Traumatic brain injury (TBI) can cause widespread and prolonged brain degeneration. TBI can affect cognitive function and brain integrity for many years after injury, often with lasting effects in children, whose brains are still immature. Although TBI varies in how it affects different individuals, image analysis methods such as tensor-based morphometry (TBM) can reveal common areas of brain atrophy on magnetic resonance imaging (MRI), secondary effects of the initial injury, which will differ between subjects. Here we studied 36 pediatric moderate to severe TBI (msTBI) participants in the post-acute phase (1-6 months post-injury) and 18 msTBI participants who returned for their chronic assessment, along with well-matched controls at both time-points. Participants completed a battery of cognitive tests that we used to create a global cognitive performance score. Using TBM, we created three-dimensional (3D) maps of individual and group differences in regional brain volumes. At both the post-acute and chronic time-points, the greatest group differences were expansion of the lateral ventricles and reduction of the lingual gyrus in the TBI group. We found a number of smaller clusters of volume reduction in the cingulate gyrus, thalamus, and fusiform gyrus, and throughout the frontal, temporal, and parietal cortices. Additionally, we found extensive associations between our cognitive performance measure and regional brain volume. Our results indicate a pattern of atrophy still detectable 1-year post-injury, which may partially underlie the cognitive deficits frequently found in TBI.

We recently demonstrated that AMPK inhibition in spermatozoa regulates motility, plasma membrane organization, acrosome integrity and mitochondrial membrane potential. As AMPK activity varies in different energy conditions induced by sperm environment, this work investigates the functional effects of AMPK activation in boar spermatozoa. Spermatozoa were incubated under non-stimulating (TBM) or Ca(2+) and [Formula: see text]-stimulating (TCM) media in the presence/absence of AMPK activator, A769662, for different times. AMPK activity, evaluated as Thr(172) phosphorylation by western blot, is effectively increased by A769662 in spermatozoa. AMPK activation significantly reduces the percentage of motile spermatozoa under Ca(2+) and/or [Formula: see text]-stimulating conditions. Moreover, AMPK activation in spermatozoa incubated in TBM or TCM significantly reduces curvilinear VCL, straight-line VSL and average VAP velocities, which subsequently lead to a significant decrease in the percentage of rapid spermatozoa (VAP>> 80 μm/s). The effect of AMPK activation on motility is intensified by the absence of BSA in the incubation medium. AMPK activation for a short time prevents the decline in cell viability and in the sperm population displaying high mitochondrial membrane potential which is induced by Ca(2+) and [Formula: see text]. Sustained (24 h) AMPK activation under TBM or TCM significantly increases both lipid disorganization and phosphatidylserine externalization in the sperm plasma membrane, and diminishes the acrosome membrane integrity. In summary, AMPK activation modifies essential sperm processes such as motility, viability, mitochondrial membrane potential, acrosome membrane integrity, and organization and fluidity of plasma membrane. As these spermatozoa processes are required under different environmental conditions when transiting through the female reproductive tract to achieve fertilization, we conclude that balanced levels of AMPK activity are essential for regulating sperm function.

The target of autoantibodies in Goodpasture's disease, the Goodpasture antigen has recently been characterized as the NC1 domain of the alpha 3 chain of type IV collagen. In order to study the Goodpasture antigen in different organs, NC1 domains were isolated from basement membranes (BM) of human glomeruli (GBM), tubules (TBM), alveoli (ABM), placenta (PBM) and aorta (VBM). NC1 preparations were separated by 2-D electrophoresis, and silver stained or immunoblotted to determine the subunit structure and antigenicity of different basement membranes. All basement membranes contained monomeric components of MW 26 kDa and 24 kDa, and associated dimers, corresponding to the 2-D location of alpha 1(IV) and alpha 2(IV) chains respectively. However, GBM, ABM, and to a lesser extent TBM possessed an extra set of monomeric components of MW 28 kDa and associated dimers corresponding to the proposed location of alpha 3 (IV) and alpha 4 (IV) chains. 2-D-separated polypeptides were Western blotted with autoantibodies from patients with Goodpasture's disease, a monoclonal antibody to the Goodpasture antigen (P1) and a monoclonal antibody to the bovine alpha 3 (IV) chain. The predominant binding of all these reagents was to cationic 28 kDa monomers of GBM, ABM and TBM, corresponding to the alpha 3 (IV) chain, although autoantibodies and Pl also bound to neutral 28 kDa monomers, corresponding to the alpha 4 (IV) chain. Autoantibodies bound weakly to more neutral components of PBM and VBM, but neither monoclonal antibody bound to these basement membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

Cold-insoluble globulin was detected in both trophoblast and alveolar basement membrane preparations, whereas it was not detected in GBM preparations. Acidic structural glycoproteins from both placental villi and lung parenchyma, which were extracted with 0.3 M acetic acid and recovered by adjusting the pH to 4.7, also contained CIg. Fractions of TBM, solubilized by either dilute alkali (0.01 N NaOH), by reduction and alkylation of the disulfide bonds, or by 0.3 M acetic acid extraction, all contained the antigen and possessed properties similar to those of ASG. The ASG fractions also reacted with antifibrinogen, but proof that the two types of determinants occur on a given molecular species is lacking at present. Purified collagenase solubilized CIg from ABM, from lung parenchyma, and from the stroma of placental villi, and this finding is strong evidence for an association of CIg with collagen in these connective tissues.

The purpose of this study was to determine whether nitric oxide (NO) production by different mammary tumor cell lines correlated with their sensitivity to NO mediated injury. Three mammary tumor cell lines LM2, LM3 and LMM3 syngeneic to BALB/c mice were cultured in vitro with IFNgamma + LPS. Different levels of NO production among the three lines were detected in culture supernatants. The only tumor cell line which did not produce NO (LM2) showed the highest sensitivity to SNP-derived NO cytotoxicity (87%), while LM3 and LMM3 which both produced higher levels of NO than LM2, showed lower cytotoxicity by SNP (39% and 22% respectively). Spleen cells (SC) from M2 tumor bearing mice (TBM) were able to lyse LM2 cells by NO-dependent mechanisms. SC from M3-TBM exerted cytotoxicity against LM3 cells mainly by NO-independent mechanisms. Thus, we postulate an inverse correlation between NO production and NO mediated cytotoxicity in the three mammary tumor cell lines. It is possible that tumor cells producing NO develop mechanisms to resist NO injury.

Multisubject statistical analyses of diffusion tensor images in regions of specific white matter tracts have commonly measured only the mean value of a scalar invariant such as the fractional anisotropy (FA), ignoring the spatial variation of FA along the length of fiber tracts. We propose to instead perform tract-based morphometry (TBM), or the statistical analysis of diffusion MRI data in an anatomical tract-based coordinate system. We present a method for automatic generation of white matter tract arc length parameterizations, based on learning a fiber bundle model from tractography from multiple subjects. Our tract-based coordinate system enables TBM for the detection of white matter differences in groups of subjects. We present example TBM results from a study of interhemispheric differences in FA.

Human health risks from cyanobacterial blooms are primarily related to cyanotoxins that some cyanobacteria produce. Not all species of cyanobacteria can produce toxins. Those that do often do not produce toxins at levels harmful to human health. Monitoring programs that use identification of cyanobacteria genus and species and enumeration of cyanobacterial cells as a surrogate for cyanotoxin presence can overestimate risk and lead to unnecessary health advisories. In the absence of federal criteria for cyanotoxins in recreational water, the Oregon Health Authority (OHA) developed guideline values for the four most common cyanotoxins in Oregon's fresh waters (anatoxin-a, cylindrospermopsin, microcystins, and saxitoxins). OHA developed three guideline values for each of the cyanotoxins found in Oregon. Each of the guideline values is for a specific use of cyanobacteria-affected water: drinking water, human recreational exposure and dog recreational exposure. Having cyanotoxin guidelines allows OHA to promote toxin-based monitoring (TBM) programs, which reduce the number of health advisories and focus advisories on times and places where actual, rather than potential, risks to health exist. TBM allows OHA to more efficiently protect public health while reducing burdens on local economies that depend on water recreation-related tourism.

The early effects (1-4 h) of aldosterone on membrane conductance were studied in the TBM cells, an epithelial cell line derived from the toad urinary bladder. Aldosterone stimulated Na+ transport (measured as short-circuit current) and induced parallel increases of the amiloride-sensitive apical membrane Na+ conductance and the basolateral membrane conductance. In another set of experiments, we prevented the aldosterone-induced increase of the Na+ transport by adding amiloride to the apical solution in concentrations sufficient to reduce short-circuit current to values similar to that of matched control. The effect of aldosterone on the basolateral conductance was not inhibited. This effect was essentially due to a change of the barium-sensitive K(+)-specific conductance. We also observed that aldosterone prevented a time-dependent decline of the paracellular resistance observed in control preparations. Aldosterone induces an early increase of the basolateral membrane conductance, an effect that is not secondary to the increase of the Na+ load to the cell.

It has been demonstrated immunohistologically using cryostat sections that the lectins PHA and Con A bind to human placentae. Both lectins stain trophoblastic basement membrane (TBM), perivascular tissue and stroma. No staining of trophoblasts was observed. It has been shown by blocking experiments that the lectin binding sites on placental TBM are glycoproteins, whereas experiments involving pretreatment of placental sections with anti-collagen antisera or highly purified bacterial collagenase have indicated that lectin binding to stromal and perivascular structures is collagen-associated. The possible relation of TBM lectin-binding sites to immune response gene products is briefly discussed.

DNA replication origins of eukaryotes lack linear replicator elements but contain short (dT)(n) (dA)(n) sequences that could build mutually equivalent unorthodox structures. Here we report that the lamin B2 origin of DNA replication adopts an alternative form characterized by unpaired regions CTTTTTTTTTTCC/GGAAAAAAAAAAG (3900-3912) and CCTTTTTTTTC/GAAAAAAAAGG (4141-4151). Both unpaired regions are resistant to DNase and except in central parts of their homopyrimidine strands are sensitive to single strand-specific chemicals. Interactions that protect central pyrimidines probably stabilize the bubble-like areas. Because DNA fragments containing either one or both bubbles migrate in TBM (89 mm Tris base, 89 mm boric acid, and 2 mm MgCl(2)) PAGE even faster than expected from their linear size, interacting regions are expected to belong to the same molecule. In an origin fragment containing a single bubble, free homopyrimidine strand can only interact with Hoogsteen hydrogen bonding surfaces from a complementary double stranded sequence. Indeed, this origin fragment reacts with triplex preferring antibody. In competition binding experiments control double stranded DNA or single stranded (dT)(40) do not affect origin-antibody interaction, whereas TAT and GGC triplexes exert competitive effect. Because the chosen fragment does not contain potential GGC forming sequences, these experiments confirm that the lamin B2 origin adopts a structure partly composed of intramolecular TAT triads.

BACKGROUND

An investigation of the free radical scavenger sodium 2-sulfophenyl-N-tert-butyl nitrone (S-PBN) and the weak vasodilatator Tris buffer mixture (TBM) on cerebral cortical blood flow (CCBF) and the jugular bulb concentration of two eicosanoids, indicators of oxidative stress and inflammation, was undertaken in 30 anaesthetized piglets during cardiopulmonary resuscitation (CPR) and after restoration of spontaneous circulation (ROSC).

METHODS

Thirty animals were subjected to 8 min of untreated circulatory arrest followed by 8 min of closed-chest CPR. During CPR, the animals were randomized to receive 60 mg/kg S-PBN, 1 mmol/kg TBM or 2 ml/kg normal saline (n = 10 in each group). Systemic haemodynamic variables, CCBF and jugular bulb plasma concentrations of 8-iso-PGF2alpha and 15-keto-dihydro-PGF2alpha were measured.

RESULTS

The CCBF during reperfusion after ROSC was greater in the TBM group than in the S-PBN group, the regression coefficient between CCBF and mean arterial blood pressure being lower in the S-PBN group than in the TBM group. The jugular bulb plasma concentration of 8-iso-PGF2alpha during the first 30 min after ROSC was greater in the TBM group than in the S-PBN group. Administration of TBM after vasopressin did not attenuate the pressor effect of vasopressin.

CONCLUSIONS

Administration of S-PBN during CPR results in less cerebral oxidative stress, possibly by promoting normal distribution of cerebral blood flow.

Thickening of the tubular basement membrane (TBM) occurs in diabetic nephropathy, but the effects of high glucose on the functional aspects of proximal tubular epithelial cells are not clearly understood. In the present study, we examined the effects of elevated glucose concentrations on (a) integrin expression by human proximal tubular epithelial cells (HK-2) and integrin-mediated interactions with type IV collagen (colIV) and laminin, major components of TBM; (b) the expression of matrixins/matrix metalloproteinases (MMPs), which is regulated by integrins; and (c) the expression of tissue inhibitors of metalloproteinases (TIMPs). HK-2 cells cultured in 25 mM glucose underwent a reduction of the expression of alpha3, beta1, alpha(v)beta3, and alpha5 integrin subunits, with a concomitant increase of the alpha2 subunit, compared with cells grown in 5 mM glucose. Adhesion experiments demonstrated that high glucose led to increased cell adhesion on either colIV or laminin. Experiments of competition of adhesion using anti-integrin antibodies indicated that HK-2 cells in 5 mM glucose used mainly alpha(v)beta3 and alpha5beta1 integrins to adhere to colIV, whereas in 25 mM glucose they additionally used alpha2beta1. In the case of laminin, a beta1-mediated adhesion was observed when HK-2 cells were in 5 mM glucose, whereas in 25 mM glucose, alpha2beta1 and alpha(v)beta3 were also involved. Elevated glucose concentrations resulted in decreased expression of MMP-9 and MMP-2, whereas an increase in TIMP-1 and a decrease in TIMP-2 expression were observed. We also examined which integrins mediated the expression and secretion of matrixins MMP-2 and MMP-9. Ligation of alpha3beta1 with mAbs resulted in induction of MMP-2 expression and secretion, whereas antibody ligation of alpha(v)beta3 led to down-regulation of MMP-9. The above data implicate integrins of proximal tubular epithelial cells in the regulation of MMPs and in the development of TBM thickening in diabetic nephropathy.

Although tingible body macrophages (TBM) have been recognized in germinal centers for over 100 years, their role in the germinal center response is not clear. In this study, the kinetics of the TBM response was quantitatively assessed and correlated with the kinetics of germinal center development in young mice. The TBM response in old mice (which have an age-related depression of germinal center development; Szakal et al., 1990) was analyzed for comparison. Young and old immune mice were challenged with human serum albumin and 0, 1, 3, 5, 7, 10, and 14 days later the popliteal and axillary lymph nodes were evaluated. Germinal centers were localized histochemically in alternate serial sections using horseradish peroxidase conjugated peanut agglutinin. TBM numbers were determined per germinal center on adjacent sections by the presence of tingible bodies or histochemically by using the monoclonal antibody Mac-2. Analysis of lymph nodes from young mice showed that TBM numbers decreased with the dissociation of preexisting germinal centers. TBM reappeared 5 days after challenge and the TBM kinetics paralleled the increase in size of de novo germinal centers. In fact, a constant ratio of one TBM to every 350-450 B cells was maintained from day 5 to day 10. In old lymph nodes, TBM were generally absent throughout germinal center development. The lack of TBM prior to germinal center development and their absence in aged mice are inconsistent with the concept that TBM are required for the induction of the germinal center reaction. However, the data are consistent with a role for TBM in regulating the magnitude of the germinal center reaction.

Tuberculous meningitis (TBM) remains the most common form of neurotuberculosis in children. Four hundred and five cases of tuberculous meningitis (ages 3-156 months) seen at the Philippine Children's Medical Center (PCMC) from 1987 to 1998 were reviewed. Inclusion criteria include clinical and laboratory profile of TBM with pertinent evidence on imaging such as computed tomography and/or cranial sonography or histologic evidence of TBM. Nearly half of the cases were below age 2. The most common neurologic findings were altered sensorium, neck rigidity, motor and cranial deficits. The mortality rate was 16%. The neuropathologic findings in 31 autopsied cases were basal exudates in 100%, hydrocephalus in 71%, caseation necrosis in 68%, and 35% with infarcts. The most important determinant of outcome is the stage of illness at which the diagnosis is made and appropriate treatment is given. Although computed tomography was more definitive, cranial sonography was a very useful diagnostic tool considering the frequent occurrence below age 2. A short course (6 months) anti-tuberculous therapy for neurotuberculosis was shown to be adequate; shunting of cases with hydrocephalus did not show definite benefit.

Fifteen patients aged 31-74 years (five male, ten female) on renal biopsy showed intense linear deposits of light chains along tubular basement membranes (TBM) by immunofluorescence, and/or granular dense deposits on electronmicroscopy. Multiple myeloma was diagnosed in ten patients. The onset of myeloma and nephropathy was simultaneous in six patients; nephropathy preceded or followed the diagnosis of myeloma in three and one patients respectively. The mode of onset of nephropathy was acute or rapidly progressive renal failure in five cases, chronic renal failure in seven, and heavy proteinuria in three. Only two patients had normal renal function at biopsy. Serum monoclonal component was kappa in five patients, IgG kappa in three, IgD kappa in one, IgG lambda in one, IgA lambda in one, absent in three, and not detected in one. On light microscopy eight cases had nodular glomerulosclerosis, three cast nephropathy and 14 TBM thickening. Immunofluorescence for monoclonal light chain(s) was positive in 11 of 13 cases. Electron microscopy showed finely granular deposits in the inner side of glomerular basement membranes (GBM) and the outer side of TBM in 11 of 11 tested cases. The evolution was towards chronic renal failure in 12 patients (six of whom required dialysis), death in two, unknown in one. Four patients died after a period of dialysis, from infections or cardiovascular complications.

Heparan sulfate proteoglycan (HSPG) was extracted from human tubular basement membrane (TBM) with guanidine and purified by ion-exchange chromatography and gel filtration. The glycoconjugate was sensitive to heparitinase and resistant to chondroitinase ABC, had an apparent molecular mass of 200-400 kDa and consisted of 70% protein and 30% glycosaminoglycan. The amino acid composition was characterized by its high content of glycine, proline, alanine and glutamic acid. Hydrolysis with trifluoromethanesulfonic acid yielded core proteins of 160 and 110 kDa. The heparan sulfate (HS) chains obtained after alkaline NaBH4 treatment had a molecular mass of about 18 kDa. Results of heparitinase digestion and HNO2 treatment suggest a clustering of sulfate groups in the distal portion of the HS side chains. These chemical data are comparable to those obtained previously on glomerular basement membrane (GBM) HSPG (Van den Heuvel et al. (1989) Biochem. J. 264, 457-465). Peptide patterns obtained after trypsin, clostripain or V8 protease digestion of TBM and GBM HSPG preparations showed a large similarity. Polyclonal antisera and a panel of monoclonal antibodies raised against both HSPG preparations and directed against the core protein showed complete cross-reactivity in ELISA and on Western blots. They stained all basement membranes in an intense linear fashion in indirect immunofluorescence studies on human kidneys. Based on these biochemical and immunological data we conclude that HSPGs from human GBM and TBM are identical, or at least very closely related, proteins.

Although it is believed that in the western countries tuberculosis is a disease confined to high-risk groups such as immigrants, we describe four cases of tuberculous meningitis (TBM) in native Dutch children. The inverse relation between the delay in starting therapy and the clinical outcome makes early diagnosis of TBM essential. The often non-specific presenting symptoms and laboratory results, the time-consuming character of cultures and the unfamiliarity of western medical staff with the disease all may contribute to a delay in diagnosis of TBM. We believe that especially gadolinium-enhanced MRI or contrast-enhanced CT can be very helpful in the early diagnosis. Although not specific, hydrocephalus and basal meningeal enhancement on MRI or CT, together with the clinical suspicion can suggest the diagnosis to such an extent that there is enough reason to start antituberculous treatment.

The present study was designed to investigate Rv2623 antigen, a major dormancy regulon protein of Mycobacterium tuberculosis (MTB) in CSF of suspected latent and active tuberculous meningitis (TBM) patients. A total of 100 CSF samples from TBM (n = 31), suspected latent TBM (n = 22), and suitable noninfectious control subjects (n = 47) were collected and evaluated for Rv2623 antigen level using ELISA protocol. A significantly high (P < 0.05) mean absorbance was observed in samples of suspected latent TBM and active TBM patients as compared to non-TBM control patients. However, no significant difference in Rv2623 level was observed between suspected latent TBM and TBM patients. Our preliminary findings suggest that Rv2623 may be useful as a potential biomarker for the diagnosis of the latent as well as active TBM infection. Futher evaluation of this biomarker in large number of samples is therefore needed to confirm the result.

A retrospective study was done to correlate culture of Mycobacterium tuberculosis and detection of mycobacterial antigen in cerebrospinal fluid (CSF) by an inhibition enzyme-linked immunosorbent assay (ELISA). M. tuberculosis was cultured from CSF of 14 out of 70 patients with a clinical diagnosis of tuberculous meningitis (TBM). Mycobacterial antigens were demonstrated in CSF specimens by inhibition ELISA in all 14 culture-positive patients with antigen concentrations of 14.5-295 ng/ml (mean 158.8 ng/ml). Thus there was positive correlation between the detection of mycobacterial antigen and isolation of M. tuberculosis. Based on this observation, 56 CSF specimens from culture-negative patients with clinically diagnosed TBM were examined for mycobacterial antigen and the data were compared with those from culture positive patients. ELISA gave positive results in 38 specimens, with antigen levels of 12.5-280 ng/ml (mean 152.6 ng/ml). In 70 CSF specimens from patients with non-tuberculous neurological disease (control group), ELISA results were negative. Thus, detection of mycobacterial antigen in CSF specimens by inhibition ELISA had a specificity of 100% and a sensitivity of 67.8% for the diagnosis of TBM and is of potential value in the laboratory diagnosis of TBM.

Tuberculous meningitis (TBM) remains a common serious neurological emergency especially in the developing world. Elevated intracranial pressure (ICP) is often a feature of severe TBM and is associated with high morbidity and mortality. The pathology associated with TBM, such as cerebral edema, hydrocephalus, tuberculoma(s), and infarcts related to arthritis, contribute to increase in intracranial volume and, therefore, elevated ICP. The three types of edema (vasogenic, cytotoxic, and interstitial) may contribute to cerebral edema. The molecular mechanisms underlying the events that ultimately lead to brain damage and cerebral edema during infection are complex. Similarly to bacterial meningitis, cerebral blood flow autoregulation is probably impaired in TBM, and the mechanisms are unclear. Although no universal guidelines are available to institute ICP monitoring in patients with severe TBM, it is be prudent to monitor patients at risk for increases in ICP. Such an approach helps to detect the secondary brain insults, allowing for a more informed approach to treatment. Treatment of elevated ICP involves a multipronged approach. The first step should be to identify focal brain lesions and hydrocephalus (which require surgical intervention) by brain imaging. Cerebral edema is treated with hyperosmolar agents. Mannitol is currently the most commonly used agent. It appears that use of hypertonic saline as an osmotic agent in infection-related cerebral edema has certain advantages. However, this needs to be established by well-designed trials. Use of steroids reduces not only cerebral edema but also the production of cytokines and other chemicals involved in the immunopathogenesis of TBM. Fever associated with TBM should be aggressively treated, because fever can worsen the impact of elevated ICP. Hyponatremia may complicate TBM and requires appropriate correction because it can aggravate cerebral edema.

Membranous glomerulopathy (MGN) is characterized by subepithelial immune complex deposits and glomerular basement membrane (GBM) thickening. The majority of patients present with nephrotic syndrome and outcomes are variable. Pathologically, deposits at sites other than the subepithelial aspect of the GBM favor the presence of secondary forms of MGN which are seen most commonly in the setting of autoimmune disease, infection, neoplasia, and with certain therapeutic agents. MGN is the most common form of de novo glomerular disease seen in the renal allograft and may be seen concurrently with other forms of glomerular disease including focal segmental glomerulosclerosis, IgA nephropathy, diabetic nephropathy, and anti-TBM nephritis. This review emphasizes the detection of secondary forms and variants of MGN.

BACKGROUND

To assess the clinical profile, laboratory and neuroimaging data of adult tuberculous meningitis (TBM) patients and to determine the predictors of mortality.

METHODS

A total of 55 TBM patients and 60 controls were enrolled in this prospective study. Detailed clinical, radiological, biochemical and microbiological evaluation was performed.

METHODS

Done using SPSS 15.0 for Windows. P value of <0.05 was considered to be significant.

RESULTS

61.8% were males and majority of the study subjects belonged to age group of 21-40 years. Duration of symptoms in all cases was >14 days and commonly included fever, headache, neck rigidity, altered sensorium and vomiting. Biochemical features of cerebrospinal fluid (CSF) showed significant results where 94.5%, 85.45%,83.63% and 81.81% of patients showed CSF sugar levels <2/3 corresponding blood sugar, proteins>100mg%, CSF total leucocyte count of >20 cells/mm(3) and ADA >9.5IU/L respectively while neuroimaging revealed hydrocephalus, basal exudates and meningeal enhancement as significant findings. More than half of TBM patients presented in stage II of disease and overall mortality was 43.63%. A model for prediction of mortality in TBM cases was framed which included variables of age>40 years, past history of tuberculosis (TB), presence of basal exudates and hydrocephalus.

CONCLUSIONS

TBM is a serious extrapulmonary form of TB and should arise suspicion in mind of clinician based on clinical, laboratory and radiologic results. Further, a model for prediction of mortality in such patients may be helpful for early intervention and better prognosis.

BACKGROUND

Tuberculous meningitis (TBM), a tuberculous infection of the leptomeninges, carries significant morbidity and mortality. To date, little literature is available regarding TBM in Pakistan.

METHODS

All adult patients with TBM admitted to a tertiary care teaching hospital in Karachi, were reviewed retrospectively.

OBJECTIVE

To describe the demographic profile, clinical features, laboratory and radiological picture of these patients and to identify predictors of mortality.

RESULTS

Among the 190 patients analyzed, majority (28%) were between 21-30 years of age. Fever (90%), impaired consciousness (63%) and nausea/vomiting (50%) were the most common presenting symptoms. Thirty four percent were categorized as clinical stage III. CSF cultures were positive in only 5%. Thirty seven percent had an associated lung pathology on a chest X-ray. Neuroimaging revealed meningeal enhancement in 27% and hydrocephalus in 23%. All patients were treated with antituberculous therapy; 79% received concomitant steroid therapy. Neurosurgical intervention was required in 13% and mechanical ventilation support in 12%. Overall mortality was 20% and neurological sequelae were seen in 42% of the survivors. Univariate analysis showed age greater than sixty years, clinical stage III and mechanical ventilation as predictors of mortality. The logistic regression model, however, revealed that stage III presentation was not an independent predictor.

CONCLUSIONS

We continue to see late presentations of TBM in our setting. The current study has shown that age greater than sixty years and the need for mechanical ventilation are significant independent predictors of mortality.

BACKGROUND

Schizophrenia is associated with various brain structural abnormalities, including reduced volume of the hippocampi, prefrontal lobes and thalami. Cannabis use increases the risk of schizophrenia but reports of brain structural abnormalities in the cannabis-using population have not been consistent. We used automated image analysis to compare brain structural changes over time in people at elevated risk of schizophrenia for familial reasons who did and did not use cannabis.

METHODS

Magnetic resonance imaging (MRI) scans were obtained from subjects at high familial risk of schizophrenia at entry to the Edinburgh High Risk Study (EHRS) and approximately 2 years later. Differential grey matter (GM) loss in those exposed (n=23) and not exposed to cannabis (n=32) in the intervening period was compared using tensor-based morphometry (TBM).

RESULTS

Cannabis exposure was associated with significantly greater loss of right anterior hippocampal (pcorrected=0.029, t=3.88) and left superior frontal lobe GM (pcorrected=0.026, t=4.68). The former finding remained significant even after the exclusion of individuals who had used other drugs during the inter-scan interval.

CONCLUSIONS

Using an automated analysis of longitudinal data, we demonstrate an association between cannabis use and GM loss in currently well people at familial risk of developing schizophrenia. This observation may be important in understanding the link between cannabis exposure and the subsequent development of schizophrenia.