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RSV infection remains a serious threat to the children all over the world, especially, in the low-middle income countries. Vaccine delivery via the mucosa holds great potential for inducing local immune responses in the respiratory tract. Previously, we reported the development of highly immunogenic RSV virus-like-particles (RSV-VLPs) based on the conformationally stable prefusogenic-F protein (preFg), glycoprotein and matrix protein. Here, to explore whether mucosal delivery of RSV-VLPs is an effective strategy to induce RSV-specific mucosal and systemic immunity, RSV-VLPs were administered via the nasal, sublingual and pulmonary routes to BALB/c mice. The results demonstrate that immunization with the VLPs via the mucosal routes induced minimal mucosal response and yet facilitated modest levels of serum IgG antibodies, enhanced T cell responses and the expression of the lung-homing marker CXCR3 on splenocytes. Immunization with VLPs via all three mucosal routes provided protection against RSV challenge with no signs of RSV induced pathology.
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Anticuerpos Antivirales , Ratones Endogámicos BALB C , Infecciones por Virus Sincitial Respiratorio , Vacunas contra Virus Sincitial Respiratorio , Vacunas de Partículas Similares a Virus , Proteínas Virales de Fusión , Proteínas de la Matriz Viral , Animales , Infecciones por Virus Sincitial Respiratorio/prevención & control , Infecciones por Virus Sincitial Respiratorio/inmunología , Vacunas contra Virus Sincitial Respiratorio/inmunología , Vacunas contra Virus Sincitial Respiratorio/administración & dosificación , Ratones , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Vacunas de Partículas Similares a Virus/inmunología , Vacunas de Partículas Similares a Virus/administración & dosificación , Proteínas Virales de Fusión/inmunología , Proteínas Virales de Fusión/genética , Proteínas Virales de Fusión/administración & dosificación , Femenino , Proteínas de la Matriz Viral/inmunología , Proteínas de la Matriz Viral/administración & dosificación , Proteínas de la Matriz Viral/genética , Inmunidad Mucosa , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Virus Sincitial Respiratorio Humano/inmunología , Pulmón/virología , Pulmón/inmunología , Glicoproteínas/inmunología , Glicoproteínas/administración & dosificación , Administración a través de la Mucosa , Virus Sincitiales Respiratorios/inmunología , Linfocitos T/inmunologíaRESUMEN
Chikungunya virus (CHIKV) is responsible for incapacitating joint pains and is a significant health hazard in many countries. Though a definite need for a CHIKV vaccine is felt, long disappearance of CHIKV from circulation in humans has been a concern for vaccine development. Use of two separate pattern recognition receptor ligands has been shown to enhance immune response to the administered antigen. In addition, intradermal delivery of vaccine tends to mimic the natural mode of CHIKV infection. Therefore, in this study, we explored whether intradermal and intramuscular immunization with inactivated CHIKV (I-CHIKV) supplemented with dual pattern-recognition receptor ligands, CL401, CL413, and CL429, is an effective approach to enhancing antibody response to CHIKV. Our in vivo data show that I-CHIKV supplemented with these chimeric PRR ligands induces enhanced neutralizing antibody response after intradermal delivery, but is less efficient after intramuscular immunization. These results suggest that intradermal delivery of I-CHIKV with chimeric adjuvants is a possible way to elicited a better antibody response.
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Fiebre Chikungunya , Virus Chikungunya , Vacunas Virales , Humanos , Virus Chikungunya/fisiología , Ligandos , Anticuerpos Antivirales , Fiebre Chikungunya/prevención & control , Anticuerpos Neutralizantes , Adyuvantes InmunológicosRESUMEN
Various vaccines are under development to prevent chikungunya (CHIKV) infection. For the assessment of the CHIKV vaccine-induced antibody response, it is extremely important to understand antibody response after the infection has occurred. Previously, we assessed IgG response in samples from healthy donors using I-CHIKV and found that IgG1 was the predominant subclass induced after CHIKV infection followed by IgG4. However, IgG3 subclass induction is reported in serum samples from patients with acute CHIKV infection. Therefore, in this study, we evaluated serum/plasma from samples of patients with acute CHIKV infection for the presence of IgG and IgG subclasses against I-CHIKV and recombinant E2 protein (rE2). Out of 44 samples that were positive against I-CHIKV, 43 were found reactive against rE2. The positivity of IgG1 either alone or together with other IgG subclasses using I-CHIKV was 89% samples, while 86% samples were positive using rE2. High titers of IgG1 are obtained with I-CHIKV (67%), while raised IgG4 levels are detected using rE2p (72%) in the samples that are positive for both these subclasses. Testing of 22 samples for neutralizing antibodies revealed 100% IgG1 positivity and neutralizing antibodies in 21, 1 sample negative for both. Overall, these data will be useful in assessing IgG subclass-specific CHIKV neutralization and response after CHIKV immunization.
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Fiebre Chikungunya , Anticuerpos Neutralizantes , Ensayo de Inmunoadsorción Enzimática , Humanos , Inmunoglobulina G , Proteínas RecombinantesRESUMEN
Currently there is no clinically approved chikungunya virus (CHIKV) vaccine for immunization. Though definite need is felt, long disappearance of CHIKV has been a concern. Inactivated CHIKV (I-CHIKV) is an attractive antigen to develop effective vaccines within a short period of time. However, highly purified inactivated CHIKV do not contain necessary triggers for induction of robust antibody response. Monophosphoryl lipid A (MPLA) is a TLR4 ligand which is expressed on immune cells and is known to enhance immune response. Additionally, route of delivery also plays a critical role in modulating the immune response. Thus, antigen, adjuvant and route of delivery might modulate immune response if combined. Therefore in this study, we explored the immunogenicity of inactivated CHIKV-MPLA combination in mice after administration by intradermal or intramuscular route. Long term immune response study was also conducted by varying the antigen concentration and keeping the adjuvant concentration constant. Our study showed that the CHIKV-MPLA combination induced higher binding antibodies as well as neutralizing antibody titers as compared to unadjuvanted CHIKV. No difference in antibody titers was observed after delivery by either of the routes. However, difference in IFNγ and IL4 profiles was observed when a supernatant from stimulated splenocytes was analyzed. Taken together, these data show that both routes could be used for administration of the I-CHIKV-MPLA combination.
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Fiebre Chikungunya , Virus Chikungunya , Adyuvantes Inmunológicos , Animales , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Fiebre Chikungunya/prevención & control , Inmunoglobulina G , Lípido A/análogos & derivados , RatonesRESUMEN
Background & objectives: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) continues to be a devastating pandemic. This study was aimed at performance assessment of SARS-CoV-2 IgM and IgG ELISAs, and investigation of their utility for patient diagnosis and sero-epidemiologic investigations. Methods: Serum/plasma samples from COVID-19 patients or asymptomatic contacts (n=180) and healthy donors (n=90) were tested in parallel using two commercial IgM ELISAs (Erbalisa and Inbios), and four IgG ELISAs (Kavach, Euroimmun, Erbalisa and Inbios) along with an indigenous ß-propiolactone inactivated virus-based ELISA (IRSHA-IgG-ELISA). Plaque reduction neutralization test (PRNT) was used as reference test. Results: Among 180 COVID-19 patients, 125 tested positive by PRNT. Inbios-IgM-ELISA showed sensitivity (Se)/specificity (Sp)/positive predictive value (PPV)/negative predictive value (NPV) of 93.6/97.8/98.4/94.4 per cent in relation to PRNT, and performed better than Erbalisa-IgM-ELISA (Se: 48%, Sp: 95.6%, PPV: 95.2%, NPV: 65.2%). During the first week of disease, only 47.4 per cent of the COVID-19 patients tested IgM positive by Inbios-IgM-ELISA, detection improving at two weeks and beyond (~86-100%). Among IgG tests, Inbios-IgG-ELISA ranked first in terms of sensitivity (83.2%), followed by IRSHA (64.8%), Euroimmun (64%), Erbalisa (57.6%) and Kavach (56%) tests. For all IgG tests, sensitivity improved during the third (73.9-95.7%) and fourth week (100%) of illness. The specificity (96.7-100%) and PPV (96.2-100%) of all IgG tests were high; NPV ranged between 71.9 and 87.1 per cent with Inbios-IgG-ELISA scoring highest. Interpretation & conclusions: Our results show that IgM detection by the current, most sensitive ELISAs cannot replace molecular diagnosis, but may aid as a supplement test. The available IgG tests are suitable for serosurveys for the assessment of previous virus exposure.
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COVID-19 , SARS-CoV-2 , Anticuerpos Antivirales , Ensayo de Inmunoadsorción Enzimática , Humanos , Inmunoglobulina G , Inmunoglobulina M , Pruebas de Neutralización , Sensibilidad y EspecificidadRESUMEN
For the assessment of vaccine-induced immune response and to understand the role of antibodies in neutralization, it is necessary to assess dynamics of various antibodies in patients with different clinical manifestations. This study aims to quantitate circulating levels of IgA/IgG and IgG subtypes induced at different days postonset of symptoms, in severe and nonsevere patients. For this, serum or plasma samples (n = 146) collected from 79 COVID-19 patients were used. Indirect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific IgA, IgG, and IgG subtype specific enzyme-linked immunosorbent assays (ELISAs) were performed. Antibody titers between severe and nonsevere patients were compared at different times postonset of clinical symptoms. Titers in ELISA were compared to neutralizing antibody (Nab) titers determined by plaque reduction neutralization test (PRNT). Over 75% patients were positive for IgA/IgG antibodies in the first week. The ELISA titers did not differ during the first week; however, severe disease exhibited raised titers thereafter. Nab titers correlated with the ELISA titers in mild presentation but not in severe disease. IgA and IgG1 antibodies correlated stronger with Nabs. The findings highlighted that IgA together with IgG play an important in SARS-CoV-2 neutralization. These results will prove useful in assessing efficacy of vaccines and understanding disease pathogenesis.
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Anticuerpos Antivirales/sangre , COVID-19/inmunología , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , SARS-CoV-2/inmunología , Adolescente , Adulto , Anciano , Anticuerpos Neutralizantes/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas de Neutralización , Adulto JovenRESUMEN
In view of the rapidly progressing COVID-19 pandemic, our aim was to isolate and characterize SARS-CoV-2 from Indian patients. SARS-CoV-2 was isolated from nasopharyngeal swabs collected from the two members of a family without any history of (H/O) travel abroad. Both the virus isolates (8003 and 8004) showed CPE on day 3 post-inoculation, viral antigens by immunofluorescence assay and produced distinct, clear and uniform plaques. Infectious virus titers were 5 × 106 and 4 × 106 Pfu/ml by plaque assay and 107.5 and 107 by CPE-based TCID50/ml, respectively. Phylogenetic analysis grouped our isolates with the Italian strains. On comparison with Wuhan strain, 3 unique mutations were identified in nsp3 (A1812D), exonuclease (P1821S) of Orf1ab and spike protein (Q677H) regions, respectively. Both the viruses grouped with Italian strains of SARS-CoV-2 suggesting possible source being the virus imported from Italy. These fully characterized virus isolates will be useful in developing neutralization/virological assays for the evaluation of vaccines/antivirals.
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COVID-19/virología , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , Animales , Prueba de Ácido Nucleico para COVID-19 , Chlorocebus aethiops , Proteasas Similares a la Papaína de Coronavirus/genética , Exonucleasas/genética , Genoma Viral , Humanos , India , Mutación , Nasofaringe/virología , Filogenia , ARN Polimerasa Dependiente del ARN/genética , Glicoproteína de la Espiga del Coronavirus/genética , Viaje , Células Vero , Proteínas no Estructurales Virales/genética , Ensayo de Placa Viral , Secuenciación Completa del GenomaRESUMEN
Current chikungunya antibody prevalence and titers are likely to differ based on the exposure rates before the 2006 reemergence in India. For vaccine usage, such data are of immense importance. This study addresses age-stratified IgG titers and its subtypes in Pune, India, endemic for the disease. 170 age-stratified serum pools from 791 individuals with prior chikungunya exposure, and 15 samples from acute disease phase were analyzed. An indirect ELISA based on inactivated chikungunya virus was used to determine anti-CHIKV-IgG and its subtypes. Neutralizing antibody titers (plaque reduction neutralization test [PRNT]) were compared with binding antibody titers (ELISA). Anti-CHIKV-IgG titers along with IgG1 and IgG4 increased till the age-group of until 11-15 years and remained comparable thereafter till > 65 years. IgG1 was the predominant IgG subtype detected in all the pools, whereas IgG4 was present in 151/170 pools. Strong positive correlation of IgG1 was obtained with CHIKV-PRNT50 titers. None of the sample had anti-CHIKV-IgG2, whereas five pools had IgG3 antibody. In the acute-phase serum sample, IgG1 was present in all the samples, whereas IgG4 was present in 8/15 samples. IgG4 was predominant in four samples. During acute phase and at different times postinfection, IgG1 circulated in high titers followed by IgG4. Higher antibody titers in adults reflect reexposures. The data will prove useful in assessing immune response to CHIKV vaccine in relation to IgG subtype.
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Anticuerpos Antivirales/sangre , Fiebre Chikungunya/inmunología , Virus Chikungunya/inmunología , Inmunoglobulina G/sangre , Adolescente , Adulto , Factores de Edad , Anticuerpos Neutralizantes/sangre , Fiebre Chikungunya/sangre , Fiebre Chikungunya/epidemiología , Estudios Transversales , Ensayo de Inmunoadsorción Enzimática/estadística & datos numéricos , Femenino , Humanos , Inmunoglobulina M/sangre , India/epidemiología , Masculino , Persona de Mediana Edad , Pruebas de Neutralización/normas , Pruebas de Neutralización/estadística & datos numéricos , Adulto JovenRESUMEN
BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic caused by infection with severe acute respiratory syndrome - coronavirus-2 (SARS-CoV-2) continues to affect many countries and large populations. Serologic assays for antibody detection aid patient diagnosis and seroepidemiologic investigations. METHODS: An indirect IgG ELISA was developed indigenously using ß-propiolactone (BPL) inactivated SARS-CoV-2. This assay was used for screening 200 healthy donor sera collected prior to COVID-19 emergence (2017-2019), 185 serum/plasma samples of confirmed COVID-19 patients (nâ¯=â¯137) and 57 samples of viral RNA positive asymptomatic contacts (nâ¯=â¯51). The IgG response was studied in relation to duration and severity of illness. RESULTS: The ELISA demonstrated 97 % specificity and IgG detection in >50 %, 80 %, 93.8 % and 100 % of the patients respectively during the first, second, third and fourth week of illness. IgG detection rate was higher in patients with severe disease (SD, 90.9 %) than those with mild disease (MD, 68.8 %) during the second week of illness (Pâ¯=â¯0.027). IgG seropositivity among asymptomatic contacts was 64.7 %. IgG ELISA absorbance values were higher in SD than MD patients during the first 2 weeks of illness (Pâ¯<â¯0.05). No significant difference was observed between the absorbance values of asymptomatic subjects and MD patients (Pâ¯=â¯0.94). CONCLUSION: The BPL inactivated virus-based ELISA could detect IgG antibodies early and in a significant proportion of COVID-19 patients suggesting its potential utility as a supplement to the currently used viral RNA detection tests in patient diagnosis and contact screening algorithms.
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Prueba Serológica para COVID-19/métodos , COVID-19/diagnóstico , Inmunoglobulina G/sangre , Propiolactona/farmacología , SARS-CoV-2/inmunología , Anticuerpos Antivirales/sangre , COVID-19/sangre , COVID-19/patología , Ensayo de Inmunoadsorción Enzimática , Humanos , Sensibilidad y Especificidad , Estudios Seroepidemiológicos , Inactivación de Virus/efectos de los fármacosRESUMEN
Scalp avulsion is a rare but severe injury. It usually happens while using industrial or agriculture machinery. Scalp avulsion results from hair entrapment in a rotating machine. There are various options for treatment of scalp avulsion. Herein, the authors present a case of total scalp avulsion which was treated by multiple trephination technique using neurosurgical burr.
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Reimplantación , Cuero Cabelludo , Cabello , Humanos , Microcirugia , Cuero Cabelludo/cirugía , TrepanaciónRESUMEN
BACKGROUND: Dengue is a public health problem worldwide. Therapeutic monoclonal antibodies (MAbs) against dengue virus (DENV) are likely to be available soon. In view of the feasibility issues pertaining to pretreatment viraemia quantitation for therapy decisions, we conducted this study for investigation of a correlation between patient serostatus (NS1/immunoglobulin M [IgM]/IgG) and viraemia levels among Indian dengue patients at the time of first diagnosis. METHODS: The study included 297 serum samples from dengue patients in Pune, India. The samples were tested for NS1, IgM and IgG (capture enzyme-linked immunosorbent assay [ELISA] for identifying secondary dengue) using Panbio ELISAs. Quantitation of viraemia was conducted using an NS1 ELISA-based 50% tissue culture infectious dose (TCID50) test in Vero cells. RESULTS: Viraemia was detectable only among NS1-positive patients (n = 229, range 0.5-8.3 logTCID50/ml) with a mean titre of 1.9 logTCID50/ml. Among the NS1-positive patients, DENV titres were higher in IgM-negative than IgM-positive patients (p < 0.0001) and in primary (IgG < 18 Panbio units) versus secondary (IgG > 22 Panbio units) dengue patients (p = 0.002). Virus titres were higher during the first 3 days of illness and decreased later (p = 0.005). CONCLUSIONS: The study provides a range of infectious DENV titres in relation to serologic status among dengue patients in India. The data suggest the possibility of using serological markers (NS1/IgM) as a basis for treatment decisions.
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Virus del Dengue , Dengue , Animales , Anticuerpos Antivirales , Chlorocebus aethiops , Dengue/diagnóstico , Ensayo de Inmunoadsorción Enzimática , Humanos , Inmunoglobulina M , India/epidemiología , Sensibilidad y Especificidad , Células Vero , Proteínas no Estructurales Virales , ViremiaRESUMEN
Chikungunya (CHIKV) reemerged in India after a gap of 32 years, in 2005-2006 and has established endemicity in Pune. To assess the degree of CHIKV exposure, we estimated age-stratified prevalence of IgG antibodies to CHIKV in Pune population. This retrospective study utilized age-stratified serum samples collected from 15 wards of Pune in 2017 for dengue (DENV) virus study. Indirect anti-CHIKV-IgG ELISA was developed and used to test 1904 samples. Exposure to CHIKV and DENV was compared in the same population. CHIKV-specific plaque reduction neutralization test (PRNT) was employed to evaluate ELISA positivity and neutralizing potential of anti-CHIKV-IgG antibodies. Indirect ELISA showed 98.5% concordance with commercial ELISA. Seropositivity to CHIKV was 46.4%, one-third children < 15 years being antibody positive. A significant increase (45%, p = 0.026-0.038) was noted at 16-25 years and varied between 48 and 56% until the age 65. In elderly (65 + years), antibody positivity was reduced (41%, p = 0.01). In children, CHIKV-PRNT50 titers increased with age and remained comparable from the age group 11-15 until > 65. Exposure to DENV was higher than CHIKV. Lower exposure of children and elderly could be due to lesser exposure to the vectors. High prevalence of IgG antibodies needs to be addressed while planning vaccine studies for CHIKV.
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Fiebre Chikungunya/epidemiología , Virus Chikungunya/inmunología , Adolescente , Adulto , Factores de Edad , Anciano , Fiebre Chikungunya/sangre , Fiebre Chikungunya/virología , Niño , Preescolar , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulina G/sangre , India/epidemiología , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Prevalencia , Curva ROC , Estudios Retrospectivos , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Vaccination via the pulmonary route could be an attractive alternative to parenteral administration. Research towards the best site of antigen deposition within the lungs to induce optimal immune responses has conflicting results which might be dependent on the type of vaccine and/or its physical state. Therefore, in this study, we explored whether deep lung deposition is crucial for two different vaccines, i.e., influenza and hepatitis B vaccine. In view of this, influenza subunit vaccine and hepatitis B surface antigen were labeled with a fluorescent dye and then spray-dried. Imaging data showed that after pulmonary administration to mice the powders were deposited in the trachea/central airways when a commercially available insufflator was used while deep lung deposition was achieved when an in-house built aerosol generator was used. Immunogenicity studies revealed that comparable immune responses were induced upon trachea/central airways or deep lung targeting of dry influenza vaccine formulations. However, for hepatitis B vaccine, no immune responses were induced by trachea/central airways deposition whereas they were considerable after deep lung deposition. Thus, we conclude that deep lung targeting is not a critical parameter for the efficacy of pulmonary administered influenza vaccine whereas for hepatitis B vaccine it is.
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PEGylation is a promising approach to increase the residence time of antibody fragments in the lungs and sustain their therapeutic effects. However, concerns arise as to the potential pulmonary toxicity of antibody fragments conjugated to high molecular weight (HMW) polyethylene glycol (PEG), notably after repeated administrations, and the possibility of PEG accumulation in the lungs. The purpose of this proof-of-concept study is to give insights about the safety of lung administration of a Fab' anti-IL17A antibody fragment conjugated to two-armed 40â¯kDa PEG (PEG40). The presence of the PEG40 moiety inside alveolar macrophages remained stable for at least 24â¯h after intratracheal administration of PEG40-Fab' to mice. PEG40 was then progressively cleared from alveolar macrophages. Incubation of PEG40 alone with macrophages in vitro did not significantly harm macrophages and did not affect phagocytosis or the production of inflammatory markers. After acute or chronic administration of PEG40-Fab' to mice, no signs of significant pulmonary toxicity or inflammatory cell accumulation were observed. A vacuolization of alveolar macrophages not associated with any inflammation was noticed when PEG40, PEG40-Fab', or unPEGylated Fab' were administered. To conclude this preliminary proof of concept study, acute or repeated pulmonary administrations of PEGylated Fab' appear safe in rodents.
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Cervical sympathetic chain schwannoma (CSCS) is an extremely rare benign tumor, and it is a diagnostic challenge. We report a case of 45-year-old female who presented with a solitary right cervical swelling with clinical features of Horner's syndrome (HS). She was evaluated with computed tomography, magnetic resonance imaging, and angiography. Surgical excision of the lesion was performed, and the histological examination revealed the diagnosis of schwannoma. Herein, we review the presentation, imaging characteristics, and operative considerations of a patient with a large CSCS, presenting with HS.
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OBJECTIVE: To determine outcomes of spinal anesthesia (SA) in high-risk patients undergoing lumbar spine surgery in whom general anesthesia (GA) was contraindicated. METHODS: A retrospective study was conducted in Bansal Hospital, Bhopal, India. SA was achieved with a heavy spinal dose of bupivacaine administered in the sitting position. After assessing sensory level, patients were placed into prone position. Throughout surgery, hemodynamic parameters were monitored. At the end of surgery, patients were placed into supine position and taken out of the operating room for monitoring in the recovery room. Postoperatively, time spent in the postanesthesia care unit, hemodynamic changes, incidence of nausea and vomiting, urinary retention, spinal headache, analgesic use, regression of sensory block, and length of hospital stay were documented. Patient and surgeon satisfaction was also assessed. RESULTS: The study included 18 high-risk patients with lumbar spine disease. Twelve patients were classified as American Society of Anesthesiologists IV, and 6 were classified as American Society of Anesthesiologists III. Ten patients underwent microdiscectomy, and 8 patients underwent canal and lateral recess decompression. None of the patients had anesthetic or surgical complications. Postoperative pain relief was excellent. There were no incidences of postoperative vomiting or urinary retention. Only 2 patients (11.11%) developed nausea. Both surgeons and patients reported a high level of satisfaction. SA was 12% cheaper than general anesthesia. CONCLUSIONS: SA is a safe, reliable, and satisfactory alternative to general anesthesia in high-risk lumbar spine surgeries. Postoperative morbidity and mortality can be reduced by SA and spinal analgesia techniques. SA allows good perioperative hemodynamic stability. It is also more cost-effective.
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BACKGROUND: This prospective randomized controlled study compared the efficacy of an equiosmolar and isovolumetric dose of 3% hypertonic saline, 20% mannitol, and 10% mannitol plus 10% glycerol combination in reducing the raised intracranial pressure (ICP) in patients with severe traumatic brain injury (TBI). METHODS: A total of 120 patients of severe TBI with increased ICP were randomized to receive an equiosmolar and isovolumetric dose of 3% hypertonic saline, 20% mannitol, and 10% mannitol plus 10% glycerol combination at a defined infusion rate, which was stopped when ICP was <15 mm Hg. RESULTS: A total of 120 patients with severe TBI (aged >18 years, Glasgow Coma Scale ≤8, and had sustained elevated ICP of >20 mm Hg for more than 5 minutes) were randomized during the study. All data were presented as mean (minimum-maximum). A one-way analysis of variance test was used to analyze the effect across the treatment group, and Tukey's method was used for multiple comparisons. A paired t-test was employed to analyze the effect of the medication within each group. All 3 drugs decreased ICP below 15 mm Hg (P < 0.0001). The maximum change in ICP occurred after a bolus dose of 3% hypertonic saline followed by 10% mannitol plus 10% glycerol combination and then 20% mannitol (60% vs. 57% vs. 55%, respectively). Mean arterial pressure and cerebral perfusion pressure were increased after the bolus dose of study medications. Maximum changes occurred after infusion of 3% hypertonic saline followed by 10% mannitol plus 10% glycerol combination and 20% mannitol (P < 0.0349 and <0.0013, respectively). There was no statistically significant change in the hematocrit value noted after the bolus dose of any of the study medications. Serum sodium and osmolarity were raised significantly after the bolus dose of study medications. Maximum changes in serum sodium and osmolarity occurred after the bolus dose of 3% hypertonic saline. The mean dose required to reduce ICP below 15 mm Hg for 3% hypertonic saline: 1.4 mL/kg, for 10% mannitol plus 10% glycerine: 1.7 mL/kg, and for 20% mannitol: 2.0 mL/kg. The mean time required to reduce ICP below 15 mm Hg for 3% hypertonic saline: 16 minutes, for 10% mannitol plus 10% glycerine: 19 minutes, and for 20% mannitol: 23 minutes. The maximum change in the Glasgow Coma Scale occurred after the bolus dose of 3% hypertonic saline, followed by 10% mannitol plus 10% glycerol combination and then 20% mannitol. CONCLUSIONS: All 3 osmotic compounds exhibit comparable effectiveness in reducing ICP when a similar osmotic load is administrated, but 3% hypertonic saline appeared to be more effective followed by 10% mannitol plus 10% glycerol combination and 20% mannitol. A dose of 1.4 mL/kg can be recommended as an initial bolus dose for 3% hypertonic saline. Hypertonic saline can be recommended to treat patients with pretreatment hypovolemia, hyponatremia, or renal failure. There is no clear benefit compared with 20% mannitol in regard to neurologic outcome, even though there is a minor positive trend for 3% hypertonic saline and 10% mannitol plus 10% glycerol combination.
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Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Diuréticos Osmóticos/administración & dosificación , Glicerol/administración & dosificación , Manitol/administración & dosificación , Solución Salina Hipertónica/administración & dosificación , Adolescente , Adulto , Anciano , Quimioterapia Combinada , Humanos , Infusiones Intravenosas , Hipertensión Intracraneal/tratamiento farmacológico , Persona de Mediana Edad , Concentración Osmolar , Estudios Prospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
Administration of influenza vaccines via the respiratory tract has potential benefits over conventional parenteral administration, inducing immunity directly at the site of influenza exposure as well as being needle free. In this study, we investigated the suitability of Advax™, a stable particulate polymorph of inulin, also referred to as delta inulin, as a mucosal adjuvant for whole inactivated influenza vaccine (WIV) administered either as a liquid or dry powder formulation. Spray freeze-drying produced Advax-adjuvanted WIV powder particles in a size range (1-5⯵m) suitable for inhalation. The physical and biological characteristics of both WIV and Advax remained unaltered both by admixing WIV with Advax and by spray freeze drying. Upon intranasal or pulmonary immunization, both liquid and dry powder formulations containing Advax induced significantly higher systemic, mucosal and cellular immune responses than non-adjuvanted WIV formulations. Furthermore, pulmonary immunization with Advax-adjuvanted WIV led to robust memory B cell responses along with an increase of lung localization factors i.e. CXCR3, CD69, and CD103. A less pronounced but still positive effect of Advax was seen on memory T cell responses. In contrast to animals immunized with WIV alone, all animals pulmonary immunized with a single dose of Advax-adjuvanted WIV were fully protected with no visible clinical symptoms against a lethal dose of influenza virus. These data confirm that Advax is a potent mucosal adjuvant that boosts vaccine-induced humoral and cellular immune responses both in the lung and systemically with major positive effects on B-cell memory and complete protection against live virus. Hence, respiratory tract immunization, particularly via the lungs, with Advax-adjuvanted WIV formulation as a liquid or dry powder is a promising alternative to parenteral influenza vaccination.
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Adyuvantes Inmunológicos/administración & dosificación , Subtipo H1N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/administración & dosificación , Inulina/análogos & derivados , Vacunas de Productos Inactivados/administración & dosificación , Administración por Inhalación , Animales , Anticuerpos Antivirales/inmunología , Linfocitos B/efectos de los fármacos , Linfocitos B/inmunología , Femenino , Inulina/administración & dosificación , Ratones Endogámicos BALB C , Infecciones por Orthomyxoviridae/prevención & control , Mucosa Respiratoria/efectos de los fármacos , Mucosa Respiratoria/inmunología , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunologíaRESUMEN
Teratomas are germ cell tumors commonly composed of cell types derived from all of the three germ layers. Intracerebral teratomas typically present in midline or paraxial lesions located in the pituitary stalk or the pineal region. Teratoma in posterior fossa is a rare entity. We reported a case of midline posterior fossa mature teratoma in a 3-month-old child.
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OBJECTIVE: To evaluate the benefits of intraoperative autologous blood transfusion in intracranial procedures and to conserve precious homologous blood due to shortage of donor and associated complications. METHODS: This was a prospective study performed at Bansal Hospital, Bhopal. Predetermined autologous blood was collected in a well-labeled bag containing citrate phosphate dextrose adenine solution after induction of general anesthesia. Then appropriate amount of crystalloid solution was transfused in to the body. All collected autologous blood was transfused back to the patient at the end of the surgery or during the surgery if excessive blood loss occurred. Demographic data, hemodynamic changes (mean arterial pressure, heart rate) before and after donation, complications, and any additional homologous blood requirement were noted. Pre- and postoperative hemoglobin and hematocrit values were compared. RESULTS: In total, 32 patients were included in this study. In our study, mean age was 48.87 years; male-to-female ratio was 1:1.4. The mean amount of autologous blood collected was 461 mL, and the mean amount of blood loss during surgery was 1048 mL. In our study, there was no statistically significant difference was found in mean arterial pressure and heart rate before and after autologous blood collection (P > 0.05). When we compared pre- and postoperative mean hemoglobin and hematocrit levels, there was a statistically significant difference present (P < 0.05); this was due to the fact that many patients had meningiomas (15 of 32). Additional homologous blood was required only in 25% of cases (8/32). Of 8 patients, 5 were again cases of deep-seated meningiomas. No complications were observed during or after autologous blood collection. CONCLUSIONS: Autologous blood transfusion is a safe, effective, and affordable method of blood transfusion in patients undergoing intracranial surgery. Complications associated with homologous blood transfusion can be avoided with autologous blood transfusion.