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M R Nelson

Publications and source records attributed to M R Nelson.

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

Effect of a statewide neonatal resuscitation training program on Apgar scores among high-risk neonates in Illinois.

OBJECTIVE: The national Neonatal Resuscitation Program (NRP), started in 1987, provided training to hospital delivery room personnel to standardize knowledge and skills to reduce neonatal morbidity and mortality and increase successful resuscitation during the first few critical minutes after birth. The Apgar score continues to be used as the best established index of immediate postnatal health. The purpose of this study was to evaluate the impact of the NRP instruction in Illinois hospitals by examining Apgar scores among high-risk infants who are likely to benefit from the NRP. METHODS: A retrospective 3-time period cohort design was used (before the introduction of the NRP, 1985-1988; transition when NRP training occurred, 1989-1990; and after NRP training was completed at least once for some delivery room personnel in each Illinois hospital, 1991-1995). Illinois computerized birth certificate files on a selected group of 636 429 high-risk neonates provided information on Apgar scores and maternal characteristics. The American Academy of Pediatrics provided instructor lists to determine when NRP training started and when it was fully implemented in Illinois. Illinois Department of Public Health provided data to categorize hospitals into levels based on type and intensity of neonatal services (Level I, II, II+, III). High-risk neonates were defined as meeting 1 of the following criteria: maternal age <20 years old or >35 years old, birth weight <2500 g or >4000 g, presence of a maternal medical risk factor, and no prenatal care or prenatal care started after the first trimester. Several exclusion criteria were applied including the following: birth records with missing data, multiple birth or congenital anomaly, and hospital information that indicate no birth deliveries in 1 of the 11 study years or delivery outside of a hospital. One-minute and 5-minute Apgar scores were divided into categories for analysis (0-3, 4-6, 7-10). No change or a decrease in a low (0-6) 1-minute Apgar when compared with the 5-minute Apgar was a primary measure to evaluate effect of NRP resuscitation. Variables examined included the following: race/ethnicity, maternal age, level of education, presence of maternal medical risk factor, trimester started prenatal care, complications of labor and delivery, and a low birth weight. Analysis consisted of chi(2) tests, relative risk calculations, and logistic regression to reveal independent associations with no change in low 1-minute Apgar score or continued low (0-6) 5-minute Apgar. RESULTS: A total of 636 429 high-risk birth records was selected for detailed analyses out of 2 077 533 births in Illinois between 1985 and 1995 for 193 hospitals. The number of active NRP instructors in Illinois changed dramatically during the study period; for example, 1 to 6 between 1987 and 1988 to 1096 to 1242 between 1991 and 1995. The percentage of neonates reported to have low (<7) 1-minute Apgar score decreased in 1991 to 1995 overall and for each of 4 hospital levels. Overall and by hospital level, there was a statistically significant lower proportion of high-risk newborns who showed a decrease or no change in their 5-minute Apgar scores after the NRP instruction. After adjusting for several maternal characteristics, logistic regression analysis revealed that high-risk newborns with a low 1-minute Apgar were more likely to increase their 5-minute Apgar after the NRP instruction in 1991 to 1995. Additional analyses indicated that very low birth weight and low birth weight newborns benefited the most from NRP instruction. CONCLUSION: Although previous research has shown that the NRP instruction improves knowledge and skill among health care personnel in the delivery room, both short-term and long-term, there has been little evidence to demonstrate NRP impact on infant morbidity. Several strategies were used in this study to control for bias and to adjust for secular trends in decreased infant morbidity during the study period. This study demonstrated sufficient support for the hypothesis that a significant improvement occurred among neonates in their Apgar score after the NRP instruction in Illinois. Empirical support is provided for the clinical effectiveness of NRP instruction.

Apgar Score↗
PubMed2000

Changes in acquired immunodeficiency syndrome-related lymphoma since the introduction of highly active antiretroviral therapy.

Clinical data on 7840 HIV-positive patients, representing 43 745 patient-years of follow-up, has been collected. All patients with ARL since 1986 (n = 150) were assessed at presentation for prognostic factors and outcomes recorded. Comparisons are made between cases in the pre-HAART era (1988-1995), and the HAART era (1996-1999). Statistical models are used to calculate the incidence of ARL and factors predicting its development. The incidence of ARL has not changed over time (3 to 7 of 1000 patients per year, P = .933), but contributes to a greater percentage of first AIDS-defining illnesses (ADI) in the HAART era (P < or = .0001). Older age, nadir CD4 count, and no prior HAART use, predict the development of ARL. There has been no change in stage at presentation, presence of B symptoms, performance status, or marrow involvement between the 2 time cohorts or between patients with or without prior HAART exposure. Similarly, there is no difference in survival duration between the pre-HAART and HAART era (log rank P = .15) or specifically in patients treated with HAART before ARL diagnosis (log rank P = .12). The use of HAART has not yet been shown to influence the incidence or survival of ARL. However, because nadir CD4 count and use of HAART are independent predictors of ARL development, this may translate into a future fall in new cases. (Blood. 2000;96:2730-2734)

Adult↗
PubMed1999

Evaluation of sperm washing as a potential method of reducing HIV transmission in HIV-discordant couples wishing to have children.

OBJECTIVE: A number of discordant couples, in whom the man is HIV positive and the woman is HIV negative, wish to have children. To conceive they must abandon protected sex, posing a risk of HIV transmission to the woman and so to the child. In such circumstances purification of spermatozoa ('sperm-washing') to inseminate the woman artificially has been proposed as a method of reducing the risk of transmission. Here we evaluate whether this does represent a true risk reduction. METHODS: Semen samples from HIV-positive patients were separated into spermatozoa, non-sperm cells (NSCs) and plasma fractions. The amount of viral RNA present in each fraction was measured and compared with the level in the peripheral blood. Each fraction was also assessed for the presence of proviral DNA. The ability of spermatozoa to be infected was assessed by evaluating for the presence of HIV receptors, i.e. CD4, CCR5 and CXCR4 on the surface of the sperm, by flow cytometry. RESULTS: A poor correlation was found between the levels of HIV in blood and semen. Within the semen the virus was restricted to the plasma and/or NSCs. All spermatozoa were negative for viral RNA or proviral DNA. Spermatozoa did not express significant levels of CD4, CCR5 or CXCR4, suggesting that they are unlikely to be major targets for HIV infection. CONCLUSIONS: These data suggest that spermatozoa are not major targets of HIV infection. Purifying spermatozoa reduced the level of HIV RNA and proviral DNA to below the detection limit of the assays irrespective of the amount of virus present in the unfractionated semen. On the basis of these data we would recommend 'sperm-washing' followed by insemination as a safer alternative to natural conception for HIV-discordant couples wishing to have children.

DNA, Viral↗
PubMed1999

ICU admission in patients infected with the human immunodeficiency virus - a multicentre survey.

We conducted a retrospective study to assess the reasons for admission to the intensive care unit, and subsequent outcome, in patients infected with the human immunodeficiency virus (HIV). Four hospitals in the south of England participated, all with specialist HIV units. Data were collected on 127 patients admitted to ICU on 133 separate occasions between June 1993 and October 1997. The mean age on admission was 38 years (range 23-60 years). Ninety-four patients (70.7%) were documented HIV-positive before admission and 36 (27%) were diagnosed HIV-positive for the first time during admission; 36.1% were admitted with Pneumocystis carinii pneumonia. Overall ICU mortality was 33%, in-hospital mortality was 56% and the eventual mortality at the end of follow-up (March 1998) was 72%. Survival was highest in those admitted with respiratory HIV-related disease or HIV-unrelated illness. Associations with poor outcome included a prior AIDS-defining illness, a CD4 cell count of less than 100 cells.ml-1 and admission secondary to sepsis.

AIDS-Related Opportunistic Infections↗
PubMed1999

Induction of HIV-1-specific T cell responses by administration of cytokines in late-stage patients receiving highly active anti-retroviral therapy.

Highly active anti-retroviral therapy (HAART) is associated with reduction in the morbidity and mortality of patients with advanced HIV-1 disease. The ability of such treatment to improve immune responses against HIV-1 and opportunistic pathogens is variable and limited. Addition of cytokine immunotherapy to this treatment may improve immune responses. IL-2 with or without granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered to HIV-1+ individuals receiving HAART with undetectable viral loads, and CD4 counts < 100 cells/microl. In one patient presenting with Mycobacterium avium complex (MAC) infection, we evaluated the effect of cytokine immunotherapy on lymphocyte phenotype; plasma viral load; proliferative responses to mitogens, recall and HIV-1 antigens; cytokine production and message in response to non-specific and specific stimuli; and natural killer (NK) cell activity. Proliferation assays were performed in two similar patients. Before cytokine immunotherapy the predominant CD8+ population was mainly CD28-. No proliferation or IL-2 production was seen in response to mitogens, recall or HIV-1 antigens; and no HIV-1 peptide-specific interferon-gamma (IFN-gamma)-secreting cells were present. Low levels of IL-4 were detected in response to antigens to which patients had been exposed, associated with up-regulated expression of costimulatory molecules influenced by IL-4. Following IL-2 administration, loss of IL-4 was associated with increased NK cell activity and HIV-1 peptide-specific and non-specific IFN-gamma-producing cells. Proliferative responses associated with IL-2 production and responsiveness were only seen after subsequent concomitant administration of GM-CSF with IL-2. These changes mirrored clinical improvement. An imbalance of lymphocyte subsets may account for immune unresponsiveness when receiving HAART. Restoration of responses following immunotherapy suggests a shift towards a lymphocyte profile with anti-pathogen activity.

Acquired Immunodeficiency Syndrome↗
PubMed1999

A placebo-controlled phase I/II study of adefovir dipivoxil in patients with chronic hepatitis B virus infection.

Adefovir dipivoxil (bis-POM PMEA) is an adenine nucleotide analogue with activity against retroviruses and herpesviruses, and in vitro activity against hepatitis B virus (HBV). This study was conducted to evaluate its safety and antiviral activity in patients with chronic HBV infection. Twenty patients (13 co-infected with human immunodeficiency virus, HIV) were randomized in a phase I/II, double-blind, placebo-controlled study. Patients who had been hepatitis B surface antigen (HBsAg)/hepatitis B e antigen (HBeAg) positive for > or = 6 months, with elevated hepatic transaminases and serum HBV DNA > or = 50 pg ml-1, were randomized to adefovir dipivoxil 125 mg (n = 15) or placebo (n = 5) as a single, daily, oral dose for 28 days. Antiviral activity was assessed by changes in serum HBV DNA (using the Digene Hybrid Capture assay) and HBeAg/hepatitis B e antibody (HBeAb) status. HBV DNA levels fell rapidly by > 1 log10 in all active drug recipients (median fall 1.8 log10 pg ml-1) but increased by 0.01 log10 pg ml-1 in controls (P = 0.002). Reductions were sustained during treatment. HBV DNA returned to baseline over 1-6 weeks following discontinuation of active drug. HBeAg became transiently undetectable in one patient on treatment and, in another, sustained seroconversion to HBeAb occurred 12 weeks after treatment ended. Liver transaminase elevations > 300 U l-1 were observed in three patients during therapy (leading to protocol-specified treatment discontinuation or dose reduction) and in four patients during follow-up. On-treatment transaminase elevations were associated with HIV status, occurring in three of six HIV-uninfected patients compared with none of nine who were HIV infected. In addition, a slower return to baseline of serum HBV DNA levels was observed in the non-HIV-infected patients. Treatment for chronic hepatitis B as a once-daily oral dose was well tolerated and associated with significant and sustained reductions in serum HBV DNA levels during treatment. Transaminase elevations, which may be related to the therapeutic effect, were observed during and after treatment. Further studies are warranted to investigate the safety, and optimum dose and duration, of adefovir dipivoxil treatment for chronic hepatitis B.

Adenine↗
PubMed1999

Influence of apolipoprotein E genotype variation on the means, variances, and correlations of plasma lipids and apolipoproteins in children.

The impact of the three most common apolipoprotein E (APOE) genotypes (epsilon 32, epsilson 33, and epsilon 43) on means, variances, and correlations of nine plasma lipid and apolipoprotein traits (total cholesterol, InTriglycerides, HDL cholesterol, and apolipoproteins AI, AII, B, CII, CIII, and InE) was studied in 212 unrelated female and 219 unrelated male children aged 5-21.5 years from 278 pedigrees ascertained without regard to health status from Rochester, Minnesota. There was significant heterogeneity (p < or = 0.05) among genotypes for the mean plasma levels of InApo E, Apo CII, Apo CIII, and InTriglycerides (InTrig) in females, and for the means of InApo E, Apo B, and total cholesterol (Total-C) in males. Significant heterogeneity of intragenotypic variance was observed in males for Apo CII, InTrig, and HDL-C; no significant heterogeneity was observed in females. Pairwise correlations between traits differed significantly among APOE genotypes in both females (6 of 36 pairs) and males (5 of 36 pairs). These results differ from those obtained from studies of the parental generation from the same sample of pedigrees. Our study further demonstrates that, with the exception of mean InApo E levels, the univariate and bivariate distributions of traits that are measures of lipoprotein metabolism are influenced by variation in the APOE gene in a gender- and generation-dependent manner.

Adolescent↗
PubMed1999

What's new in HIV.

Explore the source record for details and available documents.

Anti-HIV Agents↗
PubMed1999

Acid-alcohol fast bacilli in sputa of HIV-infected patients.

We identified 34 HIV-infected patients with sputum smear positive for acid-alcohol fast bacilli (AAFB) to determine any factors predictive of subsequent species identification. There were 20 cases of Mycobacterium tuberculosis (MTB), 9 cases of Mycobacterium avium-intracellulare (MAI), 3 cases of Mycobacterium kansasii and one each of Mycobacterium malmoense and Mycobacterium fortuitum. Factors associated with isolation of MAI were lower CD4 cell count, a higher incidence of previous AIDS diagnosis, a history of dyspnoea and a normal chest X-ray. The organism was isolated from blood cultures in 58% of patients with MTB and 78% of patients with MAI infection. Disseminated disease was diagnosed in 45% of MTB patients and 33% of MAI patients.

AIDS-Related Opportunistic Infections↗
PubMed1998

Safety, pharmacokinetics, and antiretroviral activity of the potent, specific human immunodeficiency virus protease inhibitor nelfinavir: results of a phase I/II trial and extended follow-up in patients infected with human immunodeficiency virus.

The safety, antiretroviral activity, and pharmacokinetic profile of nelfinavir, a potent and specific inhibitor of human immunodeficiency virus (HIV) protease, were assessed in a small open-label phase I/II dose-ranging study in protease inhibitor-naive HIV-positive men. A total of 22 patients with baseline plasma HIV RNA > or = 20,000 copies/mL and CD4+ counts between 200 and 500 cells/mm3 were enrolled in the study. Of the 22 patients, 20 were evaluated for activity; 10 patients assigned to 771 mg/day base equivalent (300 mg three times daily) and 10 patients assigned to 1,026 mg/day base equivalent (600 mg twice daily) given monotherapy. A capsule formulation of nelfinavir was used. The initial study period was 28 days; patients showing a virologic response of 1 log10 reduction were eligible for enrollment in an extension phase and addition of nucleoside analogues. A maximally tolerated dose of nelfinavir was not established. A dose-response relationship was observed for four (40%) patients in the 771-mg group and six (60%) patients in the 1,026-mg group experiencing a reduction from baseline in plasma HIV RNA of at lest 1 log during the 28-day study. Of these patients, five sustained the reduction in plasma HIV RNA beyond day 28 (2 patients receiving 771 mg/day and 3 patients receiving 1,026 mg/day). Median increases from baseline in CD4+ counts at day 28 were 216 cell/mm3 and 86 cell/mm3 in the 771-mg and 1,026-mg groups, respectively. After oral administration, median nelfinavir plasma concentrations on day 28 reached a maximum at 1 hour (2,966 ng/mL) in the 771-mg group and at 3 hours (3,157 ng/mL) in the 1,026-mg group. Data for 22 patients were included in the safety analysis; 12 patients (55%) reported at least one grade 2 or worse (moderate, severe, or very severe) adverse event. The most common grade 2 or worse adverse event was diarrhea, reported by two patients (20%) receiving 771 mg/day and seven patients (70%) receiving 1,026 mg/day; followed by nausea, flatulence, asthenia, and headache (each reported in 1 patient [10%] in the 771-mg group) and dizziness (reported in 1 patient [10%] receiving 1,026 mg/day). In the small subgroup (n = 6) who continued taking nelfinavir for longer periods (between 8 and 15 months), virologic responses were sustained in the majority of patients with good tolerability. Nelfinavir is an active HIV-protease inhibitor with favorable pharmacokinetics, good tolerability, and sustained antiviral effects. Results of this early phase I/II dose-ranging study provided data for the safety and antiretroviral activity of nelfinavir and led to the selection of higher doses for phase II/III trials to further optimize virologic and immunologic responses.

Adolescent↗
PubMed1998

An interaction-based analysis of calcium-induced conformational changes in Ca2+ sensor proteins.

Calcium sensor proteins translate transient increases in intracellular calcium levels into metabolic or mechanical responses, by undergoing dramatic conformational changes upon Ca2+ binding. A detailed analysis of the calcium binding-induced conformational changes in the representative calcium sensors calmodulin (CaM) and troponin C was performed to obtain insights into the underlying molecular basis for their response to the binding of calcium. Distance difference matrices, analysis of interresidue contacts, comparisons of interhelical angles, and inspection of structures using molecular graphics were used to make unbiased comparisons of the various structures. The calcium-induced conformational changes in these proteins are dominated by reorganization of the packing of the four helices within each domain. Comparison of the closed and open conformations confirms that calcium binding causes opening within each of the EF-hands. A secondary analysis of the conformation of the C-terminal domain of CaM (CaM-C) clearly shows that CaM-C occupies a closed conformation in the absence of calcium that is distinct from the semi-open conformation observed in the C-terminal EF-hand domains of myosin light chains. These studies provide insight into the structural basis for these changes and into the differential response to calcium binding of various members of the EF-hand calcium-binding protein family. Factors contributing to the stability of the Ca2+-loaded open conformation are discussed, including a new hypothesis that critical hydrophobic interactions stabilize the open conformation in Ca2+ sensors, but are absent in "non-sensor" proteins that remain closed upon Ca2+ binding. A role for methionine residues in stabilizing the open conformation is also proposed.

Amino Acid Sequence↗
PubMed1998

Structures of EF-hand Ca(2+)-binding proteins: diversity in the organization, packing and response to Ca2+ binding.

The growing database of three-dimensional structures of EF-hand calcium-binding proteins is revealing a previously unrecognized variability in the conformations and organizations of EF-hand binding motifs. The structures of twelve different EF-hand proteins for which coordinates are publicly available are discussed and related to their respective biological and biophysical properties. The classical picture of calcium sensors and calcium signal modulators is presented, along with variants on the basic theme and new structural paradigms.

Animals↗
PubMed1998

An outbreak of methicillin-resistant Staphylococcus aureus (MRSA) infection in HIV-seropositive persons.

Staphylococcus aureus is a cause of considerable morbidity and mortality in HIV-seropositive persons. Although methicillin-resistant S. aureus (MRSA) is encountered worldwide and in many areas of medical care, little has been reported on clinical infection with MRSA in patients with HIV. We report on an outbreak of MRSA infection in HIV antibody positive patients, using case reports to describe an outbreak of MRSA infection in HIV-seropositive persons. Six cases of clinical MRSA infection were reported over a 4-week period on patients on an HIV dedicated ward. All cases had previous AIDS diagnoses and low CD4 cell counts (median 8 x 10(6)/l; range 0 to 238). Two cases had infected skin lesions and 2 cases had infected indwelling central venous catheters with septicaemia. Two cases had pneumonia, one with concurrent infection at the entry site of a percutaneous endoscopic gastrostomy (PEG) feeding tube. Isolates of MRSA from the 6 cases were compared by pulsed-field gel electrophoresis of Sma1 chromosomal digests. The resultant banding pattern showed the same strain was responsible for all the infections. A seventh inpatient, the index case, had positive carriage with the same strain of MRSA. To define ongoing MRSA carriage after the outbreak, 29 consecutive ward patients were swabbed for MRSA: all were negative. All patients identified with MRSA infection responded to treatment with intravenous teicoplanin, although carriage was unaltered. Four of the 6 cases died within 7 weeks of diagnosis of MRSA. MRSA can cause severe morbidity in patients with end-stage HIV disease. A small outbreak of MRSA was controlled by simple precautionary measures with no subsequent ongoing transmission of MRSA.

AIDS-Related Opportunistic Infections↗