Platelet Indices as a Marker of Severity in Non-diabetic NonHypertensive Acute Ischemic Stroke Patients.

BACKGROUND: Platelet activation & aggregation are critical in pathogenesis of acute ischemic stroke. Mean platelet volume (MPV) & Platelet distribution width (PDW) are markers & determinants of platelet function. Larger platelets are metabolically more active, produce more prothrombotic factors, aggregate more easily & act as index of homeostasis and its dysfunction thrombosis. MATERIAL: We studied 70 non diabetic non hypertensive ischemic stroke patients without previous thrombotic events & not on anti platelet medications within 24 hour of onset of symptoms & compared with equal number of age and sex matched controls. Severity of stroke was calculated by Canadian neurological scale (CNS).Platelet indices were obtained from SYSMEX KX-21. OBSERVATION: Mean age of patients was 55 ± 7.11 and of controls was 52 ± 5.37. According to CNS patients were divided in two groups; with comprehension deficit (1st group, 32 patients) & without comprehension deficit (2nd group, 38 patients).Mean value for PDW & MPV in 1st group was 18.675 ± 3.494 & 12.894 ± 1.270 respectively and in 2nd group was 18.62 ± 3.387 & 12.42 ± 0.984 respectively and was significantly higher than mean value of 15.694 ± 3.127 & 10.46 ± 1.273 of PDW & MPV respectively in controls. In both study groups PDW & MPV was found to be significantly associated with severity of motor deficit. CONCLUSION: In patients of ischemic stroke platelet indices may be used for predicting severity of motor deficit. Although larger sample size and multivariate analysis is required before this can be used regularly in clinical practice.

Distribution and determinants of cytomegalovirus induced end organ disease/s among people living with HIV/AIDS in a poor resource setting: observation from India.

BACKGROUND: In India, despite well-established anti-retroviral treatment programs, Cytomegalovirus (CMV) infection-related end-organ diseases (EODs) still remain a major concern resulting in exacerbation of morbidity and mortality among HIV/AIDS patients. A prospective study was designed to understand the distribution and prognosis of CMV associated EODs and to determine a standardized cut-off value for serum CMV viral load associated with the development of EODs amongst HIV/AIDS subjects. METHODS: In a cohort of 400 late-diagnosed HAART naïve HIV/AIDS subjects attending anti-retroviral centers of Kolkata during 2008-2014, the median duration of follow-up was 560 days, and at least 3 visits subsequent to the baseline were mandatory for eligibility. HIV-1 and CMV viral load were estimated by performing Real-Time Polymerase Chain Reactions (PCR). RESULTS: Among subjects, 40.5% (162/400) had CMV EODs which were more common at lower CD4 counts. Poor prognosis and higher death rate were associated with a low CD4 count and increased HIV-1 and CMV viral loads. Subjects having higher CD4 count responded better to therapy [for CD4 = 60-100: Risk Ratio:RR = 1.48 (95% Confidence Interval: 95%CI = 1.18-1.82) and for CD4 = 30-59: RR = 1.64 (95%CI = 1.18-2.27)]. The cut off value of the serum CMV viral load (expressed as log10DNA/ml serum) associated with the development of EODs and disseminated CMV EODs was determined as 5.4 (p<0.0001) and 6.4 (p<0.0001) respectively. These cut offs were found to have satisfactorily high sensitivity, specificity, positive and negative predictive values. CONCLUSION: Prognosis of CMV EOD was poor as indicated by higher death rates among subjects with lower CD4 count, and specific cut-off values were found to have useful potential for identification and treatment of CMV infected HIV/AIDS patients in due time to avoid CMV EODs among HIV/AIDS subjects. Targeted intervention programs seemed to be required urgently to make these cut-offs operational in order to minimize the burden of CMV EOD in this vulnerable population.

Parenteral pentazocine and diabetes mellitus: a double whammy for cutaneous complication.

Pentazocine, a non-narcotic analgesic, though has no addictive potential but abused frequently via parenteral route for its psychological dependence. It causes local sclerosis resulting in non-healing ulcer at injection sites. Diabetes mellitus suppress host immunity, making them vulnerable to various bacterial skin and soft tissue infection among which mkethicillin resistant staphylococcus aureus (MRSA) infection are predominant. We report a case, a 50-year-old shopkeeper who used to inject pentazocine primarily as analgesic, later became addicted to it. Blindly injecting the drug in any approachable soft tissue resulted in woody induration of local skin with multiple ulcers in his both arms. He later developed type 2 Diabetes mellitus which made the scenario even worser.

Unravelling the Gordian knot: diagnostic dilemma in an HIV-positive patient with neurological involvement.

We report a case of a 40-year-old seropositive-HIV patient with a CD4 count of 120 who presented with fever, severe headache and neck stiffness. Suspecting a case of tubercular meningitis (TBM; as tuberculosis is the commonest opportunistic infection in HIV/AIDS patients in India), a lumbar puncture was performed and a cerebrospinal fluid study revealed TBM. The patient was started on combination antitubercular drug therapy from directly observed treatment, short course (DOTS) (Cat 1 regimen) along with pyridoxine 40 mg/day and adjunctive corticosteroid therapy. However, despite adequate antitubercular therapy for 4 weeks, the patient did not show any improvement in his clinical condition. On the contrary, in the process he developed cytomegalovirus (CMV) retinitis. So we question our learned readers if the coinfection of Mycobacterium tuberculosis and CMV should be implicated for the failure to respond to isolated antitubercular therapy contrary to our expectation.

Assessment of efficacy of pamidronate in undifferentiated spondyloarthropathy (uSpA): a placebo control trial in a tertiary level center.

Undifferentiated spondyloarthropathy (uSpA) is a nonspecific form of spondyloarthropathy where nonsteroidal anti-inflammatory drugs (NSAIDs) and disease-modifying anti-rheumatic drugs are still mainstay of treatment. We evaluated the efficacy and adverse effect profile of pamidronate, in uSpA patients refractory to NSAIDs therapy. A case series of 87 patients fulfilling the modified Amor criteria for the diagnosis of uSpA, having active disease even after 3-month continuous therapy with two NSAIDs, were selected. Active disease was defined as a VAS score >50 in a scale of 0-100 in 3 out of four following parameters: patients' global assessment, pain, BASFI and BASDAI morning stiffness. Sixty-six patients among those were administered monthly pamidronate infusion (60 mg over 4 h in 500 ml of normal saline) for 6 months. Other 21 patients (placebo group) transfused with normal saline. Treatment outcome was assessed by comparing baseline and 6 months value of BASDAI, BASFI, BASMI, BAS-G, CRP and ESR in both groups and improvement by ASAS-20 and BASDAI-50. Among the 66 patients, 48 patients (72.73%) achieved ASAS-20 and 42 patients (63.64%) achieved BASDAI-50 response. Among the treatment group, mean ESR, CRP, BASDAI, BASFI, BAS-G and BASAMI reduced by 54.81 mm/h (64.95%), 3.94 mg/l (43.3%), 3.74 (48.38%), 3.73 (49.40%), 4.47 (58.97%) and 4.28 (58.15%), respectively, after treatment, whereas in placebo group, increased by 5.48 mm/h (6.34%), 0.34 mg/l (3.77%), 0.24 (3.02%), 0.45 (6.03%), 0.05 (0.67%) and 0.52 (7.13%), respectively, after 6 months. Intravenous pamidronate has very good efficacy for the treatment of uSpA.

Incidence and risk factors of immune reconstitution inflammatory syndrome in HIV-TB coinfected patients

Tuberculosis is one of the leading causes of development of Immune reconstitution inflammatory syndrome (IRIS) in HIV patients receiving antiretroviral therapy (ART). OBJECTIVE: To determine the incidence of IRIS in HIV-TB coinfected patients, and to find out the possible risk factors associated with IRIS. MATERIALS AND METHODS: Study commenced with 96 patients adhered to standard antitubercular therapy (ATT) and ART without defaultering, and followed up for six months. RESULT: The mean (± SD) CD4 count and CD4 percentage at baseline was 59.16 (± 24.63) per mm³ and 4.59 percent (± 1.73) respectively. Only 18.75 percent developed IRIS after 57.05 (± 14.12) days of initiation of ART. Extrapulmonary tuberculosis was the most significant factor associated with IRIS (83.33 percent) than those without IRIS (44.87 percent) (p = 0.0032). Specifically, tubercular lymphadenitis (38.88 percent, p = 0.0364) and disseminated tuberculosis (33.33 percent, p = 0.0217) were significantly associated with IRIS. The other risk factors associated with appearance of IRIS were higher CD4 count (p = 0.0212) at three months after initiation of ART and increment of CD4 count (p = 0.0063) and CD4 percentage (p = 0.0016) during this period. The major manifestations of IRIS were fever (40 percent), followed by lymphadenitis (38 percent). The mortality rate in IRIS was not higher than those without IRIS. CONCLUSION: Patients with extrapulmonary tuberculosis, especially tubercular lymphadenitis, were more likely to develop IRIS and fever was associated in most of them. Higher increment of CD4 count may indicate development of IRIS in presence of new or worsening tuberculosis lesion.

Incidence and risk factors of immune reconstitution inflammatory syndrome in HIV-TB coinfected patients.

UNLABELLED: Tuberculosis is one of the leading causes of development of Immune reconstitution inflammatory syndrome (IRIS) in HIV patients receiving antiretroviral therapy (ART). OBJECTIVE: To determine the incidence of IRIS in HIV-TB coinfected patients, and to find out the possible risk factors associated with IRIS. MATERIALS AND METHODS: Study commenced with 96 patients adhered to standard antitubercular therapy (ATT) and ART without defaulting, and followed up for six months. RESULT: The mean (± SD) CD4 count and CD4 percentage at baseline was 59.16 (± 24.63) per mm³ and 4.59% (± 1.73) respectively. Only 18.75% developed IRIS after 57.05 (± 14.12) days of initiation of ART. Extrapulmonary tuberculosis was the most significant factor associated with IRIS (83.33%) than those without IRIS (44.87%) (p = 0.0032). Specifically, tubercular lymphadenitis (38.88%, p = 0.0364) and disseminated tuberculosis (33.33%, p = 0.0217) were significantly associated with IRIS. The other risk factors associated with appearance of IRIS were higher CD4 count (p = 0.0212) at three months after initiation of ART and increment of CD4 count (p = 0.0063) and CD4 percentage (p = 0.0016) during this period. The major manifestations of IRIS were fever (40%), followed by lymphadenitis (38%). The mortality rate in IRIS was not higher than those without IRIS. CONCLUSION: Patients with extrapulmonary tuberculosis, especially tubercular lymphadenitis, were more likely to develop IRIS and fever was associated in most of them. Higher increment of CD4 count may indicate development of IRIS in presence of new or worsening tuberculosis lesion.

Drug susceptibility profile of Mycobacterium tuberculosis isolated from HIV infected and uninfected pulmonary tuberculosis patients in eastern India.

HIV is driving the tuberculosis (TB) epidemic in many developing countries including India. This study was initiated to determine the drug resistance pattern of pulmonary TB among 200 HIV seropositive and 50 HIV negative hospitalized patients from different states of Eastern India. The TB positive isolates (120) were screened and characterized by conventional laboratory methods followed by first- and second-line drug susceptibility testing on Lowenstein-Jensen medium by the proportion method. The drug susceptibility testing showed 17.7% (16/90) and 6.6% (2/30) multidrug-resistant (MDR) TB for the HIV positive and HIV negative patients, respectively. 22.2% (4/18) of the isolated MDR-TB cases could be classified as extensively drug-resistant (XDR) TB isolates. 88.8% (16/18) of all the MDR-TB isolates and all XDR-TB isolates were screened from HIV patients. Five (27.7%) of the 18 MDR-TB isolates showed resistance to all the first-line drugs. Mortality rate among the XDR-TB isolates was as high as 75% (3/4). Patients with interrupted anti-TB drug treatment were the ones most affected. These findings are critical and the risk to public health is high, particularly with HIV infected patients.

A rapid immunochromatographic assay for the detection of Mycobacterium tuberculosis antigens in pulmonary samples from HIV seropositive patients and its comparison with conventional methods.

As tuberculosis generates a highly heterogeneous antibody repertoire, its diagnosis requires tests based on cocktails of antigens. We describe a new, rapid method called rapid immunochromatographic assay (RICA) for cocktail-based diagnosis, which can detect Mycobacterial antigens in sputum specimens. Six antigenic fractions of pathogenic Mycobacterium tuberculosis were used in combination as the capture antigens in the control line of the flow-through assay. Antigen detection of 200 sputum samples from HIV seropositive patients by RICA assay gave a sensitivity of 97.9%, specificity of 99.0%, positive predictive value of 98.9%, negative predictive value of 98.0%, false positive rate of 0.9%, false negative rate of 2.0%, prevalence rate of 49%, likelihood ratio for positive results 97 and likelihood ratio for negative results 0.02. The combination of RICA and AFB staining gave a sensitivity of 100%, specificity of 100%, positive predictive value of 100%, negative predictive value of 100%, false positive rate of 0%, false negative rate of 0%, likelihood ratio for negative results 0. The assay was simple, rapid and economical for the detection of M. tuberculosis infection and suitable for large scale screening of samples in endemic areas without any sophisticated equipment. The results of the assay proved to be superior to conventional methods and combined with clinical data, could form the basis for starting an earlier course of treatment.

Leishmanial lipid suppresses tumor necrosis factor alpha, interleukin-1beta, and nitric oxide production by adherent synovial fluid mononuclear cells in rheumatoid arthritis patients and induces apoptosis through the mitochondrial-mediated pathway.

OBJECTIVE: Leishmanial lipid is a strong immunosuppressor of host cells. Inhibition of the inflammatory responses of synovial cells through induction of apoptosis is one of the main targets of therapeutic intervention in rheumatoid arthritis (RA). This study was undertaken to examine the antiinflammatory and apoptosis-inducing effects of leishmanial lipid on adherent synovial fluid mononuclear cells (SFMCs) in patients with RA. METHODS: Lipid was extracted from a Leishmania donovani promastigote (MHO/IN/1978/UR6) by the Bligh and Dyer method. Nitric oxide (NO) was measured using the Griess reaction, and enzyme-linked immunosorbent assays for cytokines, NF-kappaB, and cytochrome c were performed. Levels of cytokines, inducible nitric oxide synthase, caspases, Bcl-2, Bax, t-Bid, and cytochrome c in the cell lysate and of NF-kappaB p65 in the nucleus were determined by Western blotting. Microscopic analysis, nuclear staining, DNA fragmentation assay, fluorescence-activated cell sorting, colorimetric assay for caspases, and fluorescent probe for measurement of mitochondrial membrane potential were used to study the leishmanial lipid-induced apoptotic pathway in SFMCs. RESULTS: Leishmanial lipid inhibited the release of tumor necrosis factor alpha, interleukin-1beta, and NO in the culture, decreased their cytosolic protein levels, and decreased NF-kappaB p65 levels in SFMCs, in a dose-dependent manner. It had the reverse effect on interleukin-10 levels. Leishmanial lipid-induced apoptosis involved the activation of caspase 3, caspase 9, and Bax, the release of cytochrome c, the alteration of mitochondrial membrane potential, and the down-regulation of Bcl-2. CONCLUSION: These results suggest that leishmanial lipid has strong antiinflammatory and apoptosis-inducing effects on SFMCs from patients with RA, and that apoptosis occurs via the mitochondrial pathway.

Current trends of opportunistic infections among HIV-seropositive patients from Eastern India.

In this report we describe the clinical and laboratory profiles of different opportunistic infections (OIs) among 125 immunocompromised patients admitted to a referral hospital in the eastern part of India. Different pathogens were isolated, identified and characterized using the laboratory gold standard methods. Oral candidiasis (88%) was found to be the most common OI, followed by tuberculosis (57%), enteropathogenic Vibrio (47%), cytomegalovirus infection (45%), cryptosporidial diarrhea (43%), Escherichia coli infection (42%) and other infections among the study subjects. Statistical analysis of the case studies shows 120/cumm median CD4+ blood cell count, and the OIs showed an inversely proportional occurrence to the CD4+ count of the immunocompromised patients. The spectrum and frequency of certain OIs highlight the urgency of studying HIV/AIDS in resource-limited countries where locally specific disease patterns may be observed. The purpose of the present investigation was the identification of such opportunistic pathogens, as we feel the HIV epidemic can be more effectively managed if physicians and health planners are aware of this information.