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Biomedical subjects

Nalini Singh

Publications and source records attributed to Nalini Singh.

14 recordsLinked to original sources
PubMed2006

Continuous delivery of human type I interferons (alpha/beta) has significant activity against acute myeloid leukemia cells in vitro and in a xenograft model.

In this study, we focused primarily on the antileukemic activity of interferon-beta (IFN-beta) in a murine xenograft model of acute myeloid leukemia (AML). Bolus administration of recombinant IFN-beta via the subcutaneous or intravenous route failed to show efficacy in mice injected with AML cells despite achieving peak plasma IFN-beta levels of more than 200 IU/mL. In contrast, stable expression of IFN-beta following adeno-associated virus (AAV) vector-mediated gene transfer resulted in significant antileukemic activity against primary AML cells derived from patients with poor prognostic markers. An almost linear relationship was observed with stable plasma levels of IFN-beta and antileukemic activity in mice. Even levels below 10 IU/mL were able to reduce tumor load by 50-fold when compared with control animals. These levels of IFN-beta are likely to be nontoxic in humans. Therefore, approaches capable of maintaining stable plasma levels of IFN-beta merit further clinical evaluation in patients with AML.

Acute Disease↗
PubMed2006

Human mesenchymal stem cells (hMSCs) expressing truncated soluble vascular endothelial growth factor receptor (tsFlk-1) following lentiviral-mediated gene transfer inhibit growth of Burkitt's lymphoma in a murine model.

BACKGROUND: Efficient gene transfer to bone marrow derived mesenchymal stem cells (MSC) would provide an important opportunity to express potent anticancer agents in the tumour microenvironment because of their contribution to the tumour stroma. METHODS: HIV-based lentiviral vectors were pseudotyped with four different envelope proteins; amphotropic murine leukaemia virus (ampho), murine leukaemia virus (10A1), feline endogenous virus (RD114), and the vesicular stomatitis virus glycoprotein (VSVG). These pseudotypes were examined for transduction efficiency in human bone marrow derived MSC. The effect of lentiviral expression of truncated soluble vascular endothelial growth factor decoy receptor (tsFlk-1) in MSC on growth of Raji cells was determined, both in vitro and in vivo. RESULTS: All lentiviral vectors produced significant levels of transduction at an multiplicity of infection (MOI) of 1, those bearing the RD114 envelope glycoprotein consistently produced higher transduction levels (mean 70 +/- 6%) compared with the other pseudotyped lentiviral vectors, although there was significant inter-donor variation. Stable transgene expression was achieved after multiple rounds of transduction with VSVG-pseudotyped particles, without alteration in the differentiative capacity of transduced cells. Co-injection of MSC stably expressing tsFlk-1 with Raji Burkitt's lymphoma cells significantly impaired subcutaneous tumour growth in immunodeficient mice when compared to controls where either unmanipulated MSC or GFP-expressing MSC were used. CONCLUSIONS: Human MSC are easily transduced by pseudotyped lentiviral particles but there is inter-donor variation in transduction efficiency. Gene-modified MSC expressing a gene of therapeutic potential can moderate growth of haematological malignancies.

Animals↗
PubMed2005

Preventing foot ulcers in patients with diabetes.

CONTEXT: Among persons diagnosed as having diabetes mellitus, the prevalence of foot ulcers is 4% to 10%, the annual population-based incidence is 1.0% to 4.1%, and the lifetime incidence may be as high as 25%. These ulcers frequently become infected, cause great morbidity, engender considerable financial costs, and are the usual first step to lower extremity amputation. OBJECTIVE: To systematically review the evidence on the efficacy of methods advocated for preventing diabetic foot ulcers in the primary care setting. DATA SOURCES, STUDY SELECTION, AND DATA EXTRACTION: The EBSCO, MEDLINE, and the National Guideline Clearinghouse databases were searched for articles published between January 1980 and April 2004 using database-specific keywords. Bibliographies of retrieved articles were also searched, along with the Cochrane Library and relevant Web sites. We reviewed the retrieved literature for pertinent information, paying particular attention to prospective cohort studies and randomized clinical trials. DATA SYNTHESIS: Prevention of diabetic foot ulcers begins with screening for loss of protective sensation, which is best accomplished in the primary care setting with a brief history and the Semmes-Weinstein monofilament. Specialist clinics may quantify neuropathy with biothesiometry, measure plantar foot pressure, and assess lower extremity vascular status with Doppler ultrasound and ankle-brachial blood pressure indices. These measurements, in conjunction with other findings from the history and physical examination, enable clinicians to stratify patients based on risk and to determine the type of intervention. Educating patients about proper foot care and periodic foot examinations are effective interventions to prevent ulceration. Other possibly effective clinical interventions include optimizing glycemic control, smoking cessation, intensive podiatric care, debridement of calluses, and certain types of prophylactic foot surgery. The value of various types of prescription footwear for ulcer prevention is not clear. CONCLUSIONS: Substantial evidence supports screening all patients with diabetes to identify those at risk for foot ulceration. These patients might benefit from certain prophylactic interventions, including patient education, prescription footwear, intensive podiatric care, and evaluation for surgical interventions.

Cost-Benefit Analysis↗
PubMed2005

Control of vancomycin-resistant enterococci in the neonatal intensive care unit.

BACKGROUND AND OBJECTIVE: Multidrug-resistant organisms (MDROs), such as vancomycin-resistant enterococci (VRE), cause serious infections, especially among high-risk patients in NICUs. When VRE was introduced and transmitted in our NICU despite recommended infection control practices, we instituted active surveillance cultures to determine their efficacy in detecting and controlling spread of VRE among high-risk infants. METHODS: Active surveillance cultures, other infection control measures, and a mandatory in-service education module on preventing MDRO transmission were implemented. Cultures were performed on NICU admission and then weekly during their stay. Molecular DNA fingerprinting of VRE isolates facilitated targeting efforts to eliminate clonal spread of VRE. Repetitive sequence PCR (rep-PCR)-based DNA fingerprinting was used to compare isolates recovered from patients with VRE infection or colonization. Environmental VRE cultures were performed around VRE-colonized or -infected patients. DNA fingerprints were prepared from the products of rep-PCR amplification and analyzed using software to determine strain genetic relatedness. RESULTS: Active surveillance cultures identified 65 patients with VRE colonization or infection among 1,820 admitted to the NICU. Rep-PCR performed on 60 VRE isolates identified 3 clusters. Cluster 1 included isolates from 21 patients and 4 isolates from the environment of the index patient. Clusters 2 and 3 included isolates from 23 and 3 patients, respectively. Similarity coefficients among the members of each cluster were 95% or greater. CONCLUSIONS: Control of transmission of multi-clonal VRE strains was achieved. Active surveillance cultures, together with implementation of other infection control measures, combined with rep-PCR DNA fingerprinting were instrumental in controlling VRE transmission in our NICU.

Cross Infection↗
PubMed2005

Characterizing vancomycin-resistant enterococci in neonatal intensive care.

Repetitive sequence-based polymerase chain reaction fingerprinting was used to characterize 23 vancomycin-nonsusceptible enterococcal isolates from 2003 to 2004. Five genetically related clusters spanned geographically distinct referring centers. DNA fingerprinting showed infant-to-infant transmission from referring institutions. Thus, community healthcare facilities are a source of vancomycin-nonsusceptible enterococci and should be targeted for increased infection control efforts.

Enterococcus↗
PubMed2004

Rosiglitazone and heart failure: long-term vigilance.

Thiazolidinediones have become a powerful tool for lowering insulin resistance. In many short-term clinical studies, many patients taking thiazolidinediones experience significant improvement in glycemic control and lipid profiles without any adverse effects. Health care providers should be aware that, in long-term follow-up, peripheral edema and congestive heart failure may occur in patients with multiple comorbidities more than 26 weeks after starting thiazolidinediones. This article reports two patients who developed congestive heart failure 6 to 12 months after starting rosiglitazone, in combination with insulin. The patients' glycemic control improved over the first 3 to 6 months of therapy. When edema and congestive heart failure occurred later, they recovered only after medical therapy (diuretics, afterload reduction) was titrated and the rosiglitazone was withdrawn.

Aged↗
PubMed2003

Follow-up of newborns with elevated screening T4 concentrations.

OBJECTIVE: To determine the type and incidence of hyperthyroxinemic disorders detected by follow-up of infants with elevated screening total T4 (TT4) values. STUDY DESIGN: Infants born in Oregon with a screening TT4 measurement >3 SD above the mean were offered enrollment. Serum TT4, free T4, total T3, free T3, and thyroid-stimulating hormone concentrations were measured in study infants and their mothers. RESULTS: Over a 20-month period, 101 infants (51 boys) and their mothers enrolled in the study (of 241 eligible infants), from a total screening population of 80,884; 17 infants were identified with persistent hyperthyroxinemia (TT4 >16 microg/dL). Ten had thyroxine-binding globulin excess (1:8088), 5 had evidence for increased T4 binding but not thyroxine-binding globulin excess (1:16,177), and 2 had findings compatible with thyroid hormone resistance (1:40,442); the other 84 infants had transient hyperthyroxinemia. Sequence analysis revealed a point mutation in the thyroid hormone receptor-beta gene in one infant with thyroid hormone resistance; no mutation was identified in the other infant. CONCLUSIONS: Although neonatal Graves' disease occurs in approximately 1 in 25,000 newborn infants, we did not detect any case among 80,884 infants, most likely because their mothers were receiving antithyroid drugs. Although the other hyperthyroxinemic disorders in the aggregate occur frequently (1:4758) and may benefit from detection, in general they do not require treatment.

Female↗
PubMed2003

Cluster of Trichosporon mucoides in children associated with a faulty bronchoscope.

BACKGROUND: Several outbreaks of Pseudomonas aeruginosa infection associated with a specific model of fiberoptic bronchoscope have been reported. In a 3-week period in September 2000, we noticed an increased number of Trichosporon mucoides isolates recovered from bronchoalveolar lavage (BAL) specimens collected at our hospital. We investigated the circumstances surrounding these isolates. METHODS: Outbreak investigation was conducted, and the medical records of the affected patients were reviewed retrospectively for evidence of positive cultures for T. mucoides from BAL specimens. Specimens collected during the investigation were inoculated onto fungal culture medium and yeasts were identified with API-20C (BioMèrieux-Vitek). RESULTS: During the 3-week period BAL specimens from six patients yielded growth of T. mucoides. These six high risk patients had emergency bronchoscopy performed as a workup for pneumonia and/or respiratory distress. A Model BF XP-40 bronchoscope (Olympus) had been used in all six patients. Cultures of the bronchoscope (external body and the lumen), bronchoscope disinfector, 2% glutaraldehyde disinfecting solution and water filters/supply were performed. Only fluid from the bronchoscope lumen yielded growth of T. mucoides. Air sample cultures of the bronchoscopy suites were negative. Medical records review disclosed that affected patients were not readmitted with infection with T. mucoides and had no adverse outcomes. The bronchoscope was removed from service and returned to the manufacturer. CONCLUSION: Routine surveillance and aggressive investigation identified persistent T. mucoides contamination of one bronchoscope. The bronchoscope manufacturer later recalled the BF XP-40 model for corrective revision.

Adolescent↗
PubMed2003

Outbreak of invasive disease caused by methicillin-resistant Staphylococcus aureus in neonates and prevalence in the neonatal intensive care unit.

OBJECTIVES: To describe an outbreak of severe invasive disease caused by methicillin-resistant Staphylococcus aureus (MRSA) and the epidemiology of MRSA in a neonatal intensive care unit during a 12-yr period from 1989 to 2001. SETTING: A 40-bed, level III neonatal intensive care unit at a children's hospital that admits approximately 450 neonates each year from about 35 neighboring hospitals. PATIENTS: All neonates infected or colonized with MRSA during the outbreak are described. All cases of MRSA infection or colonization in the neonatal intensive care unit from 1989 to 2001 were identified from the database maintained by the hospital epidemiology program. RESULTS: During the outbreak, 12 neonates were infected or colonized with MRSA, 11 of whom had the epidemic strain. Seven of these 11 neonates had invasive disease, including bacteremia, meningitis, or urinary tract infection, and four neonates were colonized with the epidemic strain. This outbreak was difficult to control by routine epidemiologic measures, and additional control measures, including closing the neonatal intensive care unit to new admissions and treating all infants with intranasal mupirocin, were implemented. Since the outbreak, the prevalence of MRSA in the neonatal intensive care unit has remained low. CONCLUSIONS: MRSA outbreaks in neonatal intensive care units can be prolonged. Aggressive infection-control measures are often necessary to terminate these outbreaks. Such efforts are essential because MRSA infections in premature neonates can cause significant morbidity and mortality.

Cross Infection↗
PubMed2002

Change in epidemiology of health care-associated infections in a neonatal intensive care unit.

BACKGROUND: Gram-negative rods (GNR) and species are important causes of health care-associated infections in neonatal intensive care units (NICUs). In prior reports, Gram-positive cocci (GPC) have been identified as the most common pathogens causing nosocomial infections in NICUs. OBJECTIVE: To describe the epidemiology of health care-associated infections in a Level III NICU at a free-standing children's hospital. METHODS: All health care-associated infections in neonates from August 1996 to July 2001 were analyzed. Data were collected prospectively by standard surveillance protocols and nosocomial infection site definitions from the National Nosocomial Infection Surveillance system of the Centers for Disease Control and Prevention. RESULTS: During the 5-year study period, 665 pathogens caused 640 infections in the NICU. GNR were the most common pathogens isolated. Of the 665 pathogens 284 (43%) were GNR, followed by 223 (33.5%) GPC, 106 (16%) fungi and 52 (8%) others. spp. were the most common GNR isolated. Ceftazidime resistance was present in 56 of 81 (69%) isolates. Bloodstream and lower respiratory tract infections were the most common sites of infection. More than one-half of the pathogens (388 of 665) were isolated from neonates weighing < or =1000 g. CONCLUSIONS: There is a change in the epidemiology of health care-associated infections in our NICU with a predominance of GNR. This change can impact choice of antimicrobials for the empiric treatment of health care-associated infections in high risk neonates.

Bacteremia↗
PubMed2002

Risk of resistant infections with Enterobacteriaceae in hospitalized neonates.

OBJECTIVE: To determine the risk factors associated with progression from colonization to infection with health care-associated antimicrobial-nonsusceptible Enterobacteriaceae (ANE) in critically ill neonates. STUDY DESIGN: During a 3-year period (1998 to 2000), surveillance rectal cultures were performed on neonates admitted to our Level III neonatal intensive care unit after a cluster of four cases of ANE infection were identified in 1998. ANE were defined as members of the Enterobacteriaceae family that exhibited nonsusceptibility to ceftazidime or laboratory evidence of extended spectrum beta-lactamase (ESBL) production. RESULTS: A total of 1,710 patients were admitted to the neonatal intensive care unit during the study period. Of the 1,710 patients 300 (18%) were excluded from the risk factor analysis. Of the 1,410 remaining neonates the incidence of health care-associated ANE colonization was 17% (240 of 1,410 patients), and 14% of the colonized patients (34 of 240 patients) developed ANE infections. Of the 206 ANE-colonized patients who did not develop disease, 60 (29%) harbored ESBL-producing isolates. Of the 34 ANE-infected patients, 14 (41%) yielded growth of ESBL-producing isolates. Multiple logistic regression analysis revealed that colonized neonates with very low birth weights (<1,000 g) and those who had received prolonged exposures to antimicrobial agents were at increased risk of ANE infections. CONCLUSIONS: Colonization with ANE places hospitalized neonates at risk for development of systemic infections. Very low birth weight (<1,000 g) and prolonged exposure to antimicrobial agents were the only two independent risk factors associated with ANE infection.

Age Factors↗
PubMed2002

Diabetes, heart rate, and mortality.

A large body of evidence indicates that a persistently high heart rate is associated with a significant risk for higher mortality and sudden death in individuals with a variety cardiovascular disorders, as well as in the general population. Heart rates elevated beyond a certain threshold have been found to be a risk factor for mortality in patients with hypertension, in survivors of myocardial infarction, and in patients with impaired cardiac function. Conversely, a naturally slow heart rate, or one that is slow by virtue of sympathetic blockade induced by pharmacologic agents, may result in longer survival. This is particularly evident in the case of beta-adrenergic blocking drugs, especially in patients after myocardial infarction and in those with acute as well as chronic cardiac failure, a syndrome in which there is a complex neurohormonal disturbance with elevated heart rate. Persistently elevated heart rate is also a feature of diabetes mellitus associated with autonomic neuropathy. Whether this also constitutes an independent risk factor for sudden and augmented mortality is not well defined. In this review, the data on the role of increased heart rate as a risk factor for mortality are examined in the context of other factors that may have therapeutic implications.

Animals↗
PubMed2001

The costs associated with nosocomial bloodstream infections in the pediatric intensive care unit.

OBJECTIVE: To assess the operational and subsidiary costs and length of stay (LOS) attributable to nosocomial bloodstream infections (BSI) in a pediatric intensive care unit (PICU). DESIGN: Matched case-control study. SETTING: Sixteen bed PICU in a 250-bed tertiary-care pediatric hospital. PATIENTS: Cases with BSI were prospectively identified from PICU patients who developed a nosocomial BSI from August 1996 to July 1998. Controls were PICU patients who were matched for age, severity of illness, diagnosis, and admission date who did not develop a nosocomial BSI. RESULTS: A total of 38 cases and 38 controls form the basis for this study. The cases and controls were similar with respect to the matching criteria. In addition, the cases and controls did not differ with respect to demographic characteristics or PICU survival. There was a trend toward increased hospital mortality among cases (23.7% vs. 10.5%, p =.084). Significant differences were encountered in the utilization of PICU therapeutic modalities. Cases were significantly less likely to be managed care plan enrollees (36.8% vs. 60.5%, p =.043). Total operational and subsidiary costs for radiology, pharmacy, and laboratory services were significantly higher for cases than controls ($78,272 vs. $35,005, $3,622 vs. $1,432, $8,635 vs. $4,630, and $8,648 vs. $3,971, respectively; all p <.001). The PICU and hospital LOS were significantly higher for cases than controls (19.3 vs. 4.6 days for PICU and 46.7 vs. 24.4 days for hospital; both p <.001). The operational costs attributable to nosocomial infection were $46,133. Radiology, pharmacy, and laboratory costs attributable to nosocomial infection were $2,364, $4,691, and $5,156, respectively. The PICU and hospital LOS attributable to a nosocomial BSI were 14.6 days and 21.1 days, respectively. The attributable mortality rate was 13.1%. CONCLUSIONS: The costs and LOS associated with nosocomial BSI in patients admitted to the PICU were significantly higher than controls.

Journal Article↗