem from brain tissue sections in each group.

Chronic exposure to either HAL or OLZ had no effect on the volume of the hippocampus, even at exploratory thresholds, which was confirmed post-mortem. In contrast, shape deformation analysis revealed that chronic HAL and OLZ exposure lead to both common and divergent shape deformations (q = 0.05, FDR-corrected) in the rat hippocampus. In particular, in the dorsal hippocampus, HAL exposure led to inward shape deformation, whereas OLZ exposure led to outward shape deformation. Interestingly, outward shape deformations that were common to both drugs occurred in the ventral hippocampus. These effects remained significant after controlling for hippocampal volume suggesting true shape changes.

Chronic exposure to either HAL or OLZ leads to both common and divergent effects on rat hippocampal shape in the absence of volume change. The implications of these findings for the clinic are discussed.

BACKGROUND

Though animal studies have suggested a role for proinflammatory cytokines in pathogenesis their exact role in pathogenesis of human meningeal tuberculosis continues to be controversial with different studies yielding contradictory results.

OBJECTIVE

To study the levels of proinflammatory cytokines in serum and cerebrospinal fluid (CSF) of patients with tubercular meningitis (TBM) and to determine whether these correlate with disease severity.

METHODS

Present study included 146 patients with TBM (90- Definite TBM; 56- Probable TBM), diagnosed according to criteria laid by Ahuja et al. which were modified to include CSF nucleic acid based tests. Serum (n=146) and CSF (n=140) levels of various proinflammatory cytokines (IL-1β, IL-2, IL-6, TNF-α and IFNγ) were compared between TBM patients and healthy volunteers (n=99). These levels were correlated with various clinical, radiological and CSF parameters of TBM patients.

RESULTS

Proinflammatory cytokines include cytokines which promote systemic inflammation. In current study, the serum and CSF levels of various cytokines (IL-2, IL-4, IL-6, IL-1β, IFN-γ and TNF-α) were significantly elevated in TBM patients compared to controls. A significant correlation was found between a) Higher stage of TBM and various cytokines (except for serum IL-6 and CSF IFN-γ); b) High CSF TNF-α, IL-4 and IL-1β with severity of hydrocephalus; c) High CSF IL1β and IFN-γ with presence of exudates on MRI; d) Serum and CSF levels of all cytokines with poor outcome as determined by death or as defined by S and E ADL (Schwab and England activities of daily living) score or by GOS (Glasgow outcome scale) (except for interferon gamma); and e) Serum and CSF IL-4 and IL1β with presence of infarcts on MRI brain.

CONCLUSIONS

Proinflammatory cytokines play an important role in the pathogenesis of TBM and contribute significantly towards severity of disease.

Traumatic brain injury (TBI) is a significant public health concern, and can be especially disruptive in children, derailing on-going neuronal maturation in periods critical for cognitive development. There is considerable heterogeneity in post-injury outcomes, only partially explained by injury severity. Understanding the time course of recovery, and what factors may delay or promote recovery, will aid clinicians in decision-making and provide avenues for future mechanism-based therapeutics. We examined regional changes in brain volume in a pediatric/adolescent moderate-severe TBI (msTBI) cohort, assessed at two time points. Children were first assessed 2-5 months post-injury, and again 12 months later. We used tensor-based morphometry (TBM) to localize longitudinal volume expansion and reduction. We studied 21 msTBI patients (5 F, 8-18 years old) and 26 well-matched healthy control children, also assessed twice over the same interval. In a prior paper, we identified a subgroup of msTBI patients, based on interhemispheric transfer time (IHTT), with significant structural disruption of the white matter (WM) at 2-5 months post injury. We investigated how this subgroup (TBI-slow, N = 11) differed in longitudinal regional volume changes from msTBI patients (TBI-normal, N = 10) with normal WM structure and function. The TBI-slow group had longitudinal decreases in brain volume in several WM clusters, including the corpus callosum and hypothalamus, while the TBI-normal group showed increased volume in WM areas. Our results show prolonged atrophy of the WM over the first 18 months post-injury in the TBI-slow group. The TBI-normal group shows a different pattern that could indicate a return to a healthy trajectory.

To understand how red blood cell and other proteins carry out their functions, it is necessary not only to have high-resolution crystal structures, but also to have methods that can measure changes in position of parts of the protein on the scale of Angstroms. The method of luminescence resonance energy transfer (LRET) has considerable advantages for this purpose, particularly for proteins, such as the AE1 anion exchange protein in the red cell, that are homodimers. We have applied this method, using a terbium maleimide chelate (TbM) as donor and fluorescein maleimide (FM) as acceptor, to measure the distance between the C201 residues in adjacent dimerized cytoplasmic domains of AE1 (cdAE1). The distance measured by LRET (40.8 A) corresponds closely with that calculated from the crystal structure of the cdAE1, indicating that the method can provide useful information for testing hypotheses concerning motions in this and other blood cell proteins.

The tensor-based morphometry (TBM) has been widely used in characterizing tissue volume difference between populations at voxel level. We present a novel computational framework for investigating the white matter connectivity using TBM. Unlike other diffusion tensor imaging (DTI) based white matter connectivity studies, we do not use DTI but only T1-weighted magnetic resonance imaging (MRI). To construct brain network graphs, we have developed a new data-driven approach called the ε-neighbor method that does not need any predetermined parcellation. The proposed pipeline is applied in detecting the topological alteration of the white matter connectivity in maltreated children.

OBJECTIVE

Neuropsychologists frequently include proverb interpretation as a measure of executive abilities. A concrete interpretation of proverbs, however, may reflect semantic impairments from anterior temporal lobes, rather than executive dysfunction from frontal lobes. The investigation of proverb interpretation among patients with different dementias with varying degrees of temporal and frontal dysfunction may clarify the underlying brain-behavior mechanisms for abstraction from proverbs. We propose that patients with behavioral variant frontotemporal dementia (bvFTD), who are characteristically more impaired on proverb interpretation than those with Alzheimer's disease (AD), are disproportionately impaired because of anterior temporal-mediated semantic deficits.

METHODS

Eleven patients with bvFTD and 10 with AD completed the Delis-Kaplan Executive Function System (D-KEFS) Proverbs Test and a series of neuropsychological measures of executive and semantic functions. The analysis included both raw and age-adjusted normed data for multiple choice responses on the D-KEFS Proverbs Test using independent samples t-tests. Tensor-based morphometry (TBM) applied to 3D T1-weighted MRI scans mapped the association between regional brain volume and proverb performance. Computations of mean Jacobian values within select regions of interest provided a numeric summary of regional volume, and voxel-wise regression yielded 3D statistical maps of the association between tissue volume and proverb scores.

RESULTS

The patients with bvFTD were significantly worse than those with AD in proverb interpretation. The worse performance of the bvFTD patients involved a greater number of concrete responses to common, familiar proverbs, but not to uncommon, unfamiliar ones. These concrete responses to common proverbs correlated with semantic measures, whereas concrete responses to uncommon proverbs correlated with executive functions. After controlling for dementia diagnosis, TBM analyses indicated significant correlations between impaired proverb interpretation and the anterior temporal lobe region (left>right).

CONCLUSIONS

Among two dementia groups, those with bvFTD, demonstrated a greater number of concrete responses to common proverbs compared to those with AD, and this performance correlated with semantic deficits and the volume of the left anterior lobe, the hub of semantic knowledge. The findings of this study suggest that common proverb interpretation is greatly influenced by semantic dysfunction and that the use of proverbs for testing executive functions needs to include the interpretation of unfamiliar proverbs.

Renal tubular dysfunction was induced in Hartley guinea pigs by injection of sodium aurothiomalate (gold) as manifested by excretion of tubular basement membrane (TBM) antigen and renal tubular epithelial (RTE) antigen in urine and tubular proteinuria. Following the tubular dysfunction, autoimmune tubulointerstitial nephritis (TIN) and/or immune complex nephropathy (ICN) developed in a large proportion of animals. TIN was associated with anti-TBM antibodies, and the histological features were characterized by tubular lesions with interstitial mononuclear cell infiltration, destruction of tubules, and interstitial fibrosis. In ICN, the glomerular lesions consisted of partial thickening of capillary walls and mesangial cellularity, and granular immune deposits were seen in the mesangial area and on capillary walls. Furthermore, electron-dense deposits were demonstrated in the mesangial area and in the glomerular basement membrane (GBM) by electron microscopy. Anti-RTE antibodies were detected in the sera and eluates from the kidney of animals with ICN. RTE antigens were also detected in the glomerular deposits by indirect immunofluorescence using anti-guinea pig RTE antibody. These results suggest that TBM and RTE antigens released from renal tubules damaged by a direct toxic action of gold may lead to antibody formation against these antigens and induce TIN and/or ICN.

Enzyme-linked immunosorbent assay of immunoglobulin G (IgG) activity in cerebrospinal fluid (CSF) and sera was conducted prospectively in 27 patients with tuberculous meningitis (TBM) by using purified protein derivative (PPD) and lipoarabinomannan (LAM) antigens, from January 1989 to August 1990. 29 patients with aseptic meningitis and 49 patients with non-inflammatory neurological illnesses served as controls. All patients had a computed tomography (CT) scan of the head before a lumbar puncture. The IgG antibodies to the antigens were significantly elevated in TBM, and the reactivity was more frequently positive in the CSF than in the sera, suggesting a local synthesis of IgG in the central nervous system (CNS). The sensitivity and the specificity for the diagnosis of TBM were 59.2% and 93.9% for PPD antigen, and 85.2% and 95.9% for LAM antigen, respectively. Assay of IgG reactivity to LAM antigen was clinically very useful for the early diagnosis of TBM and was superior to PPD for detecting the serological evidence of TBM.

The sensitivity and specificity of immunocytochemical staining of mycobacterial antigens in the cytoplasm of cerebrospinal fluid (CSF) macrophages for diagnosis of tuberculous meningitis (TBM) was prospectively compared with Ahuja criteria from 393 consecutive CSF specimens. The assay can play an important role for the diagnosis of TBM, with sensitivity of 73.5% and specificity of 90.7%.

BACKGROUND

Hydrocephalus secondary to tuberculous meningitis (TBM) continues to be a challenging condition to treat for neurosurgeons in developing countries. Shunt complications are reportedly more frequent in patients undergoing ventriculo-peritoneal shunt in patients with TBM than in those undergoing shunt surgeries for other causes.

OBJECTIVE

The aim of this study was to evaluate the relationship of cerebrospinal fluid (CSF) composition on shunt malfunction.

METHODS

We compared the CSF composition of 53 patients who had shunt malfunction during a five year period with that of 137 matched controls.

RESULTS

Patients who had shunt malfunction had a significantly higher concentration of CSF protein. The CSF cellularity and glucose concentration did not have any significant bearing in predicting shunt malfunction. Patients with CSF protein concentration of more than 200 mg/dL had a four times higher risk of having shunt malfunction than those with a concentration of less than 100 mg/dL. Patients with CSF protein in the 100-200 mg/dL range represent an intermediate zone.

CONCLUSIONS

To conclude, patients with CSF protein concentration of more than 200 mg/dL have a significantly higher risk of shunt malfunction and hence have to be followed up closely.

OBJECTIVE

To demonstrate the detailed imaging characteristics of early tuberculous meningitis (TBM) and changes over time on standard gadolinium-enhanced, T1-weighted magnetic resonance imaging (MRI) images.

METHODS

Contrast-enhanced, T1-weighted, spin-echo MRI images of 26 patients with early TBM were evaluated retrospectively. Meningeal enhancement characteristics were categorized according to distribution and pattern as diffuse, focal, linear, nodular, and mixed.

RESULTS

We found that 35% of patients had diffuse meningeal enhancement and 65% of cases had focal meningeal enhancement. There was a predilection for focal meningeal enhancement in basal pial areas, the interpeduncular fossa being the most common. In six patients with diffuse meningeal enhancement admitted to hospital relatively early after the onset of symptoms, the type of meningeal enhancement later changed to the focal form.

CONCLUSIONS

Reactive diffuse meningeal enhancement occurs in the early period of TBM on contrast medium-enhanced T1-weighted MR images, but later becomes limited to basal areas.

OBJECTIVE

Studies have been done that have focused on the efficacy of bacillus Calmette-Guérin (BCG) vaccination in the prevention of cases of childhood tuberculous meningitis (TBM). However the efficacy of the vaccination in the prevention of mortality has not been sufficiently evaluated. This study aimed to determine the main features of TBM cases in childhood and to evaluate the factors related to mortality, proving the protective effect of BCG vaccination in childhood TBM.

METHODS

In a retrospective approach, all consecutive cases of TBM in children that occurred between 1997 and 2005, at Dicle University Hospital, were studied. The following data were evaluated: demographic aspects, admission symptoms, radiology and laboratory findings, BCG vaccination status, tuberculin skin test (TST) positivity, and mortality rates.

RESULTS

In total, 172 cases of childhood TBM were evaluated (mean age 53.3±55.7 months; 109 boys (63.4%)). The majority of these cases (70.4%) had typical TBM symptoms on admission. BCG vaccination data were available for 152 (88.4%) cases and 29 of them (19.1%) were positive. The TST was performed for 143 patients (83.1%) and 28 (19.6%) were found positive. Hydrocephalus was identified in 118 patients (68.6%) on computed tomography examination. A shunt was placed in 79 cases (45.9%). In total, 24 patients (14.0%) died in the hospital. TST negativity was a significant factor for mortality (p=0.012). BCG positivity was found to be a preventive factor from mortality (p=0.05).

CONCLUSIONS

BCG vaccination is effective in the prevention of TBM-associated mortality in childhood. TST negativity may be a sign of a poor prognosis in TBM cases.

Anti-basement membrane antibodies are now being associated with an increasing spectrum of disease, including Goodpasture's syndrome, rapidly progressive and occasionally milder forms of glomerulonephritis (GN), tubulointerstitial nephritis, pulmonary damage, and potentially other forms of tissue injury. We have developed a radioimmunoassay to detect circulating antiglomerular basement membrane (GBM) antibodies. The antigens for this assay are derived from the noncollagenous portion of the GBM remaining after collagenase digestion. After immunoabsorptive purification, the major antigens precipitated by human anti-GBM antibodies can be characterized by polyacrylamide gel electrophoresis (PAGE) into an unresolved high molecular weight fraction and two antigenic peaks of 54,000 and 27,000 daltons. The noncollagenous nature of the antigenic material has been confirmed by amino acid analysis. The radiolabelled antigen has proven useful in detecting circulating anti-GBM antibodies in over 500 patients. The assay is of use in monitoring the activity of disease and judging the patient's response to therapy. It is also useful in determining the timing of renal transplantation, if required. Differences in antigenic content of glomerular and tubular basement membranes (TBM) have been noted between individuals. These antigenic differences, under certain circumstances, can lead to the induction of anti-basement membrane antibody responses after transplantation.

Tubulointerstitial nephritis antigen (TIN antigen) is a basement membrane component which is recognized by human autoantibodies in TIN and has been shown to induce TIN in Brown Norway (BN) rats. Detectable by immunofluorescent microscopy, TIN antigen reacts with monoclonal, polyclonal, and human autoantibodies in basement membranes of kidney cortex, small intestine, skin and cornea. Specific sites of TIN antigen within kidney cortex include basement membranes of proximal tubules, distal tubules, Bowman's capsule and peritubular capillaries, with highest concentration in proximal tubular basement membrane (TBM). TIN antigen is also present in interstitium between tubules and in the periarterial sheath, but not in glomerular basement membrane or mesangial matrix. Immunoblotting of TIN antigen isolated from rabbit TBM reveals a major 58 kDa component with minor components of 300 kDa, 175 kDa, 160 kDa, 100 kDa and 50 kDa. Partial protein sequence analysis indicates that 58 kDa TIN antigen represents a newly defined glycoprotein. The structural relationships between various molecular weight forms are currently being investigated. High molecular weight (HMW) forms of TIN antigen, consisting of a mixture of 300 kDa, 175 kDa and 160 kDa forms, are more efficient than low molecular weight (LMW) forms (58 kDa and 50 kDa forms) in inducing TIN in BN rats. The resultant antibody specificity of rats injected with either HMW TIN antigen or LMW TIN antigen is identical as determined by immunofluorescent microscopy and Western analysis. Higher antibody titers and greater amounts of kidney-bound IgG are found in the HMW TIN antigen-immunized animals. TIN antigen is the primary target of anti-TBM antibodies in human and experimental immunologically-mediated anti-TBM nephritis.

Our previous studies showed that 54 kD and 48 kD tubular basement membrane (TBM) proteins were the major form of the target antigen involved in anti-TBM antibody-mediated tubulo-interstitial nephritis in humans. In those studies, we isolated the 54 kD glycoprotein (named gp54) from collagenase-digested bovine TBM. NH2-terminal amino acid sequencing indicated that gp54 represented a newly defined glycoprotein. In this study, we further characterized the target antigen, using mouse monoclonal antibodies to gp54 and polyclonal anti-gp54 peptide antibody. Two monoclonal antibodies (H79 and H80) were established, and they reacted, by immunofluorescence, predominantly with the proximal TBM of humans, rabbits, and Wistar, Sprague-Dawley, and Brown-Norway rats, but not with that of Lewis rats. They were also fixed by blotting intensely to the 54 kD component and weakly to the 48 kD component of collagenase-digested human TBM. In vivo transfer of H79 to Wistar rats showed extensive linear binding of mouse IgG to the TBM and the basal membrane of the small intestine; however, no pathologic changes were seen by light microscopy. The anti-gp54 peptide antibody reacted with both the 54 kD and 48 kD TBM components of human TBM. mRNA was prepared from rabbit kidneys, and fractionated to enrich mRNA encoding the 54 kD and 48 kD peptides. On in vitro translation experiments with the mRNA fraction, the 54 kD and 48 kD peptides were immunoprecipitated with anti-gp54 antibodies. These findings indicate that the 54 kD and 48 kD components are encoded with different mRNA, but that they share the same antigenic epitope.(ABSTRACT TRUNCATED AT 250 WORDS)

Tracheobronchomegaly (TBM) occasionally may progress to extensive tracheomalacia which leads to respiratory failure. Spirometry, dynamic expiratory multidetector computed tomography (CT), bronchoscopy are used to diagnose patients of suspected tracheobronchomalacia. We used the technique of night-time monitoring of respiratory variables to show the presence of respiratory abnormalities during sleep and which was corrected by applying nasal continuous positive airway pressure (CPAP). The study showed the presence of both apnoea and hypopnoeas, which were obstructive in nature with an apnoea-hypopnoea index (AHI) of 11, no snoring and associated oxygen desaturation of 75 per cent. A second overnight study with nasal continuous positive airway pressure at a critical pressure of 8 cm, the AHI decreased to 3 along with no drop in oxygen saturation. This non-invasive technique should be considered as a diagnostic tool in tracheobronchomalacia and to know the outcome of CPAP, surgical or stent therapy in this condition.

Voxel-based morphometry (VBM) and tensor-based morphometry (TBM) both rely on spatial normalization to a template and yet have different requirements for the level of registration accuracy. VBM requires only global alignment of brain structures, with limited degrees of freedom in transformation, whereas TBM performs best when the registration is highly deformable and can achieve higher registration accuracy. In addition, the registration accuracy varies over the whole brain, with higher accuracy typically observed in subcortical areas and lower accuracy seen in cortical areas. Hence, even the determinant of Jacobian of registration maps is spatially varying in their accuracy, and combining these with VBM by direct multiplication introduces errors in VBM maps where the registration is inaccurate. We propose a unified approach to combining these 2 morphometry methods that is motivated by these differing requirements for registration and our interest in harnessing the advantages of both. Our novel method uses local estimates of registration confidence to determine how to weight the influence of VBM- and TBM-like approaches. Results are shown on healthy and mild Alzheimer's subjects (N = 150) investigating age and group differences, and potential of differential diagnosis is shown on a set of Alzheimer's disease (N = 34) and frontotemporal dementia (N = 30) patients compared against controls (N = 14). These show that the group differences detected by our proposed approach are more descriptive than those detected from VBM, Jacobian-modulated VBM, and TBM separately, hence leveraging the advantages of both approaches in a unified framework.

The toad urinary bladder and epithelial cell lines derived from the urinary bladder, including TBM, serve as model systems for the study of transepithelial Na+ transport. We examined biochemical characteristics of epithelial Na+ channels in toad urinary bladder and TBM cells and their cellular localization in the urinary bladder. The radiolabeled amiloride analogue [3H]benzamil bound to a single class of high-affinity binding sites in membrane vesicles from toad urinary bladder with a dissociation constant (Kd) of 10 nM. Photoactive benzamil analogues specifically labeled a 135,000-Da polypeptide in toad urinary bladder and TBM cells. A monoclonal anti-Na+ channel antibody directed against the amiloride-binding component of the channel specifically recognized a 135,000-Da polypeptide in TBM cells. Polyclonal anti-Na+ channel antibodies generated against purified bovine epithelial Na+ channel specifically recognized a 235,000-Da polypeptide in toad urinary bladder and localized Na+ channels to the apical plasma membrane of urinary bladder epithelial cells. The biochemical characteristics and the cellular localization of epithelial Na+ channels in toad urinary bladder are similar to those previously described in mammalian kidney and in the A6 cell line.

Severe, diffuse tracheobronchomalacia (TBM) is an underrecognized cause of dyspnea, recurrent respiratory infections, cough, secretion retention, and even respiratory insufficiency. Patients often have comorbidities, such as asthma or chronic obstructive pulmonary disease, and inappropriate treatment for these conditions may precede eventual recognition of TBM by months or years. Most of these patients have an acquired form of TBM in which the etiology in unknown. Diagnosis of TBM is made by airway computed tomography scan and flexible bronchoscopy with forced expiration. The prevailing definition of TBM as a 50% reduction in cross-sectional area is nonspecific, with a high proportion of healthy volunteers meeting this threshold. The clinically significant threshold is complete or near-complete collapse of the airway. Airway stenting may treat TBM, although complications resulting from indwelling prostheses often limit the durability of stents. Surgical stabilization of the airway by posterior splinting (tracheobronchoplasty) effectively and permanently corrects malacic airways. Proper surgical selection is facilitated by a short-term stent trial.

BACKGROUND

Diagnosis of tuberculous meningitis (TBM) is a challenge because of the manifold clinical presentation, and diagnosis is often delayed.

OBJECTIVE

We wanted to share our experience of directly observed treatment short course (DOTS) in TBM. We did a retrospective analysis to look at the presentation, management and outcome of TBM patients from November 2006 to April 2008.

METHODS

TBM was diagnosed based on clinical criteria. We excluded patients with HIV.

RESULTS

We had 11 patients on DOTS regime. One died following hepatitis and another patient died of unrelated gastroenteritis. The only patient on daily regime died. Our patients generally presented late, at a median duration 20 days from onset of symptoms, and 50% had stage 3 disease at presentation. The median delay in diagnosis was 4.5 days.

CONCLUSIONS

We found DOTS to be effective in TBM but not without side effects.

Bovine glomerular basement membrane (GBM) was isolated and purified according to a modification of Spiro's method. Rat and bovine tubular basement membranes (TBM) were isolated and purified by sonic disruption or by the method of Carlson et al. Electron microscopic studies on the ultrastructure of GBM and TBM were performed after negative staining with 1% phosphotungstic acid solution, pH 7.3. When negatively stained, GBM and TBM were seen as fragments varying in size. The surface of the membranes showed a characteristic felt-like or spongy appearance. At higher magnification, GBM and TBM showed a fine meshwork composed of strands and pores which three-dimensionally resembled a crystal lattice. Pores were fairly uniform in size and shape. They were round, oval or polygonal in shape. Some of the pores were elongated to form short straight or bent channels. Strands were also uniform in diameter and surrounded a pore or channel. For an average of 50 pores, the long dimension was 3.1 +/- 0.6 nm and the short dimension 2.5 +/- 0.3 nm in bovine GBM, 3.8 +/- 1.2 and 2.5 +/- 0.7 nm in bovine TBM, and 4.9 +/- 1.5 and 2.8 +/- 0.6 nm in rat TBM, respectively. The strand was 1.8 +/- 0.3 nm in diameter in bovine GBM, 2.5 +/- 0.6 nm in bovine TBM and 3.7 +/- 0.7 nm in rat TBM for an average of 50 strands. The diameters of the pores were less than or close to the short axis of an albumin molecule. It was concluded that renal GBM and TBM were molecular sieves composed of pores and strands.