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Biomedical subjects

J Freeman

Publications and source records attributed to J Freeman.

At least 181 records · Page 10Linked to original sources

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↗

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↗

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↗

Inhibition of HIV replication by Hyssop officinalis extracts.

Crude extracts of dried leaves of Hyssop officinalis showed strong anti-HIV activity as measured by inhibition of syncytia formation, HIV reverse transcriptase (RT), and p17 and p24 antigen expression, but were non-toxic to the uninfected Molt-3 cells. Ether extracts from direct extraction (Procedure I), after removal of tannins (Procedure II), or from the residue after dialysis of the crude extract (Procedure III), showed good antiviral activity. Methanol extracts, subsequent to ether, chloroform and chloroform ethanol extractions, derived from procedure I or II, but not III, also showed very strong anti-HIV activity. In addition, the residual material after methanol extractions still showed strong activity. Caffeic acid was identified in the ether extract of procedure I by HPLC and UV spectroscopy. Commercial caffeic acid showed good antiviral activity in the RT assay and high to moderate activity in the syncytia assay and the p17 and p24 antigen expression. Tannic acid and gallic acid, common to other teas, could not be identified in our extracts. When commercial products of these two acids were tested in our assay systems, they showed high to moderate activity against HIV-1. Hyssop officinalis extracts contain caffeic acid, unidentified tannins, and possibly a third class of unidentified higher molecular weight compounds that exhibit strong anti-HIV activity, and may be useful in the treatment of patients with AIDS.

Antiviral Agents↗

The iliac crest and the radial forearm flap in vascularized oromandibular reconstruction.

Sixty cases (59 patients) of oromandibular reconstruction using vascularized iliac crests were compared with 13 in which radial osteocutaneous flaps were used. These patients were reviewed from the standpoint of cosmetic results and function as well as their operative and postoperative courses. In both groups, the results were generally good. However, revisionary surgery was more frequent in those receiving the iliac crest. This group also had a higher incidence of intraoral wound breakdown and bone exposure. Nevertheless, the sheer size of the iliac crest made it ideal for massive oromandibular defects, just as its natural curvature lent itself to precise replication of the mandible in bone-only reconstructions. Its bulk proved a major obstacle in small composite defects. The radial forearm flap carried thin, pliable, well-vascularized skin that was superior to groin skin for oral lining. Bone gaps of up to 9 cm could be handled with ease, thus making it complementary to the iliac crest over the wide spectrum of mandibular reconstruction.

Adolescent↗

[Flumazenil and peroperative awakening in surgery of scoliosis].

Motor and sensory function must be assessed during surgery of scoliosis so as to avoid possible damage to the spinal cord. The intraoperative awakening by a specific benzodiazepine antagonist, flumazenil, was studied prospectively in 20 patients (mean age 17 years) undergoing surgery for severe scoliosis. Premedication consisted in 0.02 mg.kg-1 atropine and 0.15 mg.kg-1 midazolam. Anaesthesia was induced with a mean dose of 0.42 +/- 0.1 mg.kg-1 midazolam, 1.6 +/- 0.6 micrograms.kg-1 fentanyl and 0.1 mg.kg-1 pancuronium. Maintenance was obtained with a continuous infusion of 0.22 +/- 0.1 mg.kg-1.h-1 midazolam, 66% nitrous oxide in oxygen, and fentanyl (1.6 +/- 0.5 micrograms.kg-1.h-1). Nitrous oxide and midazolam were respectively stopped 10 and 1 min before giving the antagonist (5 micrograms.kg-1 flumazenil) if required (17 out of the 20 patients). Eye opening occurred a mean 42 +/- 32 s after giving the antagonist. At this time, there was a significant increase in mean arterial blood pressure (+ 11 mmHg) and heart rate (+ 7 b.min-1). Thiopentone, 66% nitrous oxide in oxygen and 0.5% halothane were given to re-induce and maintain anaesthesia for completion of the procedure. The day following surgery, 19 patients were unable to remember the period of intraoperative awakening. One patient, although remembering the episode, did not experience any pain or any other disagreement in relation to it. Two patients were given a second dose of flumazenil at extubation so as to improve the quality of their recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Plasmid DNA fingerprinting of Acinetobacter calcoaceticus subspecies anitratus from intubated and mechanically ventilated patients.

Forty-three intubated and mechanically ventilated patients in five intensive care units (ICUs) of one hospital developed respiratory colonization or infection with Acinetobacter calcoaceticus subspecies anitratus over a 16-month interval. Neither the frequency nor rate of A anitratus isolation exceeded the hospital endemic norms. Single isolates from 34 of the patients were subtyped by plasmid DNA analysis, two biotyping systems and antimicrobial susceptibility to 24 drugs. Plasmid DNA fingerprints were distinct in 18 isolates (they differed from each other and all others), similar in two and identical or similar in ten. The latter group of isolates were recovered from patients in four ICUs. Reproducibility of biotyping was poor. Neither biotyping nor antimicrobial susceptibility were successful in identifying sameness among the group isolates nor differences among other isolates. We conclude that plasmid DNA fingerprinting should be used to assess the possibility of multiple patient transmissions of the same A anitratus strain in the absence of an obvious outbreak.

Acinetobacter↗

Birth weight and length of stay as determinants of nosocomial coagulase-negative staphylococcal bacteremia in neonatal intensive care unit populations: potential for confounding.

Coagulase-negative staphylococci are the most common cause of bacteremia in the neonatal intensive care units of the Brigham and Women's Hospital and the Children's Hospital, Boston, Massachusetts. In 1982, nosocomial bacteremia with coagulase-negative staphylococci occurred in 45 of 882 (5.1%) infants admitted to these units who survived and remained in intensive care for more than 48 hours and were therefore at risk. The overall cumulative incidence (attack rate) of nosocomial bacteremia rose dramatically with decreasing birth weight. The smallest infants, those with birth weights of less than 750 g, experienced an overall risk of nosocomial bacteremia 44.5 times that of infants with birth weights of greater than 2,000 g. A large part of the excess risk for small babies was attributable to their longer hospitalizations. However, after adjustment for length of stay, the smallest infants still suffered a daily rate of bacteremia (incidence density) 5.3 times that of the largest, indicating a considerable residual effect of birth weight on the daily risk of nosocomial coagulase-negative staphylococcal bacteremia. The results were similar in the two nurseries. Thus, there is still a substantially increased intrinsic risk of nosocomial coagulase-negative staphylococcal bacteremia among infants with very low birth weights, even after adjustment for duration of hospitalization, and differences in birth weight can confound comparative studies.

Birth Weight↗

Nuclear factors interact with conserved A/T-rich elements upstream of a nodule-enhanced glutamine synthetase gene from French bean.

The gln-gamma gene, encoding the gamma subunit of glutamine synthetase in French bean (Phaseolus vulgaris), is strongly induced during nodule development. We have determined the nucleotide sequence of a 1.3-kilobase region at its 5' end and have identified several sequences common to the promoter regions of late nodulin genes from other legume species. The 5'-flanking region was analyzed for sequence-specific interactions with nuclear factors from French bean. A factor from nodules (PNF-1) was identified that binds to multiple sites between -860 and -154, and a related but distinct factor (PRF-1) was detected in extracts from uninfected roots. PNF-1 and PRF-1 bound strongly to a synthetic oligonucleotide containing the sequence of an A/T-rich 21-base pair imperfect repeat found at positions -516 and -466. The same factors also had a high affinity for a protein binding site from a soybean leghemoglobin gene and appeared to be closely related to the soybean nodule factor NAT2, which binds to A/T-rich sequences in the lbc3 and nodulin 23 genes [Jacobsen et al. (1990). Plant Cell 2, 85-94]. Comparison of NAT2/PNF-1 binding sites from a variety of nodulin genes revealed the conservation of the short consensus core motif TATTTWAT, and evidence was obtained that this sequence is important for protein recognition. Cross-recognition by PNF-1 of a protein binding site in a soybean seed protein gene points to the existence of a ubiquitous family of factors with related binding affinities. Our data suggest that PNF-1 and PRF-1 belong to an evolutionarily conserved group of nuclear factors that interact with specific A/T-rich sequences in a diverse set of plant genes. We consider the possible role of these factors in coregulating the expression of gln-gamma and other late nodulin genes.

Amino Acid Sequence↗

Resection of the epileptogenic area in critical cortex with the aid of a subdural electrode grid.

Electrode grids were implanted subdurally in 28 patients with epilepsy. In 16 of the 28 patients, an epileptogenic area was located in the speech-dominant left temporal lobe. Recordings made with the grid revealed that the epileptogenic areas in the patients varied widely in extent: the area was confined within the first 10 mm of the temporal lobe in some patients or it was scattered throughout the entire anterior to posterior 80-mm extend in others. Resection of the epileptogenic area was adjusted accordingly in each case. In 6 of 16 patients who were left-hemisphere-dominant for language, up to 55-80 mm from the tip of the temporal lobe was removed, a measure that exceeds the conventional limit of 50 mm from the tip of the dominant hemisphere. In the remaining 12 of the 28 patients, epileptogenic areas were located in a combination of several lobes. In 7 of these 12 patients, the epileptogenic area encompassed the rolandic area; it was removed without deficit in 4 patients and with expected deficit in 3. Of the latter 3 patients, 1 patient underwent hemispherectomy, and a large portion of the epileptogenic rolandic cortex in the frontal and parietal lobes was removed from the other 2. There were 2 cases of grid-related infection, which cleared with antibiotic treatment; there were no lasting complications of grid implantation in any patient. There was no mortality. Electroencephalographic recording and functional mapping using subdural electrode grids allow a tailored, maximal resection of epileptogenic tissue with minimal injury to critical cortex.

Brain Diseases↗

Hyperbilirubinemia following exposure to pancuronium bromide in newborns.

We investigated the risk of hyperbilirubinemia in relation to the administration of pancuronium bromide among newborn infants requiring mechanical ventilation. One hundred and twenty-nine infants treated with pancuronium were compared to 129 infants who were never exposed, matched on ventilatory status, hospital, birthweight, initial total serum bilirubin, and date of hospital discharge. Overall, the adjusted summary relative risk (RR) for hyperbilirubinemia among pancuronium-exposed infants compared to nonexposed infants was 1.2 (95% confidence interval 1.1-1.4). The risk was greatest among exposed infants during the 4 days following the last dose of pancuronium (RR = 1.4; 1.0-1.8). These data suggest that the use of pancuronium in sick newborns may be associated with an increased risk of clinically important hyperbilirubinemia.

Bilirubin↗