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Biomedical subjects

M Green

Publications and source records attributed to M Green.

At least 379 records · Page 21Linked to original sources
PubMed1993

Baby friendly care.

In 1991, the United Nations Children's Fund (UNICEF) and the World Health Organization (WHO) launched a global campaign called the Baby-Friendly Hospital Initiative (BFHI). The initiative encourages health professionals to promote, protect and support breastfeeding as the optimal method of infant nutrition and enables families to make an informed choice about infant feeding. Hospitals that serve perinatal families are the focus, because what starts in the hospital carries on into the community. Recognizing the vital role of nurses as patient advocates and health promoters, and their position as the largest group of hospital-based health care workers, WHO and UNICEF are asking nurses to facilitate the implementation of the initiative in their hospitals.

Adult↗
PubMed1993

An evaluation of P0.1 measured in mouth and oesophagus, during carbon dioxide rebreathing in COPD.

The pressure generated 100 ms after the onset of an occluded inspiratory effort (P0.1) is advocated and used as a measure of respiratory centre drive. We have re-examined P0.1, measured simultaneously in the mouth (Pmo0.1) and the oesophagus (Poes0.1), during carbon dioxide rebreathing, in eight patients with severe chronic obstructive pulmonary disease, to see whether either indicates central respiratory drive. Pmo0.1 was identical to Poes0.1 in 4 out of 61, greater than Poes0.1 in 18 out of 61, and less than Poes0.1 in 39 out of 61 measurements (overall Poes0.1-Pmo0.1, median +0.075, range -0.175 to +1.01 kPa). Within a rebreathing run in an individual patient, there was considerable variability in the relationship Pmo0.1/Poes0.1 (0.89 +/- 0.24), coefficient of variation (CoV%) 14.4 +/- 3.7%), in the end-expiratory oesophageal pressure (0.7 +/- 0.54 kPa, CoV% 105 +/- 106%), and in the time delay between the onset of a fall in oesophageal pressure (Poes) from the end-expiratory level to the beginning of inspiration, defined as starting when mouth pressure (Pmo) fell below atmospheric pressure (129 +/- 25 ms, CoV% 22.5 +/- 5.3%). We conclude that the problem of determining the true onset of inspiratory muscle activity from pressure data, and the likelihood that breaths are taken from different lung volumes, make it unlikely that Poes0.1 accurately represents central respiratory drive during rebreathing in chronic obstructive pulmonary disease. Furthermore, Pmo0.1 differed from Poes0.1 during rebreathing, and their relationship was not constant, so that Pmo0.1 is even less likely to be a useful reflection of central nervous system output or respiratory centre drive in such patients.

Esophagus↗
PubMed1993

Child care centers: a community resource for injury prevention.

Child passenger safety, a major public health concern, has been addressed by state laws mandating use of child restraint devices. Usage rates in poor and minority communities are disproportionately low. To determine the influence of the child care center within these communities to improve routine use, an educational clinical trial, based on social learning theory was designed. Two urban child care centers enrolling high-risk 2- through 6-year-old children were monitored for correct child restraint use during a 5-month educational intervention at one center. Key features of intervention programming included weekly, developmentally appropriate presentations by the staff to the children and documented parental awareness of the child care center's policy advisory regarding child restraint use. Results demonstrate statistically significant (p < .01) increases in use at the intervention center. This study finds that child care center policy and programming can be effective in promoting child passenger safety.

Accidents, Traffic↗
PubMed1993

Inspiratory muscle effort during nasal intermittent positive pressure ventilation in patients with chronic obstructive airways disease.

Effective intermittent positive pressure ventilation can be achieved noninvasively using a nasal mask, but patient comfort may be compromised and respiratory effort increased unless the trigger threshold is low and the response time of the ventilator short. The effect of nasal ventilation upon inspiratory muscle effort and the functional characteristics of the trigger of a purpose-built ventilator were evaluated in five patients with chronic obstructive airways disease. A measure of inspiratory muscle effort, the average pressure time integral per minute, decreased by at least 80% in four patients and by 50% in one. Only two patients had significant numbers of triggered breaths (17% and 47% of total) during 1 h of ventilation with settings as used at home. Therefore trigger function was evaluated when the patients were made to trigger the ventilator by slowing the control rate. A high resting end-expiratory intrathoracic pressure decreased the effective trigger sensitivity so that a mean (SD) change in oesophageal pressure of 14.8 cmH2O was required to lower mask pressure by 2.4 (0.3) cmH2O and activate the trigger. Even under these conditions of lowest trigger sensitivity inspiratory muscle effort was not increased compared to spontaneous ventilation.

Carbon Dioxide↗
PubMed1993

Morphine glucuronidation in premature neonates.

The glucuronidation of morphine was investigated in 10 premature neonates (postnatal age < 24 h at initiation of treatment) following 24 h of therapy (2 h loading infusion, followed by a constant rate infusion). Morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) were measured in plasma obtained at 24 h in all babies. Plasma concentrations of M3G and M6G correlated significantly with morphine concentration (P < 0.01 in both cases), and with each other (P < 0.001), suggesting that the capacity for morphine glucuronidation in premature neonates is not saturated at the infusion rates used in this study. M3G/morphine and M6G/morphine plasma concentration ratios were independent of morphine infusion rates (P > 0.05) and morphine plasma concentrations (P > 0.05), providing further evidence of linear kinetics. However, M3G/morphine and M6G/morphine plasma concentration ratios increased significantly with increasing birth weight (P < 0.05 in both cases). This probably reflects increase in liver weight with increasing birth weight. Although morphine glucuronidation is deficient in premature neonates, significant concentrations of the respiratory stimulant M3G are achieved rapidly (20% of morphine plasma concentrations at 2 h). At this time, the respiratory depressant M6G could not be detected.

Birth Weight↗
PubMed1993

Transplantation and the pediatric chest.

The plain chest radiograph is the mainstay in the imaging assessment of the chest in a prospective organ recipient and is invaluable in the initial evaluation of posttransplant complications. Although the presence of focal or diffuse air-space disease on a chest radiograph is often nonspecific, this finding helps direct the choice of other diagnostic methods. Among cross-sectional imaging techniques, computed tomography is used most often to further define anatomy and abnormal findings and to guide needle biopsy or aspiration if necessary. A variety of posttransplant complications are discussed, including common postoperative findings, pulmonary infection, and organ rejection.

Child↗
PubMed1992

Pharmacokinetics of the cardioprotector ADR-529 (ICRF-187) in escalating doses combined with fixed-dose doxorubicin.

BACKGROUND: Although doxorubicin is an anticancer agent with a wide spectrum of activity, therapy with this anthracycline must often be discontinued at a time of benefit to the patient because of the drug's cumulative cardiotoxicity. ICRF-187 (ADR-529, dexrazoxane) is a bisdioxopiperazine compound that protects against cardiac toxicity induced by doxorubicin. PURPOSE: Our objectives in this study were to determine the maximum tolerated dose of ADR-529 (which uses a different vehicle than ICRF-187) when given with a fixed doxorubicin dose and to determine whether ADR-529 alters doxorubicin pharmacokinetics. METHODS: Twenty-five patients were treated with doxorubicin (60 mg/m2) preceded by administration of ADR-529 in escalating dosages (i.e., 60, 300, 600, 750, and 900 mg/m2) to groups of three to nine patients. ADR-529 was administered over a 15-minute period beginning 30 minutes before doxorubicin treatment; the protocol was repeated every 3 weeks. Blood was sampled frequently for drug levels, which were determined by high-pressure liquid chromatography with fluorescence (doxorubicin) and electrochemical detection (ADR-529). RESULTS: Dose-limiting neutropenia occurred in four of six previously treated patients at an ADR-529 dose of 600 mg/m2; the dose ratio of ADR-529 to doxorubicin was 10:1. For three additional patients with better Eastern Cooperative Oncology Group performance status and a maximum of one prior chemotherapy regimen, 600 mg/m2 was tolerated, but grade 3 or 4 neutropenia occurred in four of six patients who received an ADR-529 dose of 900 mg/m2 and in three of four patients at a dose of 750 mg/m2. Doxorubicin's estimated terminal half-life was 39.5 +/- 18.3 (mean +/- SD) hours; the area under the curve for plasma concentration of drug x time (AUC) was 1.74 +/- 0.40 (micrograms/microL) x hour. Total-body clearance was 598 +/- 142 microL/m2 per minute (N = 20), and it did not vary with ADR-529 dose. Estimated distribution and elimination phase half-lives for plasma ADR-529 were 0.46 +/- 0.30 hours and 4.16 +/- 2.94 hours, respectively. Total-body clearance was 111 +/- 87 microL/m2 per minute (N = 18); AUC was linear (r2 = .92), and the clearance rate was constant (r2 = .18) from 60 to 900 mg/m2. CONCLUSIONS: Myelotoxicity was dose limiting for ADR-529 at 600-750 mg/m2 when given with a fixed dose of doxorubicin at 60 mg/m2 (dose ratios of ADR-529 to doxorubicin ranged from 10:1 to 12.5:1). When used in combination, ADR-529 did not perturb doxorubicin's distribution, metabolism, or excretion; therefore, other mechanisms of cardioprotection must be involved. IMPLICATIONS: We recommend that an ADR-529 dose of 600 mg/m2 be given with single-agent doxorubicin at a dose of 60 mg/m2 in future studies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

London after Tomlinson. Clinical research.

Sir Bernard Tomlinson's report focuses on London's health services, but his proposals have major implications for the future of clinical research--not just in London but in the United Kingdom as a whole. They must be seen in the context of a widely perceived decline in British research and development which also threatens clinical research. This article examines the implications of Tomlinson's proposals and related strategies and recommends the construction of a research market for the patient costs of clinical research to complement the NHS market for patient services introduced in 1991. These arrangements would help sustain the clinical research base and guarantee excellence.

Economic Competition↗
PubMed1992

Determination of the sequence of an expressible cDNA clone encoding ERp60/calregulin by the use of a novel nested set method.

An analysis of the N-terminal sequence of the luminal endoplasmic reticulum protein, ERp60, showed that it was identical to the well-characterized Ca2+-binding protein, calregulin. A full-length, expressible cDNA clone encoding this protein was isolated from a mouse fibroblast cDNA library. A novel nested set strategy for the production of overlapping fragments for DNA sequencing was used to determine the complete nucleotide (nt) sequence of both strands of the ERp60 clone. This method utilizes a series of nonspecific deletion primers in conjunction with a specific site primer to generate the nested set fragments. This procedure possesses several advantages over other nested set techniques, since it does not require (i) the re-cloning of the DNA insert into other vectors, (ii) any prior knowledge of the restriction sites of the nt sequence, or (iii) the transformation and analysis of bacterial subclones. ERp60 has a 17-amino acid (aa) signal sequence and the mature protein contains 399 aa with a calculated M(r) of 46,347.

Amino Acid Sequence↗
PubMed1992

HLA-DR associates with specific stress proteins and is retained in the endoplasmic reticulum in invariant chain negative cells.

The major histocompatibility complex class II molecules are composed of two polymorphic chains which, in cells normally expressing them, transiently associate with a third, nonpolymorphic molecule, the invariant chain (Ii). To determine differences in the biology of class II molecules synthesized in the presence or absence of Ii, a comparative study was performed of BALB/c 3T3 cells that had been transfected with human class II HLA-DR molecules with or without cotransfection with human Ii. It was observed that in the absence of Ii, at least three high molecular weight proteins coimmunoprecipitate with HLA-DR molecules. These proteins did not coimmunoprecipitate with HLA-DR from cells cotransfected with Ii, nor did they coimmunoprecipitate with class I molecules from any of the transfectants. NH2-terminal sequence and/or Western blot analysis revealed the identity of two of the proteins as the endoplasmic reticulum (ER) resident stress proteins GRP94 and ERp72. Neither of these proteins was found to have an increased level of synthesis in the Ii- versus the Ii+ transfectants, indicating that their synthesis was not induced over constitutive levels. Fluorescence microscopy revealed that in the Ii- transfectants, the majority of the HLA-DR molecules were present in the ER, whereas in the Ii+ transfectants, the HLA-DR molecules were found in vesicular structures. We hypothesize that in the absence of Ii, ER resident stress proteins bind to class II molecules and retain them in the ER. This process, in turn, could prevent class II molecules from exiting the ER with endogenous peptides bound in their peptide binding cleft, and therefore could minimize autoimmune responses to endogenously processed self-peptides.

3T3 Cells↗
PubMed1992

Comparison of different metronidazole therapeutic regimens for bacterial vaginosis. A meta-analysis.

OBJECTIVE: To evaluate the treatment of bacterial vaginosis with metronidazole to determine if there is a therapeutic regimen that is superior to all others with regard to cure and recurrence rates. DATA SOURCES: Computer-assisted literature search, Medical Subject Index review, and references cited in articles identified. STUDY SELECTION: Clinical trials comparing different oral metronidazole regimens in which diagnostic criteria for bacterial vaginosis and criteria to detect cure to treatment were described. DATA EXTRACTION: Articles that met inclusion criteria were critically appraised and those that passed were included in the analysis. Of 52 initial articles, 10 met criteria for inclusion and passed critical appraisal. DATA SYNTHESIS: Patients were divided in groups according to the duration of therapy received: group A (n = 413), 2-g single dose; group B (n = 193), 2-g single daily dose for 2 days; group C (n = 317), 5 days; and group D (n = 280), 7 days. Cure rates on initial evaluation for the groups were 85%, 87%, 86%, and 87%, respectively. chi 2 Contingency table analysis showed no significant difference in cure rates among the groups (P = .78). Only 465 of these patients were evaluated for recurrence of disease. There was no significant difference in cure rates after 4 weeks of therapy (P = .4). CONCLUSIONS: A 2-g single-dose metronidazole regimen is as effective as a single daily dose given for 2 days or a 5-day course or a 7-day course.

Female↗
PubMed1992

Rapid optimization of enzyme substrates using defined substrate mixtures.

A strategy is described for the rapid optimization of kcat/Km for protease substrates. Selected positions of a given peptide substrate sequence are varied through synthesis with mixtures of amino acids. Incubation of the resulting peptide mixture with the enzyme of interest and analysis by high pressure liquid chromatography provides a direct measure of analogs with enhanced kcat/Km. High performance liquid chromatography/continuous flow fast atom bombardment mass spectrometry is used to assign structure to each peak in the chromatogram. As an example of the utility and efficiency of "substrate mapping" we describe optimization of the collagenase substrate Dnp-Pro-Leu-Gly-Leu-Trp-Ala-D-Arg-NH2 (where Dnp is dinitrophenyl) at the P'1 and P'2 positions. Six different mixtures were prepared for evaluation, representing the synthesis of 128 different synthetic substrates. "Substrate mapping" has led to Dnp-Pro-Leu-Gly-Cys(Me)-His-Ala-D-Arg-NH2, a substrate that possesses a 10-fold better kcat/Km than Dnp-Pro-Leu-Gly-Leu-Trp-Ala-D-Arg-NH2.

Amino Acid Sequence↗
PubMed1992

Ventricular performance before and after Fontan repair for univentricular atrioventricular connection: angiographic and radionuclide assessment.

OBJECTIVES: This study was designed to evaluate changes in ventricular volume, mass and cardiac function before and after creation of an atrial to pulmonary connection in patients with a univentricular atrioventricular connection. BACKGROUND: Intact systolic and diastolic performance is critical for successful establishment of an atrial dependent circulation, and few studies are available comparing cardiac performance before and after creation. METHODS: With the use of radionuclide blood pool imaging and ventricular cineangiography, 54 patients (mean age 6.4 +/- 3.4 years) were studied. Twenty-eight patients were investigated preoperatively and 36 greater than 1 year after repair and compared with a control population. RESULTS: Before operation, end-diastolic volume and wall mass were significantly increased compared with those of control subjects; however, the mass/volume ratio was normal (1.08 +/- 0.31 g/ml for the preoperative group; 0.97 +/- 0.19 for control subjects). Although end-diastolic volume returned to normal after the procedure, wall mass remained elevated and contributed to an elevated mass/volume ratio (1.20 +/- 0.38 g/ml). After the procedure, systemic vascular resistance index was significantly elevated compared with that before surgery or with that of control subjects (1,199 +/- 373, 2,120 +/- 645, 1,556 +/- 275 dynes.s.cm-5.m2: pre- and postrepair and control subjects, respectively). Radionuclide studies demonstrated that preoperative ejection fraction (52 +/- 9, 50 +/- 9, 60 +/- 8%), peak ejection (2.58 +/- 0.66, 2.95 +/- 0.81, 3.73 +/- 0.70 EDV/s) and peak filling rates (2.84 +/- 0.75, 2.75 +/- 0.79, 3.84 +/- 0.51 end-diastolic volumes [EDV/s]) were significantly reduced compared with those of control subjects and remained so after surgery. CONCLUSIONS: These data suggest that systolic and diastolic function is depressed preoperatively in these patients, remains unchanged after the creation of an atrial-dependent circulation and is associated with an increased systemic vascular resistance. Long-term issues addressing preservation of cardiac function need to be prospectively studied.

Child↗
PubMed1992

Visual search: detection, identification, and localization.

In two studies, observers searched for a single oblique target in a field of vertical distractors. In one experiment, target detection and identification (left versus right tilt) were compared. In another experiment, detection and localization were compared for the left versus the right half of the display. Performance on all three tasks was virtually identical: if a target could be detected, it could also be identified and localized. A review of previous studies generally supports the conclusion that performance on the three tasks is similar. This argues against current search theories, which rest heavily on data showing differences in identification and localization.

Attention↗
PubMed1992

The expression of murine protein disulfide isomerase in Escherichia coli.

Protein disulfide isomerase (PDI), a luminal enzyme of the endoplasmic reticulum (ER), is thought to be involved in the process that assures that the correct disulfide bonds form as a newly synthesized protein folds into its appropriate three-dimensional structure (Freeman, 1984). In recent years, the ER has been shown to have at least two additional, distinct PDI-related luminal proteins (Bennett et al., 1988; Mazzarella et al., 1990). As a potential first step toward an investigation of the structure and function of PDI and of the PDI-related proteins as well, we have developed a bacterial expression system in Escherichia coli capable of synthesizing significant levels of enzymatically active PDI under the control of the inducible tac promoter. We have observed that the use of this bacterial expression system is complicated by the fact that there is a significant amount of internal initiation of protein synthesis within the PDI coding sequence and the fact that all of the PDI-related expression products are found equally distributed between the cytoplasmic and periplasmic fractions due to a single peptide-independent mechanism. Our studies with this system have demonstrated that at least some truncated PDI molecules containing the carboxy-terminal most active site have significant PDI activity.

Amino Acid Sequence↗
PubMed1992

Respiratory syncytial virus infections in pediatric liver transplant recipients.

Respiratory syncytial virus (RSV) is the most important cause of lower respiratory tract infection in infants and young children. The charts of 17 children found to have RSV among 493 children who underwent liver transplantation between February 1985 and February 1991 were reviewed. The median age at diagnosis was 20 months. Median time of diagnosis was 24 days after transplantation. Thirteen patients developed nosocomial infections while convalescing from their transplant. Common symptoms included tachypnea, cough, fever, and congestion. Acute radiographic changes were seen in 12 patients. Two deaths were associated with progressive pulmonary disease and occurred in children with infection early in the postoperative period who were intubated before the onset of symptoms. RSV in children after liver transplantation has a clinical spectrum similar to that in normal children. Early onset of infection (less than 20 days) after transplantation and preexisting lung disease may predict more severe disease.

Child↗