In order to characterize abnormalities in nephronophthisis, renal tissues from four patients were studied by light and electron microscopies and immunofluorescence using antibodies to laminin, type IV collagen, and tubular basement membranes (TBM). There were constant morphological alterations affecting TBM of all segments of the nephron, with or without cysts. These included extreme thinning and attenuation, layering, and thickening of these structures which ranged in size from 36 nm to 2000 nm. A combination of these features often affected the same TBM simultaneously, with abrupt transitions between different lesions. Although the ultrastructural TBM aberrations were observed in a wide variety of other chronic and acute renal disorders, they rarely occurred to the extent as in nephronophthisis or with abrupt transitions, both suggesting diagnostic significance. Laminin and type IV collagen were present in normal intensity and distribution, however, anti-TBM antibody staining was inconstantly reduced, perhaps signifying lack of a normal antigenic component in the TBM. These findings may well indicate the fundamental defect in nephronophthisis to be production of abnormal TBM, similar to the glomerular basement membrane lesions and consequences in Alport's syndrome.

BACKGROUND

The early diagnosis of tuberculous meningitis (TBM) is very crucial, since delayed diagnosis can lead to various neurological manifestations. We have previously developed an in-house indirect enzyme-linked immunosorbent assay (ELISA) for TBM diagnosis using the Antigen 85 (Ag 85) complex. It has been suggested that the Ag 85 complex might give false-positive reactions for individuals vaccinated with Bacillus Calmette-Guérin (BCG).

OBJECTIVE

In the present study, we describe a prospective evaluation demonstrating that early secreted antigenic target- 6 (ESAT-6), which is absent in Mycobacterium bovis BCG strains, is in the cerebrospinal fluid (CSF) of TBM patients.

METHODS

We used an indirect ELISA to detect ESAT-6 antigens in the CSF of TBM patients using polyclonal antibodies against ESAT-6.

RESULTS

Using the indirect ELISA method, we demonstrated a sensitivity and specificity of 80% and 94%, respectively, for the diagnosis of TBM.

CONCLUSIONS

The detection of ESAT-6 in the CSF of TBM patients by indirect ELISA is a promising method and can be used to develop an immunodiagnostic assay with increased sensitivity and specificity.

Twenty-seven patients with diffuse "crescentic" glomerulonephritis (CSGN) were identified in 1,174 renal biopsies from nephritic patients. Patients were assigned to three groups on the basis of the immunofluorescent study of renal biopsy specimens and serologic findings. Group I included eight patients with antibodies to glomerular (anti-GBM) and tubular (anti-TBM) basement membranes; group II had eight patients with only anti-GBM antibodies; and group III had eleven patients with CSGN unassociated with antibodies to either GBM or TBM. Patients with anti-GBM/anti-TBM antibodies (group I) had severe tubulointerstitial (TI) nephritis, as characterized by the infiltration of polymorphonuclear leukocytes and macrophages along the TBM and peritubular vessels. In some patients, focal proliferation of epithelial cells of proximal convoluted tubules (PCT), gaps or extensive destruction of TBM, lesions in the walls of small peritubular vessels, and interstitial giant cells were also observed. Patients with anti-GBM antibodies (group II) had mild to moderate interstitial cellular infiltration and mild tubular changes. Five patients with CSGN not associated with antibodies to renal basement membranes (group III) had mild to moderate interstitial cellular infiltration and tubular changes. A sixth patient, with Wegener's disease had severe granulomatous TI lesions. The results of this study show that TI nephritis is most frequent and severe with anti-TBM antibodies are demonstrable and suggest that anti-TBM antibodies contribute to the development of TI lesions.

All four human IgG subclasses, and both kappa and lambda light chains, were detected by immunofluorescence in similar distributions in chorionic villi of human placentae. IgG1 and IgG3 were the predominant subclasses. No evidence was obtained for local enzymatic digestion of IgG during placental transfer. Most of the IgG on the trophoblastic basement membrane (TBM) was loosely bound and could be removed by prolonged washing, although some appeared to be more tightly bound to small segments of the TBM. IgM, but not IgA, was present in small amounts in placental villous structures. Immunoglobulin was never observed within the syncytiotrophoblast. Antisera to IgG genetic (Gm) markers were used to locate IgG thought to be of foetal or maternal origin. The presence of paternal Gm markers not carried by the mother was taken as evidence for foetal IgG. Foetal (paternal) Gm markers were observed in placentae, although maternal IgG was the major immunoglobulin present in placental villi. Both maternal and foetal IgG were demonstrated in fibrinoid deposits, vessel walls and the cytoplasm of some stromal cells. Only foetal IgG was definitively observed in the immunoglobulin that is tightly bound to the TBM.

To investigate the maternal-fetal transfer of tobramycin (TBM) and its distribution in the fetus, a single dose of 2 mg/kg was administered intramuscularly to 35 pregnant patients (13 first trimester, 22 second trimester) 0.5 to 34 h before hysterectomy. TBM concentration was assayed microbiologically in maternal serum, fetal tissues (placenta, brain, lung, liver, and kidney), and fluids (amniotic, cerebrospinal fluid [CSF], urine, and serum). Mean maternal serum half-life (1.54 h) and mean peak serum concentration of TBM were within ranges reported for nonpregnant adults. In fetal serum, half-life was 5.2 h, and TBM levels did not exceed 0.58 mug/ml. For intervals up to 34 h, the mean TBM concentration in placental tissues was 1.4 mug/g. Concentration differences related to fetal maturation were found for fetal CSF, amniotic fluid, and fetal kidney. No antimicrobial activity was found in the fetal CSF of >16 weeks' gestation. TBM was present predominantly in the second trimester amniotic fluid specimens. Fetal kidney concentrations reached 7.2 mug/g at 34 h after maternal drug administration. Higher TBM concentrations were related to advanced maturation of the fetal kidney. Second trimester fetal urine concentrations for TBM ranged from 0.1 to 3.4 mug/ml, and the fetal urinary half-life was 3.7 h. Knowledge of fetal pharmacology is essential for weighing the fetal benefits or risks of antimicrobial therapy for the infected gravid patient.

Conventional aerosol delivery systems and the availability of new technologies have led to the development of "intelligent" nebulizers such as the I-neb Adaptive Aerosol Delivery (AAD) System. Based on the AAD technology, the I-neb AAD System has been designed to continuously adapt to changes in the patient's breathing pattern, and to pulse aerosol only during the inspiratory part of the breathing cycle. This eliminates waste of aerosol during exhalation, and creates a foundation for precise aerosol (dose) delivery. To facilitate the delivery of precise metered doses of aerosol to the patient, a unique metering chamber design has been developed. Through the vibrating mesh technology, the metering chamber design, and the AAD Disc function, the aerosol output rate and metered (delivered) dose can be tailored to the demands of the specific drug to be delivered. In the I-neb AAD System, aerosol delivery is guided through two algorithms, one for the Tidal Breathing Mode (TBM), and one for slow and deep inhalations, the Target Inhalation Mode (TIM). The aim of TIM is to reduce the treatment time by increasing the total inhalation time per minute, and to increase lung deposition by reducing impaction in the upper airways through slow and deep inhalations. A key feature of the AAD technology is the patient feedback mechanisms that are provided to guide the patient on delivery performance. These feedback signals, which include visual, audible, and tactile forms, are configured in a feedback cascade that leads to a high level of compliance with the use of the I-neb AAD System. The I-neb Insight and the Patient Logging System facilitate a further degree of sophistication to the feedback mechanisms, by providing information on long term adherence and compliance data. These can be assessed by patients and clinicians via a Web-based delivery of information in the form of customized graphical analyses.

BACKGROUND

Remodelling of matrix and tubular basement membranes (TBM) is a characteristic of polycystic kidney disease. We hypothesized that matrix and TBM degradation by metalloproteinases (MMPs) could promote cyst formation. We therefore investigated the renal expression of MMPs in the Han:SPRD rat model of autosomal dominant polycystic kidney disease (ADPKD) and examined the effect of sirolimus treatment on MMPs.

METHODS

5-week-old male heterozygous (Cy/+) and wild-type normal (+/+) rats were treated with sirolimus (2 mg/kg/day) through drinking water for 3 months.

RESULTS

The mRNA and protein levels of MMP-2 and MMP-14 were markedly increased in the kidneys of heterozygous Cy/+ animals compared to wild-type +/+ as shown by RT-PCR and Western blot analyses for MMP-2 and MMP-14, and by zymography for MMP-2. Strong MMP-2 expression was detected by immunoperoxidase staining in cystic epithelial cells that also displayed an altered, thickened TBM. Tissue inhibitor of metalloproteinases-2 (TIMP-2) expression was not changed in Cy/+ kidneys. Sirolimus treatment leads to decreased protein expression of MMP-2 and MMP-14 in Cy/+, whereas MMP-2 and MMP-14 mRNA levels and TIMP-2 protein levels were not affected by sirolimus.

CONCLUSIONS

In summary, in kidneys of the Han:SPRD rat model of ADPKD, there is a marked upregulation of MMP-2 and MMP-14. Sirolimus treatment was associated with a marked improvement of MMP-2 and MMP-14 overexpression, and this correlated also with less matrix and TBM alterations and milder cystic disease.

The objective of this study was to identify independent predictor factors for diagnosis of tuberculous meningitis and develop a clinical prediction tool based upon a set of simple clinical and laboratory parameters in our local population. Clinical and laboratory features were compared in 68 patients with tuberculous meningitis and 123 cases of acute bacterial meningitis in 3 referral centres for tuberculosis in south-eastern Iran. Twenty-two clinical and laboratory features were analysed. Based on the best-fitted model a receiver operating characteristic curve with the highest surface under the curve was constructed. Disease duration before diagnosis >>or=5 d) had the highest odds ratio of 21.9. Age over 30 y, CSF leukocyte count <or=1000 x 10(3) cells/ml and CSF lymphocytosis>>or=70% were placed after disease duration with odds ratios of 5.1, 3.7 and 2.6, respectively. Sensitivity, specificity and likelihood ratio for a positive test in this model were 84%, 88% and 7.4, respectively. The area under the ROC curve was 0.92. It appears that a single model can not predict <em>TBM</em> diagnosis in different populations. Using clinical and laboratory parameters may facilitate empirical diagnosis of <em>TBM</em> in endemically low income countries with limited microbiological diagnostic facilities.

Neurological damage, due to conditions such as stroke, results in a complex pattern of structural changes and significant behavioural dysfunctions; the automated analysis of magnetic resonance imaging (MRI) and discovery of structural-behavioural correlates associated with these disorders remains challenging. Voxel lesion symptom mapping (VLSM) has been used to associate behaviour with lesion location in MRI, but this analysis requires the definition of lesion masks on each subject and does not exploit the rich structural information in the images. Tensor-based morphometry (TBM) has been used to perform voxel-wise structural analyses over the entire brain; however, a combination of lesion hyper-intensities and subtle structural remodelling away from the lesion might confound the interpretation of TBM. In this study, we compared and contrasted these techniques in a rodent model of stroke (n=58) to assess the efficacy of these techniques in a challenging pre-clinical application. The results from the automated techniques were compared using manually derived region-of-interest measures of the lesion, cortex, striatum, ventricle and hippocampus, and considered against model power calculations. The automated TBM techniques successfully detect both lesion and non-lesion effects, consistent with manual measurements. These techniques do not require manual segmentation to the same extent as VLSM and should be considered part of the toolkit for the unbiased analysis of pre-clinical imaging-based studies.

Clinical and radiological changes in tuberculous meningitis (TBM) have been reported but there is paucity of comprehensive serial clinicoradiological follow-up. In this prospective hospital based study, we investigated serial changes in the clinical and radiological findings and their relationships over 6 months in 31 consecutive patients with TBM, diagnosed on the basis of clinical, radiological and spinal fluid criteria. We graded the severity of the TBM as I-III. Detailed clinical examination, contrast-enhanced CT and activities of daily living (ADL) assessments were made on admission, and 3 and 6 months after therapy. Further CT was carried out as required. Patients received four-drug antituberculous therapy (RHZE) and underwent a ventriculoperitoneal shunt if necessary. Outcome was defined as poor, partial or complete recovery using the Barthel index score at 6 months. The age of the patients was 6-80 years, mean 35.2 years; four were children and 13 female. Meningitis was stage I in 5, stage II in six and stage III in 20 patients. Focal weakness was present in nine, papilloedema in six and ophthalmoplegia in ten. There were ten patients who deteriorated within first 6 weeks of therapy. Mean Glasgow coma score (GCS) deteriorated from 12.5 to 11.4; the grade of meningitis increased by two stages in one patient, one stage in another, and motor deficits appeared in four and optic atrophy in four; four patients required shunt surgery. By 3 months most patients were stable. At 6 months 17 patients had complete, four partial and nine poor recovery. Initial CT was abnormal in 28 patients, revealing hydrocephalus and exudates in 15 each, infarcts in ten and tuberculomas in 13. It was repeated in ten patients who deteriorated, showing new abnormalities such as hydrocephalus in two, infarcts in four, exudates in four and granulomas in two, with worsening of the previous findings. CT at 3 and 6 months was still abnormal in most patients. At 6 months hydrocephalus had disappeared in four, as had tuberculomas in seven and exudates in six, but infarcts did not change. Initial deterioration was related to weakness on admission and the GCS. Cognitive impairment significantly correlated with exudates and tuberculomas and motor deficits with infarcts. Thus, a third of patients with TBM may deteriorate within 6 weeks of starting treatment and CT can be helpful in managing them. Worsening on treatment was related to weakness and GCS on admission. In most patients CT remained abnormal at 6 months despite clinical recovery.

Proximal straight tubules (S2 segments) swell rapidly in hypotonic media, but within a few minutes their volume returns toward control levels due to extrusion of K, Na, Cl, and water from the cytoplasm. In the present studies we determined the extent to which hydrostatic pressure (derived from the elastic tubule basement membrane (TBM) as the tubule enlarged in hypotonic medium) contributed to the regulation of cell volume. Removal of the TBM by collagenase had no effect on cell volume regulation in otherwise normal tubules. By contrast, tubules treated with ouabain, though they appeared to regulate their volumes in hypotonic media, were unable to do so in the presence of glycoside if the TBM had been removed with collagenase. This latter result is interpreted to show that hydrostatic pressure generated by extension of the TBM can cause "apparent" volume regulation when the sodium pump is blocked by ouabain. We conclude that normal proximal renal tubules regulate cell volume in hypotonic solutions by mechanisms that are dependent on the normal operation of the classical sodium pump.

Tracheobronchomalacia (TBM) is an important cause of airway distress during infancy, but it generally resolves as the airway enlarges. To assess the origin and natural history of TBM, a chart review and telephone survey were conducted for 50 patients with TBM at the Children's Hospital of Philadelphia (Pa). This study revealed that TBM is a relatively common airway abnormality and is found on 15% of all diagnostic bronchoscopies. Prematurity, low birth weight, bronchopulmonary dysplasia, and prolonged ventilation predispose patients to the most severe symptoms. In our study, a tracheotomy with continuous positive airway pressure was required by 75% of the premature infants and 25% of the full-term infants with TBM. Seventy-one percent of all patients underwent decannulation without any other surgical intervention and remained nearly asymptomatic. Some patients could not undergo decannulation because of other airway lesions. In most instances, TBM is a self-limited disease that resolves without surgery.

OBJECTIVE

To compare 3 immunoassays, an immune complex assay, and an application of the polymerase chain reaction (PCR) for the diagnosis of tuberculous meningitis (TBM).

METHODS

Cerebrospinal fluid (CSF) from 33 patients with TBM and from 34 control patients with infectious and non-infectious CNS diseases was analysed.

RESULTS

The antibody immunoassays were either nonspecific or insensitive. However, detection of mycobacterial IgG immune complexes correlated strongly with infection, as they were detected in the CSF from 64% of the patients with TBM compared to only 3 (9%) of the control samples. PCR analysis, using Mycobacterium tuberculosis-specific oligonucleotide primers, also strongly correlated with infection, as DNA was amplified from 54% of the samples from patients with TBM, but from only 2 (6%) of the control samples. Both 'false positive' samples were also positive in the immune complex assay and came from 2 patients with otogenic brain abscesses. It is conceivable that these patients suffered from otogenic tuberculosis with secondary non-mycobacterial meningitis. When combining the immune complex assay with DNA-detection by PCR, 100% of the culture positive and 74% of culture negative samples were found to be positive, while maintaining a high specificity.

CONCLUSIONS

Parallel analysis to detect mycobacterial immune complexes and M. tuberculosis-specific DNA by PCR from the CSF of patients may offer a sensitive and specific tool for the diagnosis of TBM.

Twenty patients of tuberculous meningitis (TBM) in age group of 6 months to 10 years included in the study were divided into two groups of 10 patients each. Rifampicin was administered in dosage of 10 mg and 7.5 mg/kg bw to each patient of groups I and II respectively. Drug concentrations in serum and CSF of these patients were measured by a microbiological tube dilution method using a strain of Sarcina lutea. In group I mean serum and CSF concentration was 3.84 micrograms/ml and 0.178 microgram/ml respectively, while in group II it was 2.16 micrograms/ml and 0.206 microgram/ml respectively. These concentrations were many times higher than the MIC against Mycobacterium tuberculosis. Mean percentage penetration of rifampicin in CSF was 5 and 10% in group I and II respectively. We recommend similar studies in large number of children before advocating the therapy with low dose of rifampicin in TBM.

In the template-based modeling (TBM) category of CASP10 experiment, we introduced a new protocol called protein modeling system (PMS) to generate accurate protein structures in terms of side-chains as well as backbone trace. In the new protocol, a global optimization algorithm, called conformational space annealing (CSA), is applied to the three layers of TBM procedure: multiple sequence-structure alignment, 3D chain building, and side-chain re-modeling. For 3D chain building, we developed a new energy function which includes new distance restraint terms of Lorentzian type (derived from multiple templates), and new energy terms that combine (physical) energy terms such as dynamic fragment assembly (DFA) energy, DFIRE statistical potential energy, hydrogen bonding term, etc. These physical energy terms are expected to guide the structure modeling especially for loop regions where no template structures are available. In addition, we developed a new quality assessment method based on random forest machine learning algorithm to screen templates, multiple alignments, and final models. For TBM targets of CASP10, we find that, due to the combination of three stages of CSA global optimizations and quality assessment, the modeling accuracy of PMS improves at each additional stage of the protocol. It is especially noteworthy that the side-chains of the final PMS models are far more accurate than the models in the intermediate steps.

We reported previously that vaccination of reconstituted, lymphopenic mice resulted in a higher frequency of tumor-specific effector T cells with therapeutic activity than vaccination of normal mice. Here, we show that lymphopenic mice reconstituted with spleen cells from tumor-bearing mice (TBM), a situation that resembles the clinical condition, failed to generate tumor-specific T cells with therapeutic efficacy. However, depletion of CD25(+) Treg from the spleen cells of TBM restored tumor-specific priming and therapeutic efficacy. Adding back TBM CD25(+) Treg to CD25(-) naïve and TBM donor T cells prior to reconstitution confirmed their suppressive role. CD25(+) Treg from TBM prevented priming of tumor-specific T cells since subsequent depletion of CD4(+) T cells did not restore therapeutic efficacy. This effect may not be antigen-specific as three histologically distinct tumors generated CD25(+) Treg that could suppress the T-cell immune response to a melanoma vaccine. Importantly, since ex vivo depletion of CD25(+) Treg from TBM spleen cells prior to reconstitution and vaccination fully restored the generation of therapeutic effector T cells, even in animals with established tumor burden, we have initiated a translational clinical trial of this strategy in patients with metastatic melanoma.

BACKGROUND

We analyzed the gammadelta T cell composition and responses in the peripheral blood and cerebrospinal fluid (CSF) of children affected by tuberculous meningitis (TBM) and in control children.

METHODS

Peripheral blood and CSF samples were stimulated with different phosphoantigens and IL-2, and expansion of Vgamma9/Vdelta2 T cells assessed by FACS analysis. Vgamma9/Vdelta2 lines were obtained by culturing CSF or peripheral blood mononuclear cells (PBMC) in vitro with phosphoantigens and IL-2 for 2 months, and tested for proliferation and cytokine production in response to phosphoantigens. Vdelta2(D)Jdelta junctional sequence length was assessed by PCR.

RESULTS

The repertoire of gammadelta T cells from the CSF of TBM patients was characterized by the predominance of Vgamma9/Vdelta2 T lymphocytes, which accounted for >80% of gammadelta T cells. Vgamma9/Vdelta2 cells from the CSF of TBM children responded to different synthetic and natural (mycobacterial) phosphoantigens and produced discrete amounts of IFN-gamma and TNF-alpha. The in vitro expansion of Vgamma9/Vdelta2 T cells from CSF and peripheral blood of TBM patients prominently decreased following chemotherapy, and similarly, the proportion of ex vivo unstimulated Vgamma9/Vdelta2 T cells in CSF of TBM patients decreased to levels detected in the CSF of control subjects. Vdelta2 CDR3 TCR analysis showed that the remaining Vdelta2 cells in the CSF of TBM patients were still polyclonal.

CONCLUSIONS

These findings are consistent with an involvement of Vgamma9/Vdelta2 T cells in TBM. http://link. springer-ny.com/link/service/journals/00020/bibs/5n5p301. html

Exposure of rabbit pulmonary vascular smooth muscle cells to H2O2 dose-dependently stimulates the cell membrane associated protein kinase C (PKC) activity, phospholipase A2 (PLA2) activity, phospholipase A2 (PLA2) activity, and arachidonic acid (AA0) release. Pretreatment of the cells with staurosporine (an inhibitor of PKC) prevents AA release and PLA2 activity caused by H2O2. Treatment of the cells with 4 beta-PMA (an active phorbol ester), or 4 alpha-PMA (an inactive phorbol ester) does not affect basal AA release. In contrast, 4 beta-PMA significantly stimulates the cell membrane associated PKC activity. Treatment of the cells with 4 beta-PMA for a short time (up-regulation of PKC) augments PLA2 activity and AA release caused by a sub-optimal dose of H2O2 (0.4 mM). Under this condition, staurosporine prevents the stimulatory effects of 4 beta-PMA on membrane PLA2 activity, and AA release. In contrast to the up-regulation, pretreatment with 4 beta-PMA for a longer time (down-regulation of PKC) does not appreciably augment PLA2 activity and AA release caused by 0.4 mM H2O2. Treatment of the cells with an intracellular Ca2+ antagonist TBM-8 prevents H2O2 induced membrane PLA2 activity and AA release without affecting membrane PKC activity. Treatment of the cells with TMB-8 before addition of 4 beta-PMA (up-regulation of PKC) followed by incubation with 0.4 mM H2O2 does not augment PLA2 activity and AA release, although membrane PKC activity increases under this condition.

BACKGROUND

In India, tuberculous meningitis (TBM) is still a major cause of neurological disabilities and death.

OBJECTIVE

To identify the clinical variables which predict the outcome in childhood TBM.

METHODS

Tertiary teaching hospital.

METHODS

Prospective observational study.

METHODS

Thirty-six clinical variables were analyzed in 123 consecutive children with TBM admitted between May 2000 and August 2003. The outcome was assessed in terms of survival or death. Survival meant that the patient was discharged from hospital having made a complete recovery, or with disability.

RESULTS

Twenty-five (20%) children recovered completely, 70 (57%) survived with disability, and 28 (23%) died. Employing univariate analysis nine variables correlated with survival with disability outcome: presence of tonic motor posturing, cranial nerve palsy, focal neurological deficit, hypertonia, moderate to severe hydrocephalus, cerebral infarction on cranial CT, and requiring shunt surgery, and absence of extracranial tuberculosis and no antituberculous-related hepatotoxicity; two variables correlated with fatal outcome: presence of deep coma (Glasgow coma scale score P = 0.012, d.f. = 1, OR 0.12, 95% CI 0.02-0.62) correlated with survival with disability outcome, and presence of deep coma (P = 0.030, d.f. = 1, OR 0.35, 95% CI 0.14-0.90) with fatal outcome.

CONCLUSIONS

In children with TBM, the presence of hypertonia at admission is an independent predictor of neurological sequelae in survivors, and deep coma is an independent predictor of mortality.

Fractures of the proximal femur are the most devastating outcome of osteoporosis. It is generally understood that age-related changes in hip structure confer increased risk, but there have been few explicit comparisons of such changes in healthy subjects to those with hip fracture. In this study, we used quantitative computed tomography and tensor-based morphometry (TBM) to identify three-dimensional internal structural patterns of the proximal femur associated with age and with incident hip fracture. A population-based cohort of 349 women representing a broad age range (21-97years) was included in this study, along with a cohort of 222 older women (mean age 79±7years) with (n=74) and without (n=148) incident hip fracture. Images were spatially normalized to a standardized space, and age- and fracture-specific morphometric features were identified based on statistical maps of shape features described as local changes of bone volume. Morphometric features were visualized as maps of local contractions and expansions, and significance was displayed as Student's t-test statistical maps. Significant age-related changes included local expansions of regions low in volumetric bone mineral density (vBMD) and local contractions of regions high in vBMD. Some significant fracture-related features resembled an accentuated aging process, including local expansion of the superior aspect of the trabecular bone compartment in the femoral neck, with contraction of the adjoining cortical bone. However, other features were observed only in the comparison of hip fracture subjects with age-matched controls including focal contractions of the cortical bone at the superior aspect of the femoral neck, the lateral cortical bone just inferior to the greater trochanter, and the anterior intertrochanteric region. Results of this study support the idea that the spatial distribution of morphometric features is relevant to age-related changes in bone and independent to fracture risk. In women, the identification by TBM of fracture-specific morphometric alterations of the proximal femur, in conjunction with vBMD and clinical risk factors, may improve hip fracture prediction.

Spinal arachnoiditis is one of the common and disabling complication of tuberculous meningitis (TBM). We focused on early diagnosis of spinal arachnoiditis by spinal MRI in asymptomatic patients in whom neurological examination was normal. We studied 16 patients with a diagnosis of probable or highly probable TBM with symptoms for less than 1 month; three had radiological evidence of spinal arachnoiditis. High cerebrospinal fluid protein appeared to be a risk factor for development of spinal arachnoiditis. MRI is sensitive to detect early spinal arachnoiditis. Earlier diagnosis may be helpful in management of spinal arachnoiditis in TBM.

BACKGROUND

Tuberculous meningitis (TBM) is a major global health problem, and it is sometimes difficult to perform a differential diagnosis of this disease from other diseases, particularly partially-treated pyogenic meningitis (PTPM). In an earlier study, we demonstrated the presence of a 30-kD protein antigen in cerebrospinal fluid (CSF) of TBM patients. We have also shown that lymphocytes from CSF of TBM patients respond differently to this antigen than do those from PTPM patients. The purpose of this study was to develop an assay that can discriminate between TBM and PTPM.

METHODS

We developed a cell enzyme-linked immunosorbant assay (Cell ELISA) to quantitatively measure production of antibodies against the 30-kD protein in B cells from CSF of TBM and PTPM patients.

RESULTS

The cell ELISA yielded 92% (11/12) sensitivity and 92% (11/12) specificity for the differential diagnosis of TBM from PTPM.

CONCLUSIONS

When induced with the 30-kD protein antigen, B cells derived from CSF of TBM patients respond to IgG production within 24 h while those derived from PTPM patients do not respond.

The concentration of albumin was measured by a double-antibody radioimmunoassay in the glomerular basement membrane (GBM) and tubular basement membrane (TBM) of patients with diabetic nephropathy, other kidney diseases, and normal kidneys. The TBM from diabetics contained significantly more albumin (m +/ SD; 2.75 +/- 0.34 microgram/mg) than the TBM from other diseases (1.00 +/- 0.24 microgram/mg) or normals (1.21 +/- 0.26 microgram/mg) (P less than 0.0001). Similarly, diabetic GBM contained more albumin (2.25 +/- 0.59 microgram/mg) than other diseases (1.22 +/- 0.55) or normals (1.31 +/- 0.36 microgram/mg) (P less than 0.01-0.001). No differences were observed between the normal and other disease groups. Although there were no differences in hydroxyproline content, there was a highly significant correlation between the concentration of hydroxyproline and albumin in the diabetic TBM (r = 0.82), diabetic GBM (r = 0.70), and normal TBM (r = 0.79). Elution studies with different buffers on frozen sections of diabetic kidneys suggest that the albumin is relatively firmly bound. Although albumin is present in extracellular membranes of normal and diseased human kidneys, the concentration is higher in diabetes mellitus.

Sixty patients of inflammatory brain disease were diagnosed and classified according to clinico-investigational criteria by Ahuja et al into tuberculous meningitis group (36 patients) and non-tuberculous meningitis group (24 patients). Tuberculous meningitis (TBM) patients were classified as probable (9 patients) and possible (27 patients) TBM. Non-TBM group comprised of pyogenic meningitis (8.3%), viral encephalitis (23.3%), cerebral malaria (5%) and enteric encephalopathy (3.3%). Cerebrospinal fluid-adenosine deaminase (CSF-ADA) activities were measured in both TBM and non-TBM groups. Mean CSF-ADA levels in TBM patients was 9.61 +/- 4.10 IU/L and was significantly elevated as compared to viral encephalitis and enteric encephalopathy cases; but difference was insignificant in comparison to pyogenic meningitis (7.92 +/- 0.95 IU/L) and cerebral malaria. Using 8 IU/L as cut off value for diagnosis of TBM a sensitivity of 44% and specificity of 75% was observed.