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Biomedical subjects

J Freeman

Publications and source records attributed to J Freeman.

At least 163 records · Page 9Linked to original sources
PubMed1991

Sequence selective binding to the DNA major groove: tris(1,10-phenanthroline) metal complexes binding to poly(dG-dC) and poly(dA-dT).

Molecular modelling and energy minimisation calculations that incorporate solvent effects have been used to investigate the complexation of delta and lambda-[Ru(1,10-phenanthroline]2+ to DNA. The most stable binding geometry for both enantiomers is one in which a phenanthroline chelate is positioned in the major groove. The chelate is partially inserted between neighbouring base pairs, but is not intercalated. For delta, though not for lambda, a geometry with two chelates in the major groove is only slightly less favourable. Minor groove binding is shown to be no more favourable than external electrostatic binding. The optimised geometries of the DNA/[Ru(1,10-phenanthroline]2+ complexes enable published linear dichroism spectra to be used to determine the percentage of each enantiomer in the two most favourable major groove sites. For delta 57 +/- 15% and for lambda 82 +/- 7% of bound molecules are in the partially inserted site.

Base Sequence↗
PubMed1991

A comparison of the results following oromandibular reconstruction using a radial forearm flap with either radial bone or a reconstruction plate.

Fifteen cases of oromandibular reconstruction using a radial osteocutaneous flap were compared with 16 in which the mandible was replaced with a reconstruction plate and a forearm flap was used for intraoral lining. All cases involved oral cancer; most had been irradiated. Nine survived in each group. Complications included one infected nonunion in addition to two bone exposures in the bone group, compared with three cases of plate exposure and two bone exposures in the plate group. Functional results were similar in both, but osteointegrated implants were possible only in the patients receiving bone. Cosmesis seemed somewhat better in the plate group. Donor-site problems were common but minor, and long-term forearm function was slightly reduced in both groups. Although the sample sizes were small, the reconstruction plate together with a radial forearm flap appeared to provide effective reconstruction following composite resection. However, we would not recommend this for the younger patient or in benign disease.

Adult↗
PubMed1991

Therapy of refractory/relapsed acute leukemia with cytosine arabinoside plus tetrahydrouridine (an inhibitor of cytidine deaminase)--a pilot study.

Thirty two patients with refractory or recurrent acute leukemia or blast crisis of chronic myelocytic leukemia were treated with 1-beta-D-arabinofuranosylcytosine (Ara-C), 100 mg/m2 [group I (n = 15)] or 200 mg/m2 [group II (n = 18)], and tetrahydrouridine (THU) 350 mg/m2, given concurrently as a 3 h continuous intravenous infusion at 12 h interval for eight doses. Two of 13 (15.3%) evaluable patients in group I achieved a complete response, both of whom had acute myelocytic leukemia. In group II, seven of 14 evaluable patients (50%) obtained objective responses--six with complete responses (42.8%) and one with partial response (7%). Myelosuppression was seen in all patients with a median duration of 32.5 days (group I) and 36.3 days (group II), respectively. Non-hematologic toxicity consisted of nausea, vomiting, diarrhea, conjunctivitis, skin rash, hepatocellular toxicity, hemorrhage, and renal toxicity. Pharmacokinetic studies revealed, for group I, mean peak plasma Ara-C levels at 3 h (Cp3h) of 1254 ng/ml, area under the curve (AUC) 4651 ng x h/ml, total body clearance (TBC) 32.65 l/h/m2, renal clearance (RC) 7.04 l/h/m2 with a mean of 12.36% of the injected amount of Ara-C excreted unchanged in urine over the first 24 h. The corresponding mean values for group II are Cp3h 3305 ng/ml, AUC 15080 ng x h/ml, TBC 20.48 l/h/m2, RC 7.02 l/h/m2 and 26.23%. Ara-C 200 mg/m2 combined with THU gave serum Ara-C levels and response rates comparable to those achieved with high dose Ara-C (HiDAC) (greater than or equal to 1 g/m2). Central nervous system toxicity associated with HiDAC was not seen. Pharmacokinetics for uracil arabinoside (Ara-U) in patients treated with Ara-C 200 mg/m2 plus THU, were comparable to values seen with Ara-C for Cp3h, AUC and 24 h urine, amounting to 3160 ng/ml, 21717 ng x h/ml and 23.62% whereas TBC was significantly lower (p less than 0.001) for Ara-U than for Ara-C (3.02 versus 20.48 l/h/m2).

Adult↗
PubMed1990

Association of intravenous lipid emulsion and coagulase-negative staphylococcal bacteremia in neonatal intensive care units.

BACKGROUND AND METHODS: Coagulase-negative staphylococci are now the chief cause of bacteremia in neonatal intensive care units. To investigate potential risk factors for this nosocomial infection, we conducted a case--control study among 882 infants treated in two neonatal intensive care units during 1982. RESULTS: The 38 case patients and 76 controls were similar with respect to 27 indicators of the severity of the underlying illness. In addition, of the 20 potential risk factors for bacteremia that we investigated, only 2 met conventional criteria for causality. Infants with coagulase-negative staphylococcal bacteremia were 5.8 times as likely as controls (95 percent confidence interval, 4.1 to 8.3) to have received intravenous lipid emulsion before the onset of bacteremia. Because the use of lipids was common, 56.6 percent of all of the cases of nosocomial bacteremia could be attributed to lipid administration. Infants with bacteremia were also 3.5 times as likely as controls (95 percent confidence interval, 1.4 to 8.3) to have had a percutaneously inserted central venous catheter (attributable risk, 14.9 percent). The induction time for bacteremia after lipid administration, usually through peripheral catheters, was often less than one day. In contrast, the average induction period for nosocomial bacteremia associated with the use of central catheters, which were rarely used for lipid administration, was at least 5.5 days. Similar analyses of data on an additional 31 neonates treated in 1988 confirmed the strong and apparently independent association of coagulase-negative staphylococcal bacteremia with the intravenous administration of lipids (adjusted odds ratio, 5.3; 95 percent confidence interval, 3.5 to 6.7). CONCLUSIONS: The risk of coagulase-negative staphylococcal bacteremia in infants in neonatal intensive care units can be attributed primarily to the intravenous administration of lipid emulsions. Since lipids are critical for the nutritional support of premature infants, further studies are needed to examine the pathogenesis and prevention of lipid-associated bacteremia.

Catheterization, Central Venous↗
PubMed1990

Extra hospital stay and antibiotic usage with nosocomial coagulase-negative staphylococcal bacteremia in two neonatal intensive care unit populations.

Coagulase-negative staphylococci were the leading cause of nosocomial bacteremia in the neonatal intensive care units of the Brigham and Women's Hospital and Children's Hospital, Boston, Mass, in 1982. To determine the consequences of these nosocomial bacteremias, a cohort study was conducted in which two comparison subjects were matched with each of 38 bacteremic infants by hospital, birth weight within 100 g, and nearest date of discharge. To adjust for duration of stay in the hospital, it was also required that both comparison subjects have survived and remained in the hospital for as long as the time until bacteremia occurred in the bacteremic infant. The average day of onset of bacteremia was the 20th hospital day. Despite having similar birth weights and comparable severity of underlying illness, bacteremic infants remained in the hospital for an average of 19.8 days longer than the nonbacteremic comparison subjects (77.3 vs 57.5 days). The bacteremic patients received antibiotics for an average of 11.2 more days than the nonbacteremic infants. Vancomycin hydrochloride was given to 20 (52.6%) of the bacteremic patients but only 4 (5.3%) of the comparison patients. All of the comparison subjects and 37 of the 38 infants with bacteremia survived. Thus, nosocomial bacteremia with coagulase-negative staphylococci is a late complication of hospitalization that occurs in infants who are already relatively long-term survivors. This bacteremia appears to be associated with substantially longer hospital stay and antibiotic therapy but little, if any, excess mortality.

Cross Infection↗
PubMed1990

Molecular analysis of barley mutants deficient in chloroplast glutamine synthetase.

A barley leaf cDNA library has been screened with two oligonucleotide probes designed to hybridize to conserved sequences in glutamine synthetase (GS) genes from higher plants. Two GS cDNA clones were identified as hybridizing strongly to one or both probes. The larger clone (pcHvGS6) contained a 1.6 kb insert which was shown by primer extension analysis to be an almost full-length cDNA. Both clones were more closely related to cDNAs for the chloroplast form of GS (GS2) from pea and Phaseolus vulgaris than to cDNAs for the cytosolic form (GS1). A sequence identical to an N-terminal sequence determined from a purified preparation of the mature GS2 polypeptide (NH2-XLGPETTGVIQRMQQ) was found in the pcHvGS6-encoded polypeptide at residues 46-61, indicating a pre-sequence of at least 45 amino acids. The pre-sequence has only limited sequence homology to the pre-sequences of pea and P. vulgaris GS2 subunits, but is similarly rich in basic residues and possesses some of the structural features common to the targeting sequences of other chloroplast proteins. The molecular lesions responsible for the GS2-deficient phenotypes of eight photorespiratory mutants of barley were investigated using a gene-specific probe from pcHvGS6 to assay for GS2 mRNA, and an anti-GS antiserum to assay for GS2 protein. Three classes of mutants were identified: class I, in which absence of cross-reacting material was correlated with low or undetectable levels of GS2 mRNA; class II, which had normal or increased levels of GS2 mRNA but very little GS2 protein; and class III, which had significant amounts of GS2 protein but little or no GS2 activity.

Amino Acid Sequence↗
PubMed1990

Clinical pharmacokinetics of intravenously injected tritiated vinzolidine.

Vinzolidine (VZL), a novel, semi-synthetic vinca alkaloid showing evidence of oncolytic activity in phase I/II clinical trials, was studied in six patients for its pharmacokinetic and metabolic behavior. Following i.v. administration of [3H]-VZL at doses of 5, 6.7, and 9 mg/m2, blood and urine samples were collected and analyzed by sample oxidation and HPLC. Following a single i.v. dose, decay of total tritium in plasma was tetraphasic, with a rapid initial t1/2 alpha of 0.044 +/- 0.013 h, followed by a t1/2 beta of 0.54 +/- 0.22 h and a t1/2 gamma of 9.48 +/- 4.89 h; the terminal t1/2 gamma was 219 +/- 57 h. The mean plasma clearance of total tritium was 0.054 +/- 0.044 l.kg/h, and the mean volume of distribution was 14.3 +/- 5.4 l/kg; mean urinary excretion was 13.6% +/- 4.3% of the delivered radioactivity. Qualitative analysis of plasma and urine revealed the predominance of unchanged VZL plus two unidentified metabolites with different elution times. In comparison with oral VZL, as previously reported, i.v. injected VZL showed comparable values with respect to the volume of the central compartment (VC), plasma clearance (Clp), and terminal t1/2 for total tritium. Qualitatively, the metabolites observed in plasma and urine were comparable in number and quantity with values obtained in analyses after oral administration.

Antineoplastic Agents, Phytogenic↗