Protective immunity to experimental tuberculosis by mannophosphoinositides of mycobacteria

Mannophosphoinositides isolated from mycobacterial cells were found to induce both humoral and cell-mediated immune responses in mice when injected as mannoside-methylated bovine serum albumin (MBSA) complexes. Immunization of mice with mannoside-MBSA complexes elicited significant protection against challenge with LD₅₀ dose of M. tuberculosis H₃₇Rv as revealed by high survival rate, low values of root-specific lung weight, lung densities and colony forming units recovered from lung, liver and spleen, compared to the nonimmunized group. These observations were further substantiated by histopathological studies. The protective immunity elicited by mannoside-MBSA complexes against challenge with M. tuberculosis H₃₇Rv was mediated by the cooperation of T-B cells, as shown by the passive transfer of immune cells/sera into syngeneic sublethally irradiated recipient mice.     

Primary myeloid sarcoma of the testicle with t(15;17)

The first case of acute promyelocytic leukemia presenting as a solitary testicular mass (myeloid sarcoma) that relapsed in the contralateral testicle is described. The neoplastic cells strongly expressed chloroacetate esterase, myeloperoxidase, CD33, CD43, and weakly, CD117. The presence of many azurophil granules and Auer rods was detected by electron microscopy. Translocation (15;17)(q22;q21.1) was revealed by cytogenetics and was verified by fluorescence in situ hybridization. Contralateral testicle is a favorite site for recurrence in a subset of testicular myeloid sarcomas. Subclassification of all cases of myeloid sarcoma ought to be attempted.     

Emergence of a nephropathogenic avian infectious bronchitis virus with a novel genotype in India

We describe the emergence of a nephropathogenic avian infectious bronchitis virus (IBV) with a novel genotype in India. The Indian IBV isolate exhibited a relatively high degree of sequence divergence with reference strains. The highest homology was observed with strain 6/82 (68%) and the least homology with strain Mex/1765/99 (34.3%).     

A monoclonal blocking EIA for herpes simplex virus type 2 antibody: validation for seroepidemiological studies in Africa

A competitive type-specific enzyme-linked immunosorbent assay (ELISA) for herpes simplex virus type 2 (HSV-2) antibody was developed using an infected cell antigen and a monoclonal antibody to glycoprotein G-2. This assay has been validated for use for epidemiological studies using a large panel of sera collected in rural Uganda and a panel of 143 sera characterised previously by Western blotting, the 'gold standard' for HSV type-specific serology. This evaluation was found to have a sensitivity of 96% and a specificity of 91% in comparison with Western blot on 143 sera from clinic patients. The ELISA had a sensitivity of 93% and a specificity of 91% in comparison with Western blot on 495 sera collected in Uganda. The assay showed good reproducibility and a low percentage of sera gave equivocal results, indicating its suitability for epidemiological studies.     

Surgery for infective endocarditis—analysis of factors affecting outcome

PurposeDespite advances in medical care, infective endocarditis (IE) has high mortality. Surgery for IE though recommended for complications of the disease is still not commonly offered due to conflicting reports in the literature. We reviewed our results of surgery for IE from the last 5 years to assess their outcome.MethodsA retrospective review from a single center of consecutive patients who underwent surgery for infective endocarditis from September 2014 to December 2019 was done. Data was collected from hospital records and follow-up done up to May 2020. Outcomes evaluated were mortality, follow-up survival, and postoperative complications. Factors affecting mortality and survival were analyzed.ResultsNinety-seven patients underwent surgery for IE during this period. Seventy-nine had native valve endocarditis (NVE) and 18 had prosthetic valve endocarditis (PVE). The overall postoperative mortality was 13%, with mortality for native valve endocarditis being 11% and that for prosthetic valve endocarditis being 22%, which was not statistically significant. Three-year survival for the overall group was 88.7% with 88.1% for NVE and 91.7% for PVE. Multivariate predictors of operative mortality were a high EuroSCORE II, diabetes mellitus, and the presence of Staphylococcus organism.ConclusionSurgery for infective endocarditis has a very acceptable early outcome and intermediate-term survival.     

A national cross-sectional survey of financial toxicity among bladder cancer patients

ObjectiveFinancial toxicity (FT) has been defined as the patient-level impact of the costs of cancer care. Our objective was to better characterize FT among bladder cancer patients as well as oncologic, demographic and insurance characteristics related to FT.MethodsWe conducted a cross-sectional survey of the Bladder Cancer Advocacy Network Patient Survey Network using the validated COST (COmprehensive Score for financial Toxicity) questionnaire. Our primary outcome was relative degree of FT, with lower COST scores corresponding to worse FT. Wilcoxon rank sum tests and multiple regression were used to evaluate differences in demographic, diagnostic and treatment characteristics as they related to degree of FT.ResultsAmong 226 patients, median age was 68 years with 64% male, 83% married, and 49% with Medicare with supplemental insurance. Respondents reported an average of 65 months since diagnosis, with 62% reporting noninvasive disease. Mean COST was 28.4 (range 0–44). On multivariable analysis, patients who were younger, with a household annual income less than $50,000, not retired, or with insurance that was neither Medicare nor employer paid were significantly more likely to have worse FT. A majority of respondents (63.5%) agreed or strongly agreed that they would be interested in discussing cost in the context of their treatment preferences, independent of COST score (P = 0.24).ConclusionsA national cross-sectional survey demonstrated high prevalence of FT which was worse among younger patients with lower incomes, not retired, and without employer-paid or Medicare insurance. Most patients preferred to discuss treatment costs with their bladder cancer provider.     

pH-adjusted periocular anaesthesia for primary vitreoretinal surgery

PURPOSE: To evaluate the efficacy of pH-adjusted bupivacaine in conjunction with medial orbital periconal block (periocular anaesthesia). METHODS: Sixty consecutive patients undergoing primary vitreoretinal surgery were enrolled prospectively. RESULTS: Adequate anaesthesia and akinesia with no intraoperative supplementation was achieved in 53 eyes (88.3%). Factors influencing intraoperative supplementation were combined vitrectomy with scleral buckling (p = 0.005) and duration of surgery of more than 2 hours (p = 0.001). No ocular or systemic complication resulted. CONCLUSION: pH-adjusted periocular anaesthesia is safe and effective in patients undergoing primary vitreoretinal surgery.     

ATP-Dependent colchicine transport by human erythrocyte glutathione conjugate transporter

We have recently demonstrated mutually inhibitory ATP-dependent transport of dinitrophenyl-S-glutathione (DNP-SG) and doxorubicin by DNP-SG ATPase purified from human erythrocyte membranes (S. Awasthi et al., 1998a,b). Our previous studies indicate a broad substrate specificity for this transport mechanism, including some P-glycoprotein substrates. Present studies were carried out to determine whether colchicine (COL), a classical P-glycoprotein substrate, could be transported by purified human erythrocyte DNP-SG ATPase reconstituted in artificial liposomes. We also investigated whether leukotriene C4 (LTC4), an endogenous proinflammatory glutathione-conjugate derived from arachidonic acid, would inhibit colchicine transport. Uptake of COL was compared in proteoliposomes reconstituted with the purified DNP-SG ATPase as well as control liposomes in the presence or absence of ATP. Increased colchicine uptake was observed upon addition of ATP to proteoliposomes, but not control liposomes. Uptake was linear with respect to the amount of vesicle protein used. Sensitivity to osmolarity was consistent with intravesicular COL accumulation. The ATP-dependent colchicine uptake was sensitive to temperature in a manner consistent with a protein-mediated transport process with activation energy of 7.3 kcal/mol. Time-dependent COL uptake by proteoliposomes in the presence of ATP was consistent with a single compartment model with an apparent rate constant of 0.21 +/- 0.02 min-1. Kinetic studies indicated a saturable behavior with respect to ATP (Km 2.3 +/- 0.7 mM) and colchicine (Km 4.3 +/- 0.2 microM). LTC4 was found to be a competitive inhibitor of COL transport (Kis 16.4 microM). Since DNP-SG ATPase is present in many tissues, it may play an important role in determining colchicine accumulation in cells. Increased LTC4 would tend to increase cellular COL accumulation.     

Multiparameter assessment of the cell cycle effects of bioactive and cytotoxic agents.

This paper describes the use of the bromodeoxyuridine/propidium iodide method to assess the effects of bioactive and cytotoxic agents on the kinetic characteristics of acute myelogenous leukemia cells. By careful selection of gates, the following parameters can be measured simultaneously using only 50,000 cells: the proportion of cells in S-phase, the distribution of cells within the S-phase compartment, the relative rate of DNA synthesis, the relative distribution of S-phase times, the proportion of S0 cells, and the proportion of cells in G1 and G2/M. This method was used to demonstrate that while retinoic acid, alpha-interferon, and cytosine arabinoside may all "inhibit" DNA synthesis, the actual effects of these agents differ. Retinoic acid appears to arrest cells in G1 without affecting the rate of DNA synthesis, while alpha-interferon and cytosine arabinoside "inhibit" DNA synthesis by reducing the rate of synthesis per se.