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Biomedical subjects

D J Gallagher

Publications and source records attributed to D J Gallagher.

14 recordsLinked to original sources
PubMed2000

Synthesis of highly potent second-generation taxoids through effective kinetic resolution coupling of racemic beta-lactams with baccatins.

A series of highly potent second-generation taxoids bearing a 2-methylprop-1-enyl or a 2-methylpropyl group at C-3' with modifications at the C-2, C-10, and C-14 positions was synthesized through the coupling of racemic cis-beta-lactams with properly protected/modified baccatin and 14-OH-baccatin. A high level of kinetic resolution was observed for all cases examined. The observed highly efficient enantiomer differentiation is ascribed to the markedly different chiral environment between the (+)- and (-)-beta-lactams in their approach to the chiral framework of the enantiopure lithium alkoxide of a baccatin in the ring-opening coupling process. It was also observed that substantially higher selectivity was achieved when 14-OH-baccatin-1,14-carbonate was used. Analysis of the transition state models revealed that the repulsive interactions between the 3-TIPS group of a (-)-beta-lactam with 1, 14-carbonate group of the baccatin substantially increases the asymmetric bias in the kinetic resolution process, favoring the reaction of a (+)-beta-lactam, which leads to the observed excellent selectivity.

Alkaloids↗
PubMed1999

Phosphorylation is required for alteration of kv1.5 K(+) channel function by the Kvbeta1.3 subunit.

The Kv1.5 K(+) channel is functionally altered by coassembly with the Kvbeta1.3 subunit, which induces fast inactivation and a hyperpolarizing shift in the activation curve. Here we examine kinase regulation of Kv1.5/Kvbeta1.3 interaction after coexpression in human embryonic kidney 293 cells. The protein kinase C inhibitor calphostin C (3 microM) removed the fast inactivation (66 +/- 1.9 versus 11 +/- 0.25%, steady state/peak current) and the beta-induced hyperpolarizing voltage shift in the activation midpoint (V(1/2)) (-21.9 +/- 1.4 versus -4.3 +/- 2.0 mV). Calphostin C had no effect on Kv1.5 alone with respect to inactivation kinetics and V(1/2). Okadaic acid, but not the inactive derivative, blunted both calphostin C effects (V(1/2) = -17.6 +/- 2.2 mV, 38 +/- 1.8% inactivation), consistent with dephosphorylation being required for calphostin C action. Calphostin C also removed the fast inactivation (57 +/- 2.6 versus 16 +/- 0.6%) and the shift in V(1/2) (-22.1 +/- 1.4 versus -2.1 +/- 2.0 mV) conferred onto Kv1.5 by the Kvbeta1.2 subunit, which shares only C terminus sequence identity with Kvbeta1. 3. In contrast, modulation of Kv1.5 by the Kvbeta2.1 subunit was unaffected by calphostin C. These data suggest that Kvbeta1.2 and Kvbeta1.3 subunit modification of Kv1.5 inactivation and voltage sensitivity require phosphorylation by protein kinase C or a related kinase.

Cell Line↗
PubMed1998

Distinct domains of the voltage-gated K+ channel Kv beta 1.3 beta-subunit affect voltage-dependent gating.

The Kvbeta1.3 subunit confers a voltage-dependent, partial inactivation (time constant = 5.76 +/- 0.14 ms at +50 mV), an enhanced slow inactivation, a hyperpolarizing shift in the activation midpoint, and an increase in the deactivation time constant of the Kv1.5 delayed rectifier. Removal of the first 10 amino acids from Kvbeta1.3 eliminated the effects on fast and slow inactivation but not the voltage shift in activation. Addition of the first 87 amino acids of Kvbeta1.3 to the amino terminus of Kv1.5 reconstituted fast and slow inactivation without altering the midpoint of activation. Although an internal pore mutation that alters quinidine block (V512A) did not affect Kvbeta1.3-mediated inactivation, a mutation of the external mouth of the pore (R485Y) increased the extent of fast inactivation while preventing the enhancement of slow inactivation. These data suggest that 1) Kvbeta1.3-mediated effects involve at least two distinct domains of this beta-subunit, 2) inactivation involves open channel block that is allosterically linked to the external pore, and 3) the Kvbeta1.3-induced shift in the activation midpoint is functionally distinct from inactivation.

Action Potentials↗
PubMed1997

Biomechanical analysis of nonreamed tibial intramedullary nailing after simulated transverse fracture and fibulectomy.

A tibial shaft fracture model was created to study the effects of an intramedullary nail and partial fibulectomy on fracture loading. Cadaveric lower extremities were instrumented with strain gages and subjected to biomechanical testing. A nonreamed nail was inserted into each tibia using only the proximal locking screws. Each specimen was tested under six conditions: intact tibia; intact tibia with nail; fractured tibia with nail removed and fibula intact; fractured tibia with nail and fibula intact; fractured tibia with nail and partial fibulectomy; and fractured tibia with partial fibulectomy and nail removed. In the intact tibia the anterior cortices were in relative tension compared with the posterior cortex. After transverse fracture this relative tension was increased. Inserting the nail after fracture significantly increased anteromedial and anterolateral compressive strains and decreased posterior strains. Performing a partial fibulectomy in the fractured tibia with a nail had no significant effect on the strain patterns. These results confirm the relative anterior tension present in the intact tibia and demonstrate an increase in this anterior tension following transverse fracture. Performing a partial fibulectomy or inserting an intramedullary nail increased anterior compressive loading. This loading alteration may be responsible for the clinical success seen using these treatment methods.

Analysis of Variance↗
PubMed1996

Orthopedic manifestations of acute pediatric leukemia.

The variety and distribution of skeletal lesions in children with acute lymphoblastic leukemia is rarely seen in other diseases. Skeletal radiographic changes that can occur in a child with acute leukemia include diffuse osteopenia, metaphyseal bands, periosteal new bone formation, geographic osteolysis, osteosclerosis, mixed osteolysis and sclerosis, and permeative destruction. It is important for orthopedic surgeons to recognize the skeletal manifestations of acute leukemia of childhood because the physician who initially evaluates the child will often be an orthopedic surgeon, and a delay in diagnosis has an adverse affect on survival.

Acute Disease↗
PubMed1990

Pediatric chance fracture.

A flexion-distraction injury of the first lumbar vertebrae (Chance fracture) in a child 4 years and 3 months old is discussed and the literature reviewed. Chance features are uncommon in children. This injury is seldom accompanied by a neurological deficit. Recommended treatment consists of early bed rest followed by the application of a hyperextension Risser cast.

Abdominal Injuries↗
PubMed1986

Prophylaxis against vitamin D deficiency in the elderly by regular sunlight exposure.

The effects of regular sunlight exposure on levels of vitamin D metabolites and on other indices of calcium metabolism have been studied in elderly rest-home residents. Fifteen subjects who formerly went outdoors very infrequently were studied over a 4-week period while spending 0, 15 or 30 minutes daily sitting on the rest-home verandah. During this time, levels of 25-hydroxyvitamin D [25(OH)D] rose by 7.4 +/- 1.2 (s.e.m.) microgram/1 in the group spending 30 minutes per day outdoors (P less than 0.005) and there was a smaller but nonsignificant increase in the 15 minutes per day group also. Serum 1,25 (OH)2D levels did not change during the study but serum ionized calcium and alkaline phosphatase showed small, but significant, decreases. Intestinal strontium absorption increased in both treatment groups (P less than 0.05), indicating a similar change in calcium absorption. It is concluded that 30 minutes spent outdoors each day leads to a substantial increase in 25(OH)D levels in elderly subjects and that this has significant effects upon other indices of calcium metabolism. This regimen provides a safe and inexpensive method for the prevention of osteomalacia in frail elderly subjects.

Aged↗
PubMed1976

A new tetracycline minocycline compared with ampicillin in general practice.

A new tetracycline (minocycline) and ampicillin were compared in the treatment of 217 adults with common infections seen in general practice. Minocycline had an overall clinical effectiveness comparable with ampicillin, though minocycline was more frequently prescribed for suspected staphylococcal infections with satisfactory results in 25 (26). Minocycline was significantly more effective in vitro against common pathogenic organisms than ampicillin. All strains of staphyloccocci isolated were sensitive to minocycline while 15 (27) were resistant to ampicillin. Minocycline and ampicillin were no different in the occurrence of mild side effects. Dizziness was troublesome for 23 (127) patients on minocycline and resulted in four patients discontinuing treatment.

Adult↗
PubMedDate not supplied

Universal precautions--do Irish anaesthetists comply?

BACKGROUND: Anaesthetists are at high risk from blood-borne pathogens. Universal Precautions (UP) include the routine use of appropriate barrier precautions and techniques to reduce the likelihood of exposure to blood, body fluids and tissues that may contain pathogens. The compliance of Irish anaesthetists with these precautions has not been studied. AIM: To study the attitudes of Irish anaesthetists to Universal Precautions. METHOD: A postal questionnaire was sent to 210 anaesthetists currently practising in Ireland. The questionnaire was based on a model used in Australia and New Zealand. RESULTS: There was a 50% response rate to the survey. Only 15% of respondents had taken a risk history from a patient in the preceding four weeks. Resheathing of needles was commonplace. The effectiveness of hepatitis B immunisation was rarely checked and only 66% of respondents believe implementation of Universal Precautions to be practical. CONCLUSION: Irish anaesthetists comply poorly with Universal Precautions.

Anesthesiology↗