Continuous positive airway pressure (CPAP) has been used in the treatment of infants with tracheobronchomalacia (TBM). However, the effects of CPAP on lung mechanics in these infants are unknown. We hypothesized that CPAP prevents airway collapse and improves forced exhalation. We studied respiratory mechanics of nine infants (age 15 +/- 3 mo, SEM) with acquired TBM documented by bronchoscopy, during quiet respiration and forced exhalation, using the esophageal balloon and rapid thoracic compression techniques, respectively. Measurements were made when infants received no CPAP and repeated when 5 and 8 cm H2O CPAP were applied to the airway opening via a modified Mapleson anesthesia circuit. Expiratory resistance (RL), midexpiratory tidal flow (VE50), and maximal flow at functional residual capacity (Vmax FRC) were compared at each level of CPAP. Vmax FRC increased threefold from baseline to 8 cm H2O CPAP (p < 0.005). In contrast, there was no difference in expiratory RL or in VE50 at any level of CPAP. These data suggest that in infants with acquired TBM, assessments of forced expiratory flow reflect the amount of CPAP necessary to prevent airway collapse during forced exhalation better than can measurements of tidal mechanics.

The clinical, laboratory and radiological features of 30 children with clinically diagnosed tuberculous meningitis (TBM) who were HIV-seronegative were compared with those of ten HIV-infected children with TBM. Such comparative data are not currently available in the literature and so are an important addition to our knowledge of the HIV-TB co-infection epidemic. In comparison with the HIV-negative children, those infected with HIV were younger, had a shorter duration of symptoms and were more often Mantoux-negative (HIV-positive 23% vs HIV-negative 70%; p = 0.01). On presentation, all children in both groups were in MRC TBM stages II or III. Clinical features were similar in both groups but computed tomography of the brain showed more ventricular enlargement (HIV-positive 80% vs HIV-negative 63%), gyral enhancement (HIV-positive 60% vs HIV-negative 17%; p = 0.01) and cerebral atrophy (HIV-positive 40% vs HIV-negative 17%). Outcome was considerably worse in the HIV-positive children, of whom 30% died (vs HIV-negative 0/30; p = 0.01) and the remainder were moderately (HIV-positive 30% vs HIV-negative 24%) or severely (HIV-positive 30% vs HIV-negative 19%) handicapped at the end of treatment. While clinical features were not markedly different in HIV-infected and uninfected children with TBM, abnormal radiological findings were more common in the HIV-infected group and outcome was considerably worse. Co-existing HIV encephalopathy and diminished immune competence undoubtedly contributed to the more severe clinical and neuro-radiological features.

BACKGROUND

Despite the availability of many investigational methods, diagnosis of Tuberculous meningitis (TBM) is extremely difficult. Polymerase chain reaction (PCR), using specific primers for Mycobacterium tuberculosis (MTB), shows variable sensitivity and specificity. In this study, we assessed the usefulness of the PCR assay for TBM diagnosis and compared it to our in-house enzyme-linked immunosorbent assay (ELISA) based on antigen 85 complex detection.

METHODS

Cerebrospinal fluid (CSF) samples were obtained from 189 patients in 3 different groups: confirmed TBM (n=13), clinically suspected TBM (n=37), and non-TBM (n=139). A PCR assay was performed using a specific pair of primers designed to amplify the insertion sequence IS6110 in the MTB genome, and it was compared to ELISA, using monoclonal antibodies against the purified Ag 85 complex, to analyze CSF samples and diagnose TBM.

RESULTS

The PCR assay yielded sensitivity and specificity values of 80% and 84%, which are slightly less, but comfortable to the values obtained for the ELISA method (84% and 91%). Interestingly, a combinatorial approach using both methods provided sensitivity and specificity of 88% and 93%.

CONCLUSIONS

The PCR assay was found to be as sensitive and specific as the well-established in-house ELISA technique, suggesting that it can be used for TBM diagnosis.

An enzyme-linked immunosorbent assay (ELISA) was studied as a possible laboratory test to aid in the diagnosis of tuberculous meningitis (TBM) in an Indian population. The assay detected mycobacterial antibodies in the cerebrospinal fluid (CSF) of TBM patients. Three antigens, PPD, BCG and M. tuberculosis were tested for use in the assay and of these, M. tuberculosis was found to be the most suited. A sensitivity of 72% and specificity of 92% with M. tuberculosis as antigen was obtained for the ELISA under discussion. The system therefore does hold promise as a diagnostic laboratory test for TBM.

BACKGROUND

With the introduction of the α1, 3-galactosyltransferase gene-knockout (GT-KO) pig and its pivotal role in preventing hyperacute rejection (HAR), coagulation remains a considerable obstacle yet to be overcome in order to provide long-term xenograft survival. Thrombomodulin (TBM) plays a critical anticoagulant and anti-inflammatory role in its part of the protein C pathway. Many studies have demonstrated the strong anticoagulant effects of TBM in xenotransplantation, but its complement regulatory effects have not been appropriately examined. Here, we investigate whether TBM can regulate complement activation as well as coagulation in response to xenogeneic stimuli.

METHODS

We transfected porcine endothelial cells (MPN-3) with adenovirus vectors containing the human TBM gene (ad-hTBM), or a control gene containing GFP (ad-GFP). The expression level of ad-hTBM was measured by flow cytometry. To confirm the anticoagulant effect of TBM, coagulation time was measured after treatment with recalcified human plasma in ad-hTBM-transfected MPN-3, and a thrombin activity assay was performed after treatment with 50% human serum in ad-hTBM-infected MPN-3.

RESULTS

Thrombin generation was significantly decreased in a dose-dependent manner in ad-TBM group, and coagulation time was increased in the ad-hTBM group when compared to the ad-GFP group. Complement-dependent serum toxicity assays were performed after treatment with 20% human serum or heat-inactivated human serum by LDH assay. Complement-dependent toxicity was significantly attenuated in the ad-hTBM group, but complement-independent toxicity was not attenuated in the ad-hTBM group. These results suggest that human thrombomodulin (hTBM) has complement regulatory effects as well as anticoagulant effects. To further investigate the mechanisms of complement regulation by hTBM, we deleted the EGF5, 6 domains that are involved in thrombin generation or the lectin-like domain involved in inflammation of TBM and functional tests were performed using these modified forms. We showed that the EGF5, 6 domain of TBM principally inhibits complement activation rather than the lectin domain.

CONCLUSIONS

The EGF5, 6 domains of TBM appear to be the major domains for down-regulating the complement system rather than the lectin-like domain during xenogenic stimuli. The role of EGF5, 6 domains of hTBM may be due to inhibition of thrombin as thrombin can cleave C3a and C5a directly and hTBM may also be involved in complement regulation. Clearly then human TBM has complement regulatory effects as well as anticoagulant effects in xeno-immune response, and it is a promising target for attenuating xenograft rejection.

Tuberculosis (TB) which is caused by Mycobacterium tuberculosis infects primarily the lungs but it also affects other parts of the body. Tuberculous meningitis (TBM) is the most severe form of TB and has the highest mortality and morbidity rate compared to other forms of TB. It is common in young children and HIV-infected patients, but is also seen in adults. Despite anti-tuberculosis treatment, TBM is still a major cause of death and neurological sequelae as treatment given to the patients is often delayed. Early diagnosis is challenging due to the non-specific symptoms of TBM and the low number of tubercle bacilli in cerebrospinal fluid (CSF). Until now, there is no established diagnostic method that can rapidly detect M. tuberculosis in TBM patients with high sensitivity and specificity. The emergence of drug resistant M. tuberculosis strains further complicates the diagnosis and treatment regimen of TBM. This review summarizes challenges of the currently used diagnostic methods and the potential future use of molecular diagnostic methods for TBM.

Morphological study of the kidney is generally the first step in the diagnosis of Alport's syndrome. Light microscopy study allows to suggest the diagnosis with the association of focal and segmental glomerulosclerosis, GBM anomalies when studied with silver staining, interstitial foam cells, and negative standard immunofluorescence study. GBM anomalies observed by electron microscopy are nearly specific with thickening splitting and fragmenting of the lamina densa. GBM anomalies are the consequence of a collagen IV disease. Thus, immunohistochemical results obtained with 6 different alpha(IV) are essential and allow to evaluate the mode of inheritance. Schematically, in the X dominant AS form, GBM, distal tubular BM and collecting duct BM do not express alpha3/alpha4, alpha5(IV). In the autosomic recessive AS form, collecting duct BM alone express alpha5(IV) without expression of alpha3(IV) and alpha5(IV) chains along the GBM and distal TBM.

In order to analyze the role of phagocytic cells in experimental antitubular basement membrane (TBM) antibody-mediated nephritis, Hartley guinea pigs (GP) were immunized with rabbit tubular basement membrane (TBM) in complete Freund's adjuvant and pertussis vaccine. Renal tissue was obtained 10 to 15, 15 to 25, and 25 to 35 days after the start of immunization. Severe renal tubulointerstitial (RTI) nephritis developed in 95% of the animals. Linear deposits of IgG and C3 along TBM were seen 10 days after initial immunization. A few days later, monocytes and macrophages infiltrated the interstitium and subsequently differentiated into epithelioid and foreign body-type giant cells (GC). The GC were most actively involved in the destruction of the TBM: Cytoplasmic pseudopodia of the GC adhered to the TBM; the areas of membrane apposition were several microns in length; no evidence of specialization was found in the plasma membrane adjoining the TBM; no cellular organelles, except for abundant microfilaments, were seen in the contact regions. The initial contact was followed by lysis of plasma membrane of the GC and TBM, perforation of TBM, and phagocytosis of TBM fragments. Concomitantly, fluorescent staining for IgG along the TBM became discontinuous or disappeared. Destruction of TBM was accompanied by degeneration of tubular epithelial cells and collapse of tubular architecture. The morphologic observations are consistent with the hypothesis that, in GP, autoimmune RTI nephritis damage of TBM results from the cooperation of humoral and cellular mechanisms, probably akin to those of antibody-mediated lymphocytotoxicity.

Pre- and post-transplant predictive factors of graft survival for optimal and expanded criteria grafts have been studied in the past. The goal of our study was to evaluate the recent large set of United Network of Organ Sharing records (1990-1998) to generate a prediction algorithm of 3-yr graft survival based on pre-transplant variables alone. The dataset of patients with end-stage renal disease and cadaveric kidney or kidney-pancreas transplantation (1990-1998) used in the study consisted of 37,407 records. Logistic regression (LM) and a tree-based model (TBM) were used to identify predictors of 3-yr allograft survival and to generate prediction algorithm. Donor and recipient demographic characteristics (age, race, and gender) and body mass index showed non-linear, while human leukocyte antigen match showed strong linear relationships with 3-yr graft survival. Prediction of the probability of graft survival from the model, achieved a good match with the observed survival of the separate dataset, with a correlation of r = 0.998 for LM and r = 0.984 for TBM. The positive predictive value (PV) of allograft survival with LM and TBM was 76.0% and the negative PV was 63 and 53.8% for LM and TBM, respectively. Both LM and the TBM can potentially be used in clinical practice for long-term prediction of kidney allograft survival based on pre-transplant variables.

OBJECTIVE

Autopsy evaluation of tracheobronchomalacia (TBM) in patients with Duchenne muscular dystrophy (DMD) who were receiving long-term ventilation through uncuffed tracheostomies.

METHODS

Necropsies were performed in seven patients with DMD who had received positive-pressure ventilation through uncuffed tracheostomies for a duration of 5 to 30 years.

METHODS

Rehabilitation facility affiliated with a university medical center.

RESULTS

The range of peak airway pressures sustained during ventilation by all the patients was 23 mm Hg to 36 mm Hg. Bronchoscopy (which was performed in four of the five patients) detected tracheomalacia in only one of the patients. Five of the seven patients demonstrated variable degrees of airway malacia. Two patients also had tracheal perforations, one of which resulted in a fatal hemorrhage from a tracheovascular fistula.

CONCLUSIONS

Given enough time, patients receiving positive-pressure ventilation can develop airway thinning and dilation even without the use of an inflated tracheostomy cuff. There is also a potential for tracheal erosion into an adjacent artery that can lead to fatal hemorrhage. Such findings also have implications for individuals receiving noninvasive positive-pressure ventilation, who could develop TBM as a result of the continuous cycling pressures on the airway wall.

BACKGROUND

Focal basal meningeal enhancement may produce a confusing CT picture in children with suspected tuberculous meningitis (TBM).

OBJECTIVE

To demonstrate the incidence, distribution and appearance of localized basal meningeal enhancement in children with TBM.

METHODS

CT scans of patients with definite (culture proven) and probable (CSF suggestive) TBM were retrospectively evaluated by two observers. Localized basal enhancement was documented as involving: unilateral cistern of the lateral fossa (CLF), unilateral sylvian fissure, unilateral CLF and sylvian fissure in combination, unilateral CLF and sylvian fissure with ipsi- or contralateral ambient cistern and isolated quadrigeminal plate cistern.

RESULTS

The study included 130 patients with TBM (aged 2 months to 13 years 9 months). Focal basal enhancement was seen in 11 patients (8.5%). The sylvian fissure was involved most commonly, followed by the lateral fossa cistern. The ambient cistern was involved in three patients and the quadrigeminal plate cistern in one. Focal areas of enhancement corresponded to the areas of infarction in every patient.

CONCLUSIONS

Focal basal meningeal enhancement is common (8.5%) in paediatric TBM. This must be kept in mind when evaluating CT scans in children presenting with focal neurological findings, seizures or meningism in communities where TBM is endemic.

Schistosomiasis prevalence and egg counts remained low one year after chemotherapy in most households in a hyperendemic rural area in northern Minas Gerais but several distinct spatial patterns could be observed in relation to IgE levels and to a lesser extent to exposure risk (TBM) and type of water supply. An inverse relationship between pre-treatment household prevalence and egg counts on the one hand and post-treatment IgE levels on the other were noted in two of the five communities. Low exposure risk was associated with the low pre-treatment infection rates in the central village but did not contribute to the decline of infection rates after chemotherapy in the study area, as indicated by the significant increase in water contact during the posttreatment period (p < 0.0001). Distance between households and the streams and socioeconomic factors were also unimportant in predicting the spatial distribution of infection. These results are consistent with the production and antiparasitic effect of high levels of IgE in Schistosoma mansoni infection.

Physiological events at the time of fertilization of pig oocytes may differ in vitro depending on the in vitro fertilization (IVF) medium. This hypothesis was tested by in vitro maturation of pig oocytes for 44 h in NCSU-37 medium and thereafter fertilization with frozen-thawed ejaculated spermatozoa. Three different IVF media (TCM-199, Tyrode's albumin lactate pyruvate (TALP) and Tris-buffered medium (TBM)) were used. For the acrosome reaction test, spermatozoa were incubated for 0-150 min in the three IVF media, and the proportion of live acrosome-reacted and acrosome-intact cells was determined by fluorescein isothiocyanate-labelled peanut agglutinin (FITC-PNA) and propidium iodide (PI) staining. The cortical granule density of oocytes was evaluated by confocal microscopy, 2.5 and 5.0 h after culture in each medium in the presence or absence of spermatozoa. Zona pellucida resistance to pronase digestion was also determined in the same groups. The percentages of penetration, monospermy, male pronucleus formation, cleavage and blastocyst formation, and the number of cells per blastocyst after culture were determined. The results indicate that the acrosome reaction occurred much faster in TBM than in TCM-199 or TALP medium. Continuous cortical granule synthesis was observed in the three media when oocytes were incubated in the absence of spermatozoa. The presence of spermatozoa triggered the cortical reaction in a large proportion of oocytes fertilized in TCM-199 and TALP media. On the basis of the duration of pronase digestion, the zona pellucida of oocytes incubated in TCM-199 was harder (407.7 +/- 35.5 s) than that of oocytes cultured in TALP (235.4 +/- 18.2 s) or TBM (189.1 +/- 16.8 s). No zona pellucida hardening was noted in oocytes after insemination in any of the media. The percentages of penetration and cleavage were higher in oocytes cultured in TCM-199 and TALP than in TBM. The percentage of monospermy was higher in TCM-199 and TBM than in TALP. No effect of the medium was shown on the percentage of blastocyst formation or on the number of cells per blastocyst. In conclusion, the results highlight how differently the fertilization events take place in each IVF medium and how far these IVF media still are from achieving biological properties of gametes close to those observed in the physiological setting.

OBJECTIVE

To evaluate the predictors of neurological sequel in tuberculous meningitis (TBM).

METHODS

This study was carried out at the Department of Clinical Microbiology and Infectious Diseases, Haseki Training and Research Hospital, Istanbul, Turkey, between January 1998 and March 2009. Neurological sequels at 6 months of 160 adult patients with TBM who had been followed up were assessed retrospectively. The prognostic role of various demographic, clinical, laboratory, and radiological findings on admission, in prediction of neurological sequel development, were studied using a multivariate logistic regression. Clinical and therapeutic outcomes at 6 months were determined using a modified Barthel Index.

RESULTS

Twenty-seven (17%) patients died and 20 (13%) survivors had neurological sequelae at 6 months. Cranial nerve palsy, presence of tuberculoma, younger age, and basal meningitis were found to be significant predictors of neurological sequelae in univariate analysis, but only younger age (odds ratio [OR] 2.9, 95% confidence intervals [CI] 1.0-8.6, p=0.049), cranial nerve palsy (OR 3.9, 95% CI 1.8-8.8, p=0.001), and presence of tuberculoma (OR 1.9, 95% CI 1.0-4.2, p=0.048) were found to be significant predictors using multivariable logistic regression analysis.

CONCLUSIONS

Neurological sequelae were more common in patients with tuberculoma and cranial nerve palsy on admission. Development of neurological complications may be seen despite timely and effective anti-tuberculous therapy especially in younger patients.

OBJECTIVE

To determine how many more patients would be treated when lowering the treatment threshold for tuberculous meningitis.

METHODS

From 1989 to 2004 findings of patients with symptoms lasting more than 1 week and inflammatory changes of cerebrospinal fluid (CSF) were collected. Several models of latent class analysis were tested. Cumulative numbers of cases were plotted against different cut-offs for post-test probability.

RESULTS

In a cohort of 232 patients the prevalence of tuberculous meningitis (TBM) was estimated at 79.8% (95% CI. 67,0-88,1); probabilities above 80% were reached in 73% of patients. Lowering this threshold from 80% to 20% would add 14% more patients to be treated, for a total of 87%. A further lowering of the threshold to 5% would imply 5% more patients to be treated, bringing the cumulative number to 92%. The difference of lowering the threshold from 80% to 5% was 19%.

CONCLUSIONS

In this setting, at least 75% of patients showing suggestive symptoms for more than a week and CSF changes very probably had TBM. The number of patients that should be treated does not increase linearly when lowering the threshold.

BACKGROUND

Abnormalities on CT imaging may contribute to the diagnosis of tuberculous meningitis (TBM). Recently, an expert consensus case definition (CCD) and set of imaging criteria for diagnosing basal meningeal enhancement (BME) have been proposed. This study aimed to evaluate the sensitivity, specificity and reliability of these in a prospective cohort of adult meningitis patients.

METHODS

Initial diagnoses were based on the CCD, classifying patients into: 'Definite TBM' (microbiological confirmation), 'Probable TBM' (diagnostic score ≥10), 'Possible TBM' (diagnostic score 6-9), 'Not TBM' (confirmation of an alternative diagnosis) or 'Uncertain' (diagnostic score of <6). CT images were evaluated independently on two occasions by four experienced reviewers. Intra-rater and inter-rater agreement were calculated using the kappa statistic. Sensitivities and specificities were calculated using both 'Definite TBM' and either 'Definite TBM' or 'Probable TBM' as gold standards.

RESULTS

CT scan criteria for BME had good intra-rater agreement (κ range 0.35-0.78) and fair to moderate inter-rater agreement (κ range 0.20-0.52). Intra- and inter-rater agreement on the CCD components were good to fair (κ = ranges 0.47-0.81 and 0.21-0.63). Using 'Definite TBM' as a gold standard, the criteria for BME were very specific (61.5%-100%), but insensitive (5.9%-29.4%). Similarly, the imaging components of the CCD were highly specific (69.2-100%) but lacked sensitivity (0-56.7%). Similar values were found when using 'Definite TBM' or 'Probable TBM' as a gold standard.

CONCLUSIONS

The fair to moderate inter-rater agreement and poor sensitivities of the criteria for BME suggest that little reliance should be placed in these features in isolation. While the presence of the CCD criteria of acute infarction or tuberculoma(s) appears useful as rule-in criteria, their absence is of little help in excluding TBM. The CCD and criteria for BME, as well as any new criteria, need to be standardized and validated in prospective cohort studies.

The clinical features and quantitative renal morphometry, including the index of mesangial expansion (IME), the index of arteriolar hyalinous change (IAHC), the percentage of globally sclerosed glomeruli (%GS), and interstitial volume fraction for total renal cortex (Vv int/T) of 67 Japanese non-insulin dependent diabetes mellitus (NIDDM) patients were examined. For the total subject population, Vv int/T correlated with urine protein, creatinine clearance, blood pressure, IME, IAHC and %GS, but not with duration of NIDDM. No significant difference in interstitial expansion between normo- and microalbuminuric patients was observed, and Vv int/T did not correlate with urine albumin excretion rate in those patients. However, in the area without hyalinized glomeruli and atrophic tubules, we found significant interstitial expansion and thickening of the tubular basement membrane (TBM) in patients without overt proteinuria as compared with those in the age-matched minimal change control group. This study confirmed that interstitial expansion in NIDDM progresses in parallel with glomerular and arteriolar lesions and that the expansion occurs concurrently with TBM thickening before the appearance of proteinuria.

The measurement of adenosine deaminase (ADA) level in cerebrospinal fluid (CSF) has generated as a suitable test for tuberculous meningitis (TBM) diagnosis. The main objective in the present meta-analysis focused on analyzing the ADA test accuracy in order to diagnose TBM.

We searched several databases including Medline, Embase and Cochrane databases to identify studies addressing the diagnosis of TBM. The quality of included reports were assessed by RevMan5 software (via QUADS2 checklist). Accuracy measures of ADA test (sensitivity, specificity and others) pooled with random effects models. In addition, the data was elicited by using midas and metan packages in stata (version 12).

Twenty studies were eligible for inclusion within the meta-analysis. The pooled sensitivity and specificity for TBM diagnosis hallmarks were 89% (95% CI: 0.84-0.92) and 91% (95% CI: 0.87-0.93), respectively. The positive likelihood ratio was 9.4 (95% CI: 7-12.8), negative likelihood ratio was 0.12 (95% CI: 0.09-0.17), and diagnostic odds ratio was 77 (95% CI: 45-132). Indeed, the area under the summary receiver operating characteristic (SROC) was 0.96.

It was magnificently attained that ADA test had a relatively high accuracy for TBM diagnosis.

Renal biopsies and autopsy specimens of 23 patients with light chain deposition disease (LCDD) and one with only heavy chain deposits, were studied by light (LM) and electron microscopy (EM) as well as immunohistology (IH). Thirteen patients had multiple myeloma; 1 had lymphoma, and 1 chronic myeloid leukaemia with polycythaemia vera. In nine patients, no lymphoproliferative disease was identified. The LM lesions most suggestive of LCDD, nodular glomerulosclerosis (NS) and thickening and wrinkling of the tubular basement membranes (TBM), were present in only ten and 13 patients, respectively. In five of seven specimens without NS or TBM thickening by LM, EM was negative, indicating a limited value of EM in confirming the diagnosis. Renal amyloidosis was not identified, but in one patient amyloid in the heart and tongue was seen at autopsy. One patient had both granular and extensive glomerular non-amyloid fibrillary deposits. In two patients myeloma casts were identified. Twenty-one patients showed renal LC immune reactivity, 1 had both alpha heavy and lambda LC, 1 had only detectable gamma heavy chain. One biopsy was negative by IH, but had characteristic electron dense deposits. In six patients with immune reactivity to LC, no electron dense deposits could be identified by EM. This study emphasizes the spectrum of renal changes by LM and EM in LCDD, the frequent lack of consistency between deposits detected by IH and EM and the difficulty in coming to a definite diagnosis without LM, EM and IH. The results of this study and examination of the literature indicates that extensive morphological changes are more often present in kappa than in lambda LCDD.

BACKGROUND

Diagnosing tuberculous meningitis (TBM) remains problematic despite many new advanced diagnostic methods. Adenosine deaminase (ADA) assays have emerged as novel alternatives to other costly and time-consuming methods for TBM diagnosis. In the present study the usefulness of the ADA method was assessed for the diagnosis of TBM and compared with an in-house developed ELISA method for detecting the antigen 85 (Ag 85) complex of M. tuberculosis in cerebrospinal fluid (CSF) samples of suspected and culture-confirmed TBM patients.

METHODS

ADA activity in CSF was determined at 37 degrees C according to the method of Guisti and Galanti. ELISA, employing monoclonal antibodies against the purified Ag 85 complex, was used to demonstrate Ag 85 complex in CSF from TBM patients. CSF samples were obtained from 153 patients in three different groups: confirmed TBM (n=27), clinically suspected TBM (n=39), and non-TBM (n=87).

RESULTS

The ADA method yielded sensitivity and specificity of 83% and 86%, which are similar to those of the ELISA method (89% and 90%). The correlation between the Ag 85 complex activity in absorbance by ELISA and the ADA activity obtained in units per liter per minute (U/l/min) was also positive and significant. (Pearson's correlation coefficient r=0.3234, 95%CI: 0.1621-0.4679, p<0.001).

CONCLUSIONS

This study suggests that the ADA method can be performed for TBM diagnosis in low-income TB-affected regions where more sophisticated facilities are generally not available.

The possible development of hepatotoxic effects as a result of high dosages of isoniazid, rifampin, pyrazinamide, and ethionamide was assessed in 56 young children (median age, 22 months) treated for severe tuberculous meningitis (TBM). Only one of the 56 children became jaundiced, probably as result of hepatitis A infection. Of 33 children observed for at least eight weeks, only five (15%) had normal serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase levels throughout, but in only three patients were AST or ALT values greater than 200 U/L, and enzyme levels tended to normalize toward the end of the period. In this group of 33 children, those at stage III TBM had higher enzyme levels than did those at stage II. The remaining 23 children were observed for a mean period of only four weeks, and 18 (75%) had at least one abnormal liver function test result.

Blood-brain barrier (BBB) function and cerebrospinal fluid (CSF) biomarkers were measured in patients admitted to hospital with severe neurological infections in the Lao People's Democratic Republic (N = 66), including bacterial meningitis (BM; N = 9) or tuberculosis meningitis (TBM; N = 11), Japanese encephalitis virus (JEV; N = 25), and rickettsial infections (N = 21) including murine and scrub typhus patients. The albumin index (AI) and glial fibrillary acidic protein (GFAP) levels were significantly higher in BM and TBM than other diseases but were also raised in individual rickettsial patients. Total tau protein was significantly raised in the CSF of JEV patients. No differences were found between clinical or neurological symptoms, AI, or biomarker levels that allowed distinction between severe neurological involvement by Orientia tsutsugamushi compared with Rickettsia species.

BACKGROUND

Cytokines are intercellular polypeptide messengers that mediate immune and inflammatory responses. The temporal profile of interleukin-1 beta (IL-1 beta), IL-6, tumor necrosis factor alpha (TNF-alpha), and monocyte chemotactic protein 1 (MCP-1) expression was examined in anti-tubular basement membrane (TBM) antibody-associated tubulointerstitial nephritis (TIN).

METHODS

TIN was induced by immunization of Brown Norway rats with bovine cortical TBM, whereas control rats received ovalbumin. Whole kidney RNA was assessed with the RNase protection assay 3, 7, 8, 9, 10, 12, and 14 days after immunization. Cytokine mRNA expression was correlated with TNF-alpha bioactivity, renal intercellular adhesion molecule-1 expression, and CD18-positive leukocyte infiltration by immunohistochemistry.

RESULTS

Increased IL-1 beta, TNF-alpha, and MCP-1 mRNA relative to glyceraldehyde-3-phosphate dehydrogenase appeared on day 7 when TIN involved 10 to 40% of the cortex, and peaked rapidly on day 8 when there was 60 to 80% cortical involvement (at which time 75 to 80% of the infiltrating cells were neutrophils). The increase in TNF-alpha mRNA correlated with increased bioactivity. The influx of mononuclear cells on day 8 was preceded by the expression of MCP-1 mRNA. The infiltrating leukocytes expressed the leukocyte beta 2-integrin (CD18) and were found in areas with increased intercellular adhesion molecule-1 expression. The mRNAs for IL-1 beta, TNF-alpha, and MCP-1 were undetectable by day 10 (at which time 95% of the infiltrating cells were mononuclear). An increase in IL-1 receptor antagonist mRNA paralleled those of IL-1 beta. The expression of IL-6 mRNA was similar to that for IL-1, except that it disappeared by day 9.

CONCLUSIONS

There is a temporal association in the expression of IL-1 beta, TNF alpha, MCP-1, and IL-6 with the upregulation of intercellular adhesion molecule-1 and leukocyte infiltration within the tubulointerstitium in anti-TBM antibody-associated TIN. The narrow window of time through which these cytokines are expressed and the coincidence of their peak expression on day 8 suggest complex cytokine interactions in the pathogenesis of anti-TBM antibody TIN.

BACKGROUND

Controlled studies investigating risk factors for the common presenting problem of chronic cough in dogs are lacking.

OBJECTIVE

To identify demographic and historical factors associated with chronic cough in dogs, and associations between the characteristics of cough and diagnosis.

METHODS

Dogs were patients of an academic internal medicine referral service. Coughing dogs had a duration of cough>or=2 months (n=115). Control dogs had presenting problems other than cough (n=104).

METHODS

Owners completed written questionnaires. Demographic information and diagnoses were obtained from medical records. Demographic and historical data were compared between coughing and control dogs. Demographic data and exposure to environmental tobacco smoke (ETS) also were compared with hospital accessions and adult smoking rates, respectively. Characteristics of cough were compared among diagnoses.

RESULTS

Most coughing dogs had a diagnosis of large airway disease (n=88; 77%). Tracheobronchomalacia (TBM) was diagnosed in 59 dogs (51%), including 79% of toy breed dogs. Demographic risk factors included older age, smaller body weight, and being toy breed (P<.001). No association was found between coughing and month (P=.239) or season (P=.414) of presentation. Exposure to ETS was not confirmed to be a risk factor (P=.243). No historical description of cough was unique to a particular diagnosis.

CONCLUSIONS

Associations with age, size, and toy breeds were strong. TBM is frequent in dogs with chronic cough, but descriptions of cough should be used cautiously in prioritizing differential diagnoses. The association between exposure to ETS and chronic cough deserves additional study.