Cerebrospinal fluid matrix metalloproteinase 9 levels, blood-brain barrier permeability, and treatment outcome in tuberculous meningitis.

OBJECTIVES: Tuberculous meningitis is characterized by elevated levels of matrix metalloproteinase 9 (MMP9) in the cerebrospinal fluid (CSF). However, it is unclear whether elevated MMP9 levels are associated with poor treatment outcome. We tested the hypothesis that pretreatment MMP9 levels in the CSF would be higher in tuberculous meningitis patients experiencing a poor treatment outcome. METHODS: We prospectively assessed the treatment outcome in a consecutive sample of human immunodeficiency virus-negative patients with tuberculous meningitis. We defined good outcome as survival without severe neurological disability (modified Rankin scale scores 0-2). We estimated levels of MMP9 and its tissue inhibitor (TIMP1) on pretreatment CSF samples. We used albumin index to assess blood-brain barrier permeability. RESULTS: We studied 40 patients (23 males [58%]) with tuberculous meningitis. Sixteen patients (40%) had stage 3 disease. On follow-up, 18 (45%) patients had a poor treatment outcome-15 patients died and 3 had severe neurological disability. Pretreatment MMP9 levels were not associated with treatment outcome (median [interquartile range], 254 [115-389] vs. 192 [60-383] ng/mL in good vs. poor outcome groups; P = 0.693). MMP9 levels did not correlate with the albumin index (Spearman's rho = 0.142; P = 0.381). However, MMP9 levels significantly correlated with CSF glucose levels (rho = -0.419; P = 0.007) and admission Glasgow coma scale score (rho = 0.324; P = 0.032). Likewise, TIMP1 levels also did not differ by treatment outcome (1239 [889-1511] vs. 1522 [934-1949] ng/mL; P = 0.201). MMP9/TIMP1 ratio that reflects net proteolytic activity was also not different between the two groups (0.191 [0.107-0.250] vs. 0.163 [0.067-0.34]; P = 0.625). CONCLUSION: Our findings do not support the hypothesis that pretreatment levels of MMP9 would be higher in tuberculous meningitis patients experiencing a poor treatment outcome. Further, MMP9 levels in the CSF did not correlate with blood-brain barrier permeability in patients with tuberculous meningitis.

Awareness of blood-borne infections and burden of occupational exposures to blood and body fluids among health care personnel in a tertiary care teaching hospital.

BACKGROUND AND OBJECTIVES: Occupational exposures (OEs) to blood and body fluids (BBFs) pose significant risk of transmission of blood-borne infections (BBIs) to health care personnel (HCP) and are grossly underreported. We aimed to study the awareness of BBIs and their prevention, burden of OEs, assess factors contributing to them and their poor reporting and assess the practices for their prevention among HCP. MATERIALS AND METHODS: This cross-sectional study conducted at a tertiary care teaching hospital located in south India used a self-administered questionnaire to assess the awareness of BBIs, attitude and practice of HCP for prevention of OEs, and to quantify the burden of exposures. All formally self-reported OEs during the study period of 2 years were documented prospectively. RESULTS: Majority (369/401, 92%) of HCP surveyed had fair general awareness of BBIs. Though 90% were aware of the concept of universal precautions (UPs), self-reported adherence to barrier precautions was acceptable in only 80%. Overall, 56% and 46% of HCP were aware of human immunodeficiency virus (HIV) and hepatitis B post-exposure prophylaxis (PEP) respectively. Eighteen percent (74/401) were either not vaccinated or incompletely vaccinated against hepatitis B. Recapping of used needles was reported by 79% (317/401). Nearly half (208/401) reported OEs over preceding year and 70% (146/208) of exposed had not formally reported them. Over the 2-year study period, 53 formally self-reported exposures were documented prospectively. Needle stick injuries accounted for 83% of the exposures, and appropriate personal protective devices were not being used during 47% of exposures. Though doctors had the highest awareness, they reported lowest adherence to barrier precautions and highest burden of exposures (P < 0.05). CONCLUSION: Though majority of HCP had fair awareness of BBIs, it did not translate into adequate adherence to UPs and safe practices. High burden of OEs and their poor reporting emphasize the need to motivate our HCP to adhere to safe work practices and to promptly seek professional counselling after exposures. There is an urgent need to educate HCP about the availability and effectiveness of PEP for HIV and hepatitis B. A uniform national policy for prevention and reporting of OEs has to be framed.

Angiogenesis and proliferation index in patients with acute leukemia: a prospective study.

Angiogenesis and proliferation as measured by microvessel density (MVD) and proliferation index (PI) are essential correlates of malignancy. The aim of our study was to evaluate difference between these values in AML and ALL and also to study the modulation in these parameters following achievement of remission in acute lymphoblastic leukemia. Differences between adult and adolescent cases of acute leukemia in relation to these values were also studied. We also tried to assess the relationship between angiogenesis and proliferation. Fifty-five patients with acute leukemia were included in the study. Trephine biopsies were immunostained with CD34 and factor VIIIrAg to demonstrate angiogenesis measured as MVD. Immunostaining with PCNA and Ki-67 was done to study proliferation. We found a significant increase in MVD and PI in cases when compared with controls (P < 0.0001). In addition cases with ALL had a significantly higher MVD compared to those with AML (P < 0.01). The patients with ALL who went into remission showed a significant reduction in MVD; PI remained high. The cases which did not achieve remission showed no significant reduction in either MVD or PI. All adolescent cases of ALL were similar to adults with respect to MVD and PI.

Effects of gender on sympathovagal imbalance, prehypertension status, and cardiovascular risks in first-degree relatives of type 2 diabetics.

BACKGROUND: Although cardiovascular (CV) risks are reported in first-degree relatives (FDRs) of type 2 diabetics, effects of gender on sympathovagal imbalance (SVI) and CV risks in these subjects have not been investigated. METHODS: Body mass index (BMI), blood pressure variability parameters including baroreflex sensitivity (BRS), spectral indices of heart rate variability, autonomic function tests, insulin resistance, lipid profile, inflammatory markers (interleukin 6, high-sensitivity C-reactive protein, tumor necrosis factor α) and oxidative stress (OS) marker were measured and analyzed in control group (without family history of diabetes; 65 women, 60 men) and study group (FDRs of type 2 diabetics; 52 women, 49 men) subjects. RESULTS: BMI, heart rate, blood pressure, rate-pressure product, stroke volume, left-ventricular ejection time, cardiac output, total peripheral resistance, homeostatic model of insulin resistance, lipid profile, inflammatory and OS markers, and ratio of low-frequency to high-frequency power of heart rate variability (LF-HF ratio), a sensitive marker of SVI, were significantly increased, and BRS was significantly decreased in study group men compared with women. SVI was more intense in men and was due to concomitant sympathetic activation and vagal inhibition. There was no SVI in control subjects. Multiple regression analysis demonstrated independent contribution of BMI, homeostatic model of insulin resistance, atherogenic index, inflammatory and OS markers, and BRS to LF-HF ratio. Logistic regression analysis demonstrated significant prediction of prehypertension status and rate-pressure product (markers of CV risk) by LF-HF, which was more prominent in men. CONCLUSIONS: SVI is more intense in male FDRs of type 2 diabetics, and SVI is associated with increased CV risk due to insulin resistance, dyslipidemia, inflammation, and oxidative stress in these subjects.

Association of sympathovagal imbalance with cardiovascular risks in young prehypertensives.

Although cardiovascular (CV) risks have been reported in prehypertension, their link to sympathovagal imbalance (SVI) has not been investigated. In the present study, we have assessed the factors contributing to SVI and the prediction of CV risk by SVI in prehypertensives. Body mass index, CV parameters such as heart rate, systolic blood pressure (BP), diastolic BP, mean arterial pressure, rate-pressure product (RPP), stroke volume, left ventricular ejection time, cardiac output, total peripheral resistance, baroreflex sensitivity recorded by continuous blood pressure variability monitoring using Finapres, autonomic function tests recorded by spectral analysis of heart rate variability (HRV), and heart rate and BP responses to standing, deep breathing, and isometric handgrip, and biochemical parameters such as homeostatic model assessment of insulin resistance, lipid risk factors, inflammatory markers, thyroid profile, and renin and oxidative stress parameters were analyzed in young normotensives (n = 118) and prehypertensives (n = 58). Contribution of CV risks to low-frequency/high-frequency (LF/HF) ratio of HRV, the marker of SVI, was determined by multiple regression analysis, and prediction of SVI to RPP, a known CV risk, was assessed by logisitic regression adjusted for body mass index. BP variability, HRV, and autonomic function test parameters were significantly altered in prehypertensives and these parameters were correlated with LF/HF. Insulin resistance, dyslipidemia, inflammation, and oxidative stress contributed to SVI in prehypertensives. LF/HF and baroreflex sensitivity had significant prediction of RPP in prehypertensives. In conclusion, SVI in young prehypertensives is due to both increased sympathetic and decreased vagal tone. CV risks are linked to SVI and SVI predicts cardiac risk in prehypertensives.

Reliability of Kirby-Bauer disk diffusion method for detecting meropenem resistance among non-fermenting gram-negative bacilli.

BACKGROUND: Meropenem is empirically used as a last resort for the treatment of infections by non-fermenting gram-negative bacilli (NFGNB). Minimum inhibitory concentration (MIC) determined using agar or broth dilution methods is widely used for testing meropenem resistance. However, it is not possible in resource-poor settings. AIM: A prospective study was performed to evaluate the reliability of Kirby-Bauer disk diffusion (KBDD) method for detecting meropenem resistance among NFGNB. MATERIALS AND METHODS: A total of 146 NFGNB consisting of 56 Acinetobacter baumannii, 24 Acinetobacter lwoffii, 48 Pseudomonas aeruginosa and 18 Pseudomonas spp. were included in the study. All the isolates were tested simultaneously by both KBDD method and agar dilution method. RESULTS: Very major errors were not observed with A. baumannii, A. lwoffii and P. aeruginosa, while other Pseudomonas spp. showed a very major error rate of about 5.6%. The major error rates observed with A. baumannii, A. lwoffii, P. aeruginosa and Pseudomonas spp. were 1.8%, 0%, 2.1% and 28.6%, respectively. All the isolates showed a good correlation between zone diameters (KBDD method) and MICs (agar dilution method). The sensitivity and specificity of KBDD method for detecting meropenem resistance was above 90% for all the NFGNB except Pseudomonas spp. CONCLUSIONS: The KBDD method can be reliably used for routine testing of meropenem resistance in A. baumannii, A. lwoffii and P. aeruginosa. However, further studies are needed before employing this technique for detecting meropenem resistance in Pseudomonas spp.

Effect of antihypertensive drug therapy on short-term heart rate variability in newly diagnosed essential hypertension.

1. Abnormalities of cardiac autonomic regulation are a potential mechanism for morbidity despite blood pressure (BP) lowering in hypertension. Analysis of short-term (5 min) heart rate variability (HRV) provides a non-invasive probe of autonomic regulation of sino-atrial (SA) node automaticity. 2. We hypothesized that antihypertensive drug therapy would be associated with an increase in 5 min overall HRV, along with a decrease in blood pressure (BP), at 8 weeks follow up in subjects with newly diagnosed, never-treated essential hypertension. 3. One hundred and fifty patients (84 men and 66 women; mean (+/-SD) age 48 +/- 10 years) with newly diagnosed essential hypertension were divided to five groups of 30 patients each to receive one of the following antihypertensive drugs (or drug combinations): 5 mg/day amlodipine; 50 mg/day atenolol; 5 mg/day enalapril; 25 mg/day hydrochlorothiazide; or a combination of 5 mg/day amlodipine and 50 mg/day atenolol. 4. The only significant change in HRV indices was an increase in total variability of RR intervals and an increase in high-frequency (HF) RR interval spectral power in the amlodipine + atenolol-treated group (P < 0.05). 5. The results indicate that there is a dissociation between changes in short-term HRV and mean RR interval and BP lowering in patients with newly diagnosed hypertension. 6. We interpret the increase in HF RR interval spectral power in the amlodipine + atenolol-treated group as being due to an increase in vagal modulation of RR intervals and/or diminution in sympathetic restraint of respiratory sinus arrhythmia.

Significance of bone marrow fibrosis in multiple myeloma.

AIMS: The aim of the current study was to asses the frequency of increased fibrosis in myeloma and to find its correlation with other bone marrow parameters and survival. METHODS: Forty-four multiple myeloma patients diagnosed between 2001 and 2005 were included in the present study. A detailed study of the bone marrow aspiration smears and trephine biopsy was done. Bone marrow fibrosis was graded and correlated with other parameters like plasma cell morphology, pattern of infiltration, mitotic activity and also with the survival of the patients. RESULTS: Increased fibrosis was seen in nine cases (20.5%). It was observed that plasma cell burden in the marrow was under-estimated in the aspirate smears compared with the trephine biopsy in patients with increased fibrosis. Increased marrow fibrosis correlated significantly with poorly differentiated plasma cell morphology (p = 0.020) and mitotic activity (p = 0.003), which by themselves are established prognostic markers for survival in multiple myeloma. Patients with increased fibrosis of the marrow also had a median survival time of just 11 months. CONCLUSIONS: A bone marrow trephine biopsy is essential in all cases of myeloma at diagnosis, as it helps identify a subset of myeloma patients with increased marrow fibrosis and poorer prognosis.

Role of bone marrow trephine biopsy in the diagnosis of marrow involvement in Hodgkin's disease.

Bone marrow involvement in Hodgkin's disease alters the stage and hence the prognosis and treatment modality. Seventy-six patients of biopsy proven Hodgkin's disease in whom a bone marrow aspiration and biopsy were done simultaneously at the time of diagnosis were included in the study. Bone marrow involvement was seen in 14 (18%) cases. All 14 cases were diagnosed on biopsy. Only one aspirate was suspicious of involvement. Rest was either diluted (28%) or was normal (64%). Eleven patients were upstaged from stage I, II and III to stage IV. All patients had cytopenia of one or more cell line. Increased fibrosis, necrosis and a polymorphic cellular infiltrate were associated findings in the marrow. We wish to highlight the importance of bone marrow trephine biopsy over aspirate in staging even clinically early stage Hodgkin's disease.