Search PubMed⌕ Search

Biomedical subjects

M Joshi

Publications and source records attributed to M Joshi.

At least 37 records · Page 2Linked to original sources
PubMed2001

Impact of nosocomial infections in trauma: does age make a difference?

BACKGROUND: The effect of age and infection on outcome after trauma is unknown. We evaluated the incidence and impact that nosocomial infection (NI) and age have on morbidity and mortality. Several risk factors were identified and analyzed for correlation with infection. METHODS: Prospective data were collected on patients admitted for > or = 3 days over a 2-year period. Each patient was followed by an infectious disease specialist throughout their hospitalization. Centers for Disease Control and Prevention guidelines were used to diagnose infection. RESULTS: Of the 3,254 patients admitted, 88% were < 65 and 12% were > or = 65 years of age. Injury Severity Score was not significantly different (older vs. younger). Five hundred one (17.4%) of the younger patients developed an NI with a significantly higher hospital length of stay (LOS), intensive care unit (ICU) LOS, and mortality compared with the noninfected group. One hundred forty-seven (39%) of the older group developed an NI and also had significant increases in hospital LOS, ICU LOS, and mortality. Older infected patients had the highest hospital LOS, ICU LOS, and mortality. The greatest relative risk of mortality was demonstrated with the combination of increased age and NI. Once infected, however, younger patients with penetrating trauma had a greater relative risk of mortality in the group-specific comparison. Many risk factors were associated with infection. Only chronic obstructive pulmonary disease in elderly trauma patients was a significant independent risk factor for infection. CONCLUSION: NI significantly increases hospital LOS, ICU LOS, and mortality after injury. Age increases risk of infection matched for injury severity, with a significantly higher hospital LOS, ICU LOS, and mortality. Once infected, however, younger patients with penetrating trauma have the greatest risk of mortality. Chronic obstructive pulmonary disease in elderly trauma patients was found to be an independent predictor of infection.

Adult↗
PubMed2001

Systemic inflammatory response syndrome score at admission independently predicts infection in blunt trauma patients.

BACKGROUND: Systemic inflammatory response syndrome (SIRS) score has been demonstrated to be an accurate predictor of outcome in critical surgical illness. To our knowledge, there is a paucity of data using SIRS score as a tool to predict posttraumatic infection. Our goal was to determine whether the severity of SIRS score at admission is an accurate predictor of infection in trauma patients. METHODS: Prospective data were collected on 4,887 blunt trauma patients admitted to a primary adult resource center designated trauma center over an 18-month period. Patients were stratified by age and Injury Severity Score (ISS). SIRS score was calculated at admission. SIRS was defined as an SIRS score > or = 2. Each patient was screened for infection by an infectious disease specialist. Those at high risk for infection were then monitored daily throughout their hospitalization. Centers for Disease Control and Prevention guidelines were used to diagnose infection. RESULTS: Of the 4,887 patients, 1,850 (38%) were admitted > 24 hours and evaluated for subsequent infection (mean ISS, 16 +/- 9; mean age, 43 +/- 19, SD). Thirty-one percent (577) of the patients acquired an infection. The mean hospital length of stay (20.2 days vs. 6.5 days) and mortality (7.8% vs. 2.7%) were significantly greater in the infected group (p < 0.001). Of the four SIRS variables (temperature, heart rate, white blood cell count, and respiratory rate), hypothermia and leukocytosis were the most significant predictors of infection (p < 0.001) when adjusted for age and ISS. SIRS scores of > or = 2 were increasingly predictive of infection when analyzed by multiple logistic regression analysis. CONCLUSION: An admission SIRS score of > or = 2 is a significant independent predictor of infection and outcome in blunt trauma. Daily SIRS scores may be a meaningful method of assessing postinjury risk of infection, and may initiate earlier diagnostic intervention for determination of infection.

Adult↗
PubMed2001

Pulmonary disposition of budesonide from liposomal dry powder inhaler.

The Purpose of this study was to establish the use of a developed dry powder inhaler of budesonide liposomes in pulmonary drug delivery. Budesonide liposomes composed of egg phosphatidyl choline (EPC) and cholesterol were prepared using a lipid-film hydration technique. The liposomal dispersion was freeze dried and formulated to a dry powder inhaler. The entrapped drug values (91.79% to 78.99%) of freeze dried liposomes were estimated in prepared batches after purification from the free drug by centrifugation of the rehydrated vesicles. In vitro drug retention was evaluated using methanolic phosphate buffer saline and bronchoalveolar lavage, following incubation at 37 degrees C. All batches were found to retain more than 63.54% of budesonide within liposomes at the end of 24 h. Rehydrated budesonide liposomes or nonencapsulated budesonide was delivered to rat lungs by intratracheal administration. The pulmonary drug disposition was assessed by simultaneous monitoring of drug levels in the bronchoalveolar lavage and lung tissue. After intratracheal administration, cumulative drug levels in the lung tissue indicated that the targeting factor was at least 1.66 times higher in liposomes. The maximal drug concentration in the lung homogenate for the liposomal dry powder inhaler was 36.64 micrograms as compared to 78.56 micrograms with the plain drug. Similarly, the time for maximum drug concentration in the lung homogenate for the liposomal dry powder inhaler was 9-12 h as compared to 3 h for that of the plain drug. Hence, the use of a developed liposomal budesonide dry powder inhaler was found to provide desired drug levels in the lungs for a prolonged period of time, which is expected to enhance the therapeutic index of the drug and probably reduce the dose and cost of therapy as well.

Administration, Inhalation↗
PubMed2001

Group A Streptococcus (GAS) soft-tissue infections: a lethal organism on the rise.

Several reports over the past decade have suggested that there has been an increase in the number of invasive streptococcal infections with young children and the elderly being at the highest risk. We evaluated the incidence of group A Streptococcus (GAS) and compared it with historic data collected at our institution. Prospective data were collected on patients diagnosed with GAS (with and without shock) admitted to a tertiary-care center from July 1995 to July 2000. Each patient was followed by an infectious disease specialist throughout the hospital stay. Definitions of streptococcal toxic shock syndrome (STSS) developed by the Centers for Disease Control and Prevention were used. Thirty-eight patients (mean age of 39+/-12) presenting with GAS soft-tissue infections were admitted to our institution over a 5-year period (7.6 patients per year). Fourteen (37%) were diagnosed with STSS. This represents a greater than fourfold increase in the average number of cases per year of patients diagnosed with GAS and a nearly 4.5 times greater increase in the annual number of patients diagnosed with STSS. The overall mortality of patients diagnosed with GAS was 13 per cent, which increased to 36 per cent in patients diagnosed with STSS. We conclude that there has been a significant increase in the incidence of GAS soft-tissue infections over the past 5 years at our institution. This may represent a new virulent strain, as the majority of these infections did not occur in typical high-risk patients at the extremes of their lives. Further epidemiologic population-based studies are needed to further delineate the severe nature of this problem.

Adult↗
PubMed2000

Synthesis and construction of a novel multiple peptide conjugate system: strategy for a subunit vaccine design.

We describe the design and synthesis of a novel well characterized multi-peptide conjugate (MPC) system containing antigens from human malaria parasite and the Tat protein of HIV type-1 (HIV-1-Tat). Construction of the MPC utilizes Fmoc solid-phase peptide synthesis coupled with solution chemistry. In the first phase, a core template that serves as primary anchor for the synthesis and attachment of multiple antigens is synthesized. Serine(trityl) and multiple lysine branches with epsilon groups blocked during chain assembly are incorporated forming a tetrameric core. Cysteine whose side chain thiol serves to couple haloacetyl or S-protected haloacetyl peptides is added to complete assembly of the core template. Modification to the coupling solvent, addition of key amino acid derivatives (N-[1-hydroxy-4-methoxybenzyl]) in the peptide sequence allows the synthesis of base peptides on the core template with molecular mass greater than 7500 kDa. Base peptides are then reacted with high performance liquid chromatography purified haloacetyl peptides to generate multiple peptide conjugates with molecular masses of 10 to 13 kDa. MPC constructs thus formed are further characterized by matrix assisted laser desorption-time of flight mass spectroscopy (MALDI-MS), amino acid analysis, size exclusion chromatography, and SDS-polyacrylamide gel electrophoresis (PAGE). To our knowledge, this is the first report describing a chemically well defined multiple conjugate system with potential for development of synthetic subunit vaccines.

Amino Acid Sequence↗
PubMed2000

Community-acquired infections in the geriatric trauma population.

The incidence of community-acquired infections (CAs) and their relationship to the incidence of nosocomial infections (NI), to our knowledge, is unknown in elderly trauma patients. We prospectively collected data on 380 patients > or =65 years of age who were admitted >48 h to our trauma center over a 2-year period. One hundred seventy-seven patients (47%) developed an infection. A total of 147 (39%) patients were diagnosed with an NI, and 67 (18%) were diagnosed with a CA. Of the 67 patients with CA, 37 (55%) went on to develop an NI. Patients with the combination of CA and NI had the greatest mean ICU (28.6 days) and hospital length of stay (38.2 days). Mortality was increased significantly in patients with the combination of CA and NI (27%). Respiratory and genitourinary infections were the most common CA. Patients with respiratory CAs accounted for the greatest proportion of NIs. Thus, community-acquired and nosocomial infections significantly increase morbidity and mortality in elderly patients post-injury. Patients who present with a CA are at increased risk of acquiring an NI, which is associated with the most significant increase in length of stay and mortality.

Aged↗
PubMed2000

Risk factors for nosocomial pneumonia in critically ill trauma patients.

Nosocomial pneumonia is the most common pulmonary complication in trauma patients and the leading cause of death in nosocomial infections. A comprehensive review of pneumonia studies is provided. The Centers for Disease Control's nosocomial pneumonia pathogenesis model is reviewed and was used to guide the selection of risk factors evaluated in this study. The purposes of this research were to identify underlying dimensions (factors) of variables that increase the risk of nosocomial pneumonia and to identify predictors of nosocomial pneumonia in critically ill trauma patients.

Adult↗
PubMed1999

Brain segmentation and the generation of cortical surfaces.

This paper describes methods for white matter segmentation in brain images and the generation of cortical surfaces from the segmentations. We have developed a system that allows a user to start with a brain volume, obtained by modalities such as MRI or cryosection, and constructs a complete digital representation of the cortical surface. The methodology consists of three basic components: local parametric modeling and Bayesian segmentation; surface generation and local quadratic coordinate fitting; and surface editing. Segmentations are computed by parametrically fitting known density functions to the histogram of the image using the expectation maximization algorithm [DLR77]. The parametric fits are obtained locally rather than globally over the whole volume to overcome local variations in gray levels. To represent the boundary of the gray and white matter we use triangulated meshes generated using isosurface generation algorithms [GH95]. A complete system of local parametric quadratic charts [JWM+95] is superimposed on the triangulated graph to facilitate smoothing and geodesic curve tracking. Algorithms for surface editing include extraction of the largest closed surface. Results for several macaque brains are presented comparing automated and hand surface generation.

Algorithms↗
PubMed1999

Unusual radiological presentation and rapid fatal progression of invasive pulmonary aspergillosis in an immunocompetent young patient.

Invasive aspergillosis occurs very rarely in immunocompetent hosts. We describe a 21-year-old female with no obvious immunosuppression or underlying lung disease, who presented with minimal symptoms and bilateral hilar prominence on chest X-ray. Invasive aspergillosis was diagnosed on an open lung biopsy. She deteriorated in the ensuing 2 weeks and died of a sudden massive haemoptysis. This initial radiological abnormality and the rapid clinical course of the disease in young immunocompetent patients have not been previously reported.

Adult↗
PubMed1999

Piperacillin/tazobactam plus tobramycin versus ceftazidime plus tobramycin for the treatment of patients with nosocomial lower respiratory tract infection. Piperacillin/tazobactam Nosocomial Pneumonia Study Group.

An open-label, randomized, comparative, multi-centre study was conducted at 25 centres in the USA and Canada to compare the safety and efficacy of piperacillin/tazobactam plus tobramycin with ceftazidime plus tobramycin in patients with lower respiratory tract infections. Piperacillin/tazobactam (3 g/375 mg) every 4 h or ceftazidime (2 g) every 8 h were administered i.v. for a minimum of 5 days. Tobramycin (5 mg/kg/day) given in divided doses every 8 h was administered to all patients. Patients with Pseudomonas aeruginosa isolated from respiratory secretions at baseline were to continue tobramycin for the duration of the study. Tobramycin could be discontinued in other patients after the baseline culture results were known. A total of 300 patients was randomized, 155 into the piperacillin/tazobactam group and 145 into the ceftazidime group. Of these, 136 patients (78 in the piperacillin/tazobactam group and 58 in the ceftazidime group) were considered clinically evaluable. Both groups were comparable for age, sex, duration of treatment and other demographic features. The clinical success rate in evaluable patients was significantly greater (P = 0.006) in the piperacillin/tazobactam treatment group (58/78; 74%) than in the ceftazidime group (29/58; 50%). Eradication of the baseline pathogen was significantly greater (P = 0.003) in the piperacillin/tazobactam group (66%) than in the ceftazidime group (38%). The clinical and bacteriological responses of those patients with nosocomial pneumonia were similar to the overall results. Twelve (7.7%) piperacillin/tazobactam-treated patients and 24 (17%) ceftazidime-treated patients died during the study (P = 0.03). Seven of the 24 deaths in the ceftazidime treatment group but only one of the 12 deaths in the piperacillin/tazobactam treatment group were directly related to failure to control infection. The majority of adverse events were thought by the investigator to be attributable to the patients' underlying disease and not drug related. In this study, piperacillin/tazobactam plus tobramycin was shown to be more effective and as safe as ceftazidime plus tobramycin in the treatment of patients with nosocomial LRTI.

Adolescent↗
PubMed1999

L-arginine metabolites regulate DNA synthesis and nitric oxide synthase activity in cultured human dermal microvascular endothelial cells--potential positive and negative regulators of angiogenesis derived from L-arginine.

Human dermal microvascular endothelial cell (HDMVEC) growth and proliferation is important for skin angiogenesis. Our data support the hypothesis that a regulatory switch from an angiogenic to a nonangiogenic stimulus involves a change in l-arginine metabolism from polyamines (PAs) to nitric oxide (NO) and, conversely, a change to an angiogenic stimulus is expected to drive l-arginine metabolism in favor of PA synthesis. Current studies with cultured HDMVECs demonstrated that NO inhibited, whereas the PA putrescine stimulated DNA synthesis. The nitric oxide synthase (NOS) inhibitor NG-nitro l-arginine methyl ester stimulated DNA synthesis with a significant increase from control at 2.5 and 5 mM (p < 0.05); in contrast, the ornithine decarboxylase (ODC) inhibitor alpha-difluoromethyl ornithine (DFMO) inhibited DNA synthesis with a significant decrease from control at 19.65, 29.48, and 39.48 microM (p < 0.05). NO donors sodium nitroprusside dihydrate, S-nitroso-N-penicillamine, and l-hydroxy-2-oxo-3(3-aminopropyl)-3-propyl-triazine all inhibited DNA synthesis. There was a significant increase in NOS activity with DFMO treatment (p < 0.05) and a less pronounced decrease in NOS activity with direct PA treatment. In summary, NO and PAs are important mediators of HDMVEC growth and PAs downregulate NOS activity in these cells. NOS and ODC enzyme products may not only be important components in the regulation of angiogenesis in the skin but they may also regulate their own synthesis via feedback mechanisms.

Arginine↗
PubMed1998

The structure of the upper atmosphere of mars: In situ accelerometer measurements from mars global surveyor

The Mars Global Surveyor (MGS) z-axis accelerometer has obtained over 200 vertical structures of thermospheric density, temperature, and pressure, ranging from 110 to 170 kilometers, compared to only three previous such vertical structures. In November 1997, a regional dust storm in the Southern Hemisphere triggered an unexpectedly large thermospheric response at mid-northern latitudes, increasing the altitude of thermospheric pressure surfaces there by as much as 8 kilometers and indicating a strong global thermospheric response to a regional dust storm. Throughout the MGS mission, thermospheric density bulges have been detected on opposite sides of the planet near 90 degreesE and 90 degreesW, in the vicinity of maximum terrain heights. This wave 2 pattern may be caused by topographically-forced planetary waves propagating up from the lower atmosphere.

Journal Article↗
PubMed1998

Implications of calreticulin function in parasite biology.

Calreticulin (CR) is a Ca(2+)-binding, multifunctional protein. The amazing array of CR-associated functions range from intracellular activities in secondary messenger release, protein folding and the modulation of gene expression to potential interactions with host receptors and signaling machinery and recognition by the host immune system. The multifunctional nature of CR may impact upon the ability of cells to recognize extracellular stimuli and coordinate appropriate responses. Identification of CR isolated from parasites and the conservation of its functions suggests that investigations into the contributions of CR to various aspects of parasite biology should be undertaken because it may reveal information regarding parasite interaction with the host and how the parasite may modulate its response to the host.

Journal Article↗
PubMed1998

Reductions in hospital use from self management training for chronic asthmatics.

The purpose of this study was to assess the impact of asthma Self Management Training on the health status and resource use of patients with chronic asthma. The study consisted of a randomized control design of chronic asthmatic patients in a tertiary care center in India. The intervention group (153 patients) received four training sessions in addition to the regular care provided to the control group (150 patients). Health status and resource use were measured at baseline and over a one year follow-up period. The intervention group had significantly better health status (measured by breathing ability), fewer productive days lost, and lower resource use (hospitalizations and emergency room visits) than the control group. Total annual costs (direct and indirect) were also lower, though physician costs were not included in the assessment. Therefore, incorporation of asthma Self Management Training as part of clinical management of asthma can result in improvements in health status and reductions in hospital use.

Adolescent↗
PubMed1998

The diagnostic and therapeutic approach to lower respiratory tract infections in the neutropenic patient.

In the neutropenic host, the impaired inflammatory response diminishes the signs and symptoms of pulmonary infection, making diagnosis difficult. A practical approach to diagnosis and treatment in this population is to assess the radiographic appearance of infiltrates as localized (occurring as early, refractory or late phase), or diffuse; this approach is reviewed here.

Anti-Bacterial Agents↗
PubMed1998

Effect of prophylactic administration of recombinant human granulocyte colony-stimulating factor (filgrastim) on the frequency of nosocomial infections in patients with acute traumatic brain injury or cerebral hemorrhage. The Filgrastim Study Group.

OBJECTIVE: To determine whether the use of prophylactic recombinant human granulocyte colony-stimulating factor (filgrastim) reduces the frequency of nosocomial infections in patients with either acute traumatic brain injury or cerebral hemorrhage. DESIGN: Randomized, placebo-controlled, double-blind, multicenter phase II study. SETTING: Intensive care units of seven medical centers. PATIENTS: Patients with either acute traumatic brain injury or cerebral hemorrhage who were intubated within 6 hrs of admission and who were expected to be ventilated for >72 hrs. INTERVENTIONS: Patients were randomized to receive daily subcutaneous injections of placebo (n = 21) or one of two doses of filgrastim (75 microg [n = 20] or 300 microg [n = 20]) for 10 days or until the absolute neutrophil count was >75,000 cells/mm3 or until extubation. MEASUREMENTS AND MAIN RESULTS: End points included increase in absolute neutrophil count, safety of filgrastim, and frequency of nosocomial infections (pneumonia, bacteremia, and urinary tract infection). Filgrastim caused a dose-dependent increase in absolute neutrophil count. There were no differences in the frequency of pneumonia or urinary tract infection; however, there was a dose-dependent decrease in the frequency of bacteremias (p < .05). Adverse events were similar among the three groups. There was one case of acute respiratory distress syndrome in the placebo group. CONCLUSION: In this patient population, use of filgrastim was safe and the agent appeared to reduce the risk of primary bacteremias but had no beneficial effects on mortality, length of stay, or other nosocomial infections.

APACHE↗