Search PubMed⌕ Search

Biomedical subjects

S Greene

Publications and source records attributed to S Greene.

At least 37 records · Page 2Linked to original sources
PubMed1998

Comparison of the Maxair Autohaler to wet nebulizer in patients with acute asthma.

STUDY OBJECTIVE: Patients with acute asthma often have difficulty using a conventional metered-dose inhaler. The Maxair Autohaler (3M Pharmaceuticals; St. Paul, MN) is a hand-held breath-actuated device developed to help patients coordinate drug administration. The study objective is to compare the efficacy of the Autohaler with inhaled beta-agonist administered by wet nebulizer in treating acute asthma exacerbations. DESIGN: Parallel, randomized, placebo-controlled clinical trial. SETTING: Emergency department (ED) of a university-affiliated hospital. PARTICIPANTS: Patients aged 18 to 55 years presenting to the ED with acute asthma and an FEV1 40 to 70% on hospital arrival. INTERVENTIONS AND MEASUREMENTS: Patients were given either six puffs of the Maxair Autohaler (1,200 microg pirbuterol) plus saline solution by nebulizer (active Autohaler group) or six puffs placebo by Autohaler plus 2,500 microg albuterol via nebulizer (active nebulizer group). Treatment was repeated at 30 and 60 min, with clinical evaluation performed before each treatment and again at 120 min. At 120 min, the protocol was completed. RESULTS: Twenty-four patients were enrolled, with 5 excluded because of protocol violations. Baseline FEV1 percent predicted values for the active Autohaler group were 53% vs 51% for the active nebulizer group (p=not significant [NS]). At time 120 min, values were 66% for Autohaler and 64% for nebulizer (p=NS). The average time to administer Autohaler was 2.9 min, vs 9.1 min for nebulizer. No patient was excluded because of the inability to use the Autohaler device adequately. CONCLUSION: In patients with moderate asthma exacerbations, similar improvements in pulmonary function are obtained when beta-agonists are given by either the Maxair Autohaler or a wet nebulizer device.

Acute Disease↗
PubMed1997

Prolactin, epidermal growth factor or transforming growth factor-alpha activate a mammary cell-specific enhancer in mouse mammary tumor virus-long terminal repeat.

Mammary specific expression of elevated levels of mouse mammary tumor virus (MMTV) contributes to mammary carcinogenesis. Mechanisms which regulate provirus expression have not been completely defined. Using a MMTV-long repeat terminal (MMTV-LRT) directed chloramphenicol-acetyltransferase (CAT) reporter gene system and a human breast cancer cell line T47D, we demonstrate that prolactin (PRL), epidermal growth factor (EGF), or transforming growth factor-alpha (TGF-alpha) act on a mammary cell-specific enhancer at the extreme 5' end of the MMTV-LTR involving sequences -1094 through -858. PRL and either EGF or TGF-alpha exert concerted roles in this activation of these sequences. In contrast, using a plasmid construct lacking this mammary cell-specific enhancer, EGF or TGF-alpha, but not PRL, act synergistically with progesterone to induce CAT activity, indicating that the action of PRL on regulatory elements of the MMTV-LTR is restricted to this mammary cell-specific enhancer involving sequences -1094 through -858. A mobility shift assay was used to demonstrate that PRL, EGF or TGF-alpha induce nuclear factors (MP4, MAF, and MGF) which bind directly to this mammary cell-specific enhancer element.

Binding Sites↗
PubMed1996

A new therapeutic option for the treatment of pneumonia.

Patients with bacterial pneumonia often are treated empirically with parenteral broad-spectrum antimicrobials intended to cover potential gram-negative and gram-positive pathogens. However, beta-lactamase-mediated resistance has developed to many of these antimicrobials, particularly third-generation cephalosporins, and has led to the development of fourth-generation agents that are relatively beta-lactamase stable. The purpose of these studies was to compare the efficacy and safety of the fourth-generation agent, cefepime, with that of the third-generation agent, ceftazidime, in the treatment of hospitalized patients with moderate-to-severe bacterial pneumonia. A total of 336 (97 evaluable) patients were enrolled in an open-label study, and 99 (23 evaluable) patients were enrolled in a blinded study of patients with lower respiratory tract infections (LRTI) including pneumonia. Patients were randomized to receive either cefepime 1 g every 12 hours or ceftazidime 1 g every 8 hours given as an intravenous infusion over 30 minutes. Efficacy analysis included the evaluable patients while the safety analysis included all patients. The results in the open-label study were as follows: In patients with pneumonia, clinical response was satisfactory in 58 (85%) of 68 patients in the cefepime group and 21 (72%) of 29 patients in the ceftazidime group. Bacteriologic eradication occurred for 75 (93%) of 81 pathogens and 30 (94%) of 32 pathogens isolated from the 68 cefepime-treated patients and 29 ceftazidime-treated patients, respectively. The results in the blinded study were as follows: In patients with pneumonia, clinical response was satisfactory in 12 (80%) of 15 cefepime patients and in 7 (88%) of 8 ceftazidime patients, and the bacteriologic eradication rates were 85% (17/20 pathogens) and 73% (8/11 pathogens) isolated from the 15 cefepime-treated patients and the eight ceftazidime-treated patients, respectively. Among the most frequent adverse events in both groups were nausea, diarrhea, vomiting, and abdominal pain. Similar adverse events were noted in the 99 patients in the blinded study. These studies indicate that the efficacy and safety of cefepime administered at 1 g twice daily is comparable to that of ceftazidime administered at 1 g three times daily for treatment of hospitalized patients with pneumonia caused by susceptible pathogens.

Acute Disease↗
PubMed1995

Inhibition of dihydroorotate dehydrogenase by the immunosuppressive agent leflunomide.

Leflunomide [HWA 486 or RS-34821, 5-methyl-N-(4-trifluoromethylphenyl)-4-isoxazole carboximide] is an immunosuppressive agent effective in the treatment of rheumatoid arthritis. In spite of its clinical potential, its mechanism of action has not been elucidated. Recent studies suggest that leflunomide may interfere with the metabolism of pyrimidine nucleotides. In our studies, the active metabolite of leflunomide, RS-61980 (A77 1726, 2-hydroxyethylidene-cyanoacetic acid-4-trifluoromethyl anilide), was cytostatic towards a human T-lymphoblastoma cell line (A3.01). The inhibition of growth could be overcome completely by uridine. The other nucleosides, cytidine, adenosine and guanosine, did not overcome the effect of the compound. Since uridine is a precursor for the salvage synthesis of UMP, we propose that RS-61980 may be inhibiting the de novo pathway of UMP synthesis. Using human cells, the six enzymes catalyzing de novo UMP biosynthesis were tested for their sensitivity towards RS-61980. Only one of the enzymes, dihydroortate dehydrogenase (DHODH, EC 1.3.3.1) was inhibited by RS-61980 with a Ki value of 2.7 +/- 0.7 microM. The other five enzymes were not affected. The inhibition exhibited mixed-type kinetics towards both substrates, dihydroorotic acid and coenzyme Q. These results suggest that the molecular target of leflunomide action is DHODH. The immunomodulating activity may be related to the inhibition of UMP synthesis in proliferating lymphocytes.

Aniline Compounds↗
PubMed1995

Predictive value of precore hepatitis B virus mutations in spontaneous and interferon-induced hepatitis B e antigen clearance.

We previously reported two mutually exclusive mutations in the precore region of hepatitis B virus: M1 (T-1856, proline-serine substitution at codon 15) and M2 (A-1896, stop codon at codon 28). This study was conducted to determine if the presence of precore mutants affect spontaneous or interferon (IFN)-induced hepatitis B e antigen (HBeAg) clearance. Sera from 201 hepatitis B e antigen positive Chinese patients (including 106 who participated in a controlled trial of IFN therapy) with chronic hepatitis B virus (HBV) infection were analyzed by direct sequencing of HBV DNA after amplification by polymerase chain reaction (PCR) assay. Forty-three (21%) patients had M1 (T-1856), and 20 patients (10%) had M2 (A-1896). During a follow-up period of 1 to 7 years, 75%, 28%, and 26% of those with M2 (A-1896), M1 (T-1856), and wild type sequence respectively, cleared HBeAg (P < .0001). Eighteen (67%) of 27 patients with wild-type sequence but none of 10 patients who had M1 (T-1856) in their initial samples developed M2 (A-1896) after loss of HBeAg (P < .0001). Sustained antiviral response was achieved in 55%, 0%, and 17% of interferon-treated patients who had M2 (A-1896), M1 (T-1856), and wild-type sequence, respectively, initially (P = .04). However, patients with M2 (A-1896) were also more likely to have elevated pretreatment aminotransferase levels (P = .02). In summary, HBeAg-positive Chinese patients with M2 (A-1896) were mor likely to clear HBeAg, and to do so earlier.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1994

Mutations in the pre-core region of hepatitis B virus serve to enhance the stability of the secondary structure of the pre-genome encapsidation signal.

We conducted a large-scale survey to determine the frequency and clinical significance of mutations in the pre-core region of hepatitis B virus (HBV). Sera from 263 patients with chronic HBV infection were analyzed by direct sequencing of PCR-amplified HBV DNA. Four major missense/nonsense mutations (M) were found: (M1) C-->T at nucleotide position 1856, Pro-->Ser at codon 15; (M2) G-->A at position 1896, Trp-->stop at codon 28; (M3) G-->A at position 1898, Gly-->Ser at codon 29; and (M4) G-->A at position 1899, Gly-->Asp at codon 29. The commonest conserved mutation was M0: T-->C at position 1858, Pro-->Pro at codon 15. We found that M1 and M2 were mutually exclusive, M3 was only found in association with M1, and M4 was predominantly found in association with M2. All patients with M1 but none of those with M2 had M0. The invariable coexistence of certain mutations in codon 15 and codons 28 and 29 and the mutual exclusion of other mutations in these two noncontiguous regions is related to the stem-loop structure of the pre-genome encapsidation sequence located in the precore/core region. M2 and M4 enhance the stability of the stem by providing two additional paired sites. M1 destroys an existing base pair. However, M1 only occurred in the presence of M0, which provides an extra paired site, and 50% of patients with M1 had M3, a compensatory mutation that restores base pairing at this site. Our data support the proposed secondary structure of the pre-genome encapsidation sequence. The primary function of the mutations in the pre-core region is to enhance stability of this secondary structure to ensure perpetuation of viral replication.

Base Sequence↗
PubMed1994

Use of glycated hemoglobin to assess Glycemic control in Wistar diabetic fatty rats and Zucker fatty rats.

The Wistar Diabetic Fatty rat (WDF fafa) is a congenic strain of the Wistar Kyoto rat. Studies using blood glucose reveal that only fatty male (not female) WDF rats spontaneously develop hyperglycemia when fed a stock diet. Blood glucose values have not provided consistent results for evaluation of glycemic status in fatty male WDF rats. Zucker fatty (fafa) rats, while sharing the fa gene and the development of hyperinsulinemia and hyperlipemia, do not spontaneously become hyperglycemic. In order to examine strain differences and the effects of age on long-term average glycemic status in WDF and Zucker rats, glycated hemoglobin (GHb) was analyzed. Glycated hemoglobin was measured in male lean and obese WDF and Zucker rats at 2, 3, 6, and 12 months of age. Nonfasted plasma glucose was measured in male lean and obese WDF rats at 2, 3, 6, and 12 months of age and in lean and obese Zucker rats at 3, 6, and 12 months of age. Plasma insulin was measured in lean and obese WDF and Zucker rats at 3, 6, and 12 months of age. Obese WDF rats had significantly elevated GHb compared to lean controls at 3, 6, and 12 months of age. Glycated hemoglobin was substantially above the normal range (3.8-6.5%) at 3 months of age (14.1%). Glycated hemoglobin significantly declined in the obese WDF rats between 6 and 12 months of age. Nonfasted plasma glucose was significantly elevated in the obese WDF rats at 3 months (14.1 +/- 2.1 mM/L) and 6 months of age (16.2 +/- 2.3 mM/L) compared to lean controls. At 12 months of age there was no difference in plasma glucose between obese and lean WDF rats. Obese and lean Zucker rats had similar levels of GHb and plasma glucose at all ages. In conclusion, GHb provides more integrated data for classifying disease status of WDF rats and evaluation of potential long-term complications associated with hyperglycemia.

Age Factors↗
PubMed1994

Detection of precore hepatitis B virus mutants in asymptomatic HBsAg-positive family members.

Precore hepatitis B virus mutants have been detected mainly in HBeAg-negative patients with active liver disease. We previously reported two novel mutations: M1 (C-to-T change at nucleotide 1856 [proser at codon 15]) and M3 (G-to-A change at nucleotide 1898 [gly-ser at codon 29]) in addition to two well-described mutations: M2 (G-to-A change at nucleotide 1896 [trp-stop at codon 28]); and M4 (G-to-A change at nucleotide 1899 [gly-asp at codon 29]) in Chinese patients. The aims of this study were to determine (a) the prevalence of precore HBV mutations in asymptomatic carriers and (b) whether family members share the same mutated sequence as the index patients. Fifty-three index patients and 89 HBsAg-positive family members were studied by means of direct sequencing of polymerase chain reaction-amplified hepatitis B virus DNA. M0, a conserved mutation (T-to-C at nucleotide 1858, codon 15), was detected in 81% and 12% family members of index patients with and without M0, respectively (p < 0.0001). The clustering of M0 indicates that most subjects were infected through intrafamilial transmission. M1 was detected in all the family members of patients with M1 but in none of the family members of patients with wild-type or M2 sequences (p < 0.0001). M2 was detected in 25%, 0% and 15% of family members of patients with M2, M1 and WT sequences, respectively (p = 0.19). M3 was detected in five and M4 in four family members.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

NIH appointment due.

Explore the source record for details and available documents.

Administrative Personnel↗