Search PubMed⌕ Search

Biomedical subjects

R McDonald

Publications and source records attributed to R McDonald.

At least 37 records · Page 2Linked to original sources
PubMed2001

Rejection profile of recent pediatric renal transplant recipients compared with historical controls: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).

Historically, higher acute rejection rates, earlier first rejection, and an inability to reverse the rejection characterize pediatric renal transplantation. In recent years, short-term (1-year) graft survival of pediatric renal transplants has steadily improved. To test the hypothesis that these improvements were mediated by changes in acute rejection, we considered the rejection profile of patients who received a renal allograft between 1987 and 1989 (cohort A) and compared it with recipients transplanted between 1997 and 1999 (Cohort B). Cohort A comprised 1469 transplants and cohort B comprised 1189 transplants. Restricting the data to the first year of follow-up, rejection ratios were 1.6 and 0.7, respectively (p < 0.001). Sixty per cent of the later cohort (B) were rejection free at 1 year, compared with 29% for the earlier cohort (A) (p < 0.001). Controlling for donor source, the rejection reversal rate for the later cohort was significantly better than that of the early cohort (p < 0.001). Cumulative distribution of times to first rejection was significantly better for cohort B (p < 0.001). One-year graft survival for cohort B at 94% was significantly better than 80% for cohort A (p < 0.001). We conclude that the improved short-term graft survival is mediated by improvements in the rejection profile in more recently transplanted patients and that this may translate into a better half-life for pediatric renal transplant recipients who received an allograft in the years 1997-99.

Adolescent↗
PubMed2001

Reducing conduct problems among children of battered women.

This study was an experimental evaluation of an intervention designed to reduce conduct problems among children of battered women. Participants were 36 families (mothers and children) in which the mother had sought shelter because of relationship violence and had at least 1 child (4-9 years old) with clinical levels of conduct problems. The intervention consisted of 2 primary components: (a) providing instrumental and emotional support and (b) teaching child management skills to mothers. Families were randomly assigned to either the intervention condition or the existing services comparison condition and were assessed on 5 occasions over 16 months after shelter departure. Compared with families receiving existing services, children in the intervention condition improved at a faster rate, the proportion of children displaying clinical levels of conduct problems was greatly diminished, and mothers displayed greater improvements in child management skills.

Battered Women↗
PubMed2001

Managing the entry of new medicines in the National Health Service: health authority experiences and prospects for primary care groups and trusts.

For the most part, the management of new medicines in the NHS has hitherto been a matter for local discretion. The result is that access to medicines is often determined by where a patient lives, as opposed to some nationally agreed clinical criteria. This "postcode prescribing" has led to widespread variations in access to medicines and concerns about the resulting inequalities. Primary care groups and trusts are expected to reduce variations in access to care, whilst at the same time balancing their finances, since any overspends on prescribing must be covered by disinvestment in hospital and community services. We interviewed 21 health authority (HA) prescribing advisers to ascertain how they viewed the managed entry of new medicines in order to identify lessons for PCGs. In addition, we report the views of local prescribing managers on the potential impact of recent government policy changes on the process and speculate on the likely implications of these for primary care groups and trusts. What is clear from the study is that HAs often have no explicit objective in relation to new medicines, but that their desire to act is prompted by fears of overspending on prescribing budgets. The danger of this approach is that patients may be denied cost-effective treatments since all new medicines are seen as a problem. It seems likely that PCG/Ts will face the same dilemmas with which the HA advisers in our study have been wrestling for some time. Recent policy changes in relation to prescribing budgets and new medicines are likely to exacerbate these problems. The tensions between local priority setting, which may mean saying no to new medicines, whilst at the same time eradicating postcode prescribing and balancing budgets means that PCG/Ts face difficult policy choices.

Budgets↗
PubMed2001

Multiplexing for the detection of multiple biowarfare agents shows promise in the field.

Standard amplification of nucleic acids, or polymerase chain reaction (PCR), is replacing the more traditional microbiological assays in the detection of biological agents. However, standard PCR is designed as a one program-to-one agent amplification method, and not knowing what agents to test for makes this approach time consuming. During a field training exercise to detect four biowarfare agents using the standard PCR method, we conducted an additional experiment that reduced the diagnostic time to one-fourth. By reprogramming the four amplification programs to one program and preparing a cocktail containing the four different primer sets for the agents (known as multiplexing, or mPCR), we were able to amplify the four genetically different biological agents simultaneously. This is the first time a military unit has performed this kind of field testing, and it shows promise for the early detection of multiple biowarfare agents.

Bacillus anthracis↗
PubMed2000

Bimolecular extrusion of TeR2 from beta-diketiminato supported scandium bis-tellurolates.

Reaction of the well-defined, base-free dialkyl scandium compounds LnSc(CH2SiMe3)2 supported by the beta-diketiminato ligands ArNC(R)CHC(R)NAr (Ar = 2,6-diisopropyl; R = Me, L1: R = tBu, L2) with two equivalents of nBuP = Te gives the bis-tellurolate complexes LnSc(TeCH2SiMe3)2, 1b (L1) and 2b (L2). Tellurolate 2b was isolated and fully characterized, including an X-ray structure analysis, and exhibits two chemically distinct tellurolate ligands in solution on the NMR time scale. Tellurolate 1b is only moderately stable and decomposes with elimination of two equivalents of Te(CH2SiMe3)2 to form the dimeric bis-telluride 1d. This compound was characterized by X-ray crystallography and elemental analysis. In contast, tellurolate 2b decomposes with loss of only one equivalent of Te(CH2SiMe3)2, leading to the formation of a dinuclear complex with one bridging telluride unit joining two L2Sc(TeCH2SiMe3) fragments. This compound was also structurally characterized. The solution behavior of this material is complex, as it exists as three conformational isomers that undergo slow exchange on the NMR time scale. The production of dimer 2c, along with the results of crossover experiments, suggest strongly that TeR2 elimination from these bis-tellurolates is bimolecular.

Journal Article↗
PubMed2000

Ternary early-transition-metal palladium pnictides Zr3Pd4P3, Hf3Pd4P3, HfPdSb, and Nb5Pd4P4.

Several ternary palladium pnictides of the early transition metals have been prepared by arc-melting of the elemental metals and the binary pnictides ZrP, HfP, HfSb2, or NbP, and their structures have been determined by X-ray diffraction methods. The phosphides M3Pd4P3 (M = Zr, Hf) adopt a new structure type (Pearson symbol oP40), crystallizing in the orthorhombic space group Pnma with Z = 4 and unit cell parameters of a = 16.387(2), b = 3.8258(5), and c = 9.979(1) A for Zr3Pd4P3 and a = 16.340(2), b = 3.7867(3), and c = 9.954(1) A for Hf3Pd4P3. The antimonide HfPdSb was identified by powder X-ray diffraction (orthorhombic, Pnma, Z = 4, a = 6.754(1) A, b = 4.204(1) A, and c = 7.701(2) A) and confirmed to be isostructural to ZrPdSb, which adopts the TiNiSi-type structure. The phosphide Nb5Pd4P4 adopts the Nb5Cu4Si4-type structure, crystallizing in the tetragonal space group I4/m with Z = 2, a = 10.306(1) A, and c = 3.6372(5) A. Coordination geometries of pentacapped pentagonal prisms for the early transition metal, tetracapped distorted tetragonal prisms for Pd, and tricapped trigonal prisms for the pnicogen are found in the three structures; tetracapped tetragonal prisms for Nb are also found in Nb5-Pd4P4. In common with many metal-rich compounds whose metal-to-nonmetal ratio is equal or close to 2:1, the variety of structures formed by these ternary palladium pnictides arises from the differing connectivity of pnicogen-filled trigonal prisms. Pnicogen-pnicogen bonds are absent in these structures, but metal-metal bonds (in addition to metal-pnicogen bonds) are important interactions, as verified by extended Hückel band structure calculations on Zr3Pd4P3.

Journal Article↗
PubMed2000

Chiral discrimination in hydrogen-bonded

A series of racemic [7]helicenes have been prepared and characterized both in solution and in the solid state. Despite the helicenes having the ability to self-assemble in a variety of stereochemical and topological relationships, they formed only enantiomerically pure dimers held together by two pairs of cooperative hydrogen bonds. The self-assembly process was enantiospecific in solution and diastereoselective in the crystal.

Journal Article↗
PubMed2000

GM-CSF regulates bleomycin-induced pulmonary fibrosis via a prostaglandin-dependent mechanism.

To characterize the role of GM-CSF in pulmonary fibrosis, we have studied bleomycin-induced fibrosis in wild-type mice vs mice with a targeted deletion of the GM-CSF gene (GM-CSF-/- mice). Without GM-CSF, pulmonary fibrosis was worse both histologically and quantitatively. These changes were not related to enhanced recruitment of inflammatory cells because wild-type and GM-CSF-/- mice recruited equivalent numbers of cells to the lung following bleomycin. Interestingly, recruitment of eosinophils was absent in GM-CSF-/- mice. We investigated whether the enhanced fibrotic response in GM-CSF-/- animals was due to a deficiency in an endogenous down-regulator of fibrogenesis. Analysis of whole lung homogenates from saline- or bleomycin-treated mice revealed that GM-CSF-/- animals had reduced levels of PGE2. Additionally, alveolar macrophages were harvested from wild-type and GM-CSF-/- mice that had been exposed to bleomycin. Although bleomycin treatment impaired the ability of alveolar macrophages from wild-type mice to synthesize PGE2, alveolar macrophages from GM-CSF-/- mice exhibited a significantly greater defect in PGE2 synthesis than did wild-type cells. Exogenous addition of GM-CSF to alveolar macrophages reversed the PGE2 synthesis defect in vitro. Administration of the PG synthesis inhibitor, indomethacin, to wild-type mice during the fibrogenic phase postbleomycin worsened the severity of fibrosis, implying a causal role for PGE2 deficiency in the evolution of the fibrotic lesion. These data demonstrate that GM-CSF deficiency results in enhanced fibrogenesis in bleomycin-induced pulmonary fibrosis and indicate that one mechanism for this effect is impaired production of the potent antifibrotic eicosanoid, PGE2.

Animals↗
PubMed2000

Transplantation of adult living donor kidneys into infants and small children.

HYPOTHESIS: We hypothesized that improved outcomes following renal transplantation in high-risk infants and small children primarily are due to advances in immunosuppression and accurate diagnosis of rejection. Optimizing renal allograft perfusion is critical to achieving good early graft function and decreasing early graft loss. DESIGN: Twenty-eight consecutive recipients (weighing <20 kg) of adult living donor kidneys transplanted at our center from 1984 to 1999 were reviewed. Two groups were identified based on differing immunosuppression protocols and clinical surveillance. Actuarial graft and patient survival reported at 1, 3, and 5 years were compared for group 1 (1984-1991) and group 2 (1992-1999). Graft losses, categorized as immunologic or nonimmunologic, and the incidences of delayed graft function, vascular thrombosis, and rejection were compared. RESULTS: Graft and patient survival in group 1 (n = 13) at 1, 3, and 5 years was 77% and 92%, 54% and 85%, and 54% and 85%, respectively. In group 2, all 15 patients are alive with functioning grafts to date. Immunologic graft loss occurred in 5 of 13 patients in group 1 who developed chronic rejection. Nonimmunologic causes (vascular thrombosis [2 patients]) and patient death [1]) resulted in early graft failure within 2 weeks in 3 of 13 patients in group 1. The overall incidences of delayed graft function (10.7%) and thrombosis (7.1%) were low and did not differ between groups. Percutaneous renal biopsy was used more frequently in group 2 to evaluate graft dysfunction and guide treatment. CONCLUSIONS: We conclude that improved overall graft and patient survival in group 2 is owing to advances in immunosuppression and better treatment of rejection. Percutaneous renal biopsy allows prompt and accurate histological diagnosis of graft dysfunction. Surgical technique and aggressive fluid management aimed at maximizing renal allograft perfusion is critical in optimizing early graft function and decreasing vascular complications.

Adult↗
PubMed2000

Versatile precursor to ruthenium-bis(phosphine) hydrogenation catalysts.

The known complex trans-RuCl2(NBD)Py2 (1, NBD is norbornadiene, Py is pyridine) reacts with either (R)-BINAP ((R)-2, 2'-bis(diphenylphosphino)-1,1'-binaphthyl), (S;S)-Chiraphos ((2S;3S-(-)-2,3-bis(diphenylphosphino)butane), (S;S)-Skewphos ((2S;4S)-(-)-2,4-bis(diphenylphosphino)pentane), (R)-(S)-Josiphos ((R)-(-)-1-[(S)-2-(diphenylphosphino)ferrocenyl]ethyl-dicyclohexylpho sphine), (R;R)-Norphos ((2R;3R)-(-)-2, 3-bis(diphenylphosphino)bicyclo[2.2.1]hept-5-ene), or (R;R)-Me-DUPHOS ((-)-1,2-bis((2R;5R)-2, 5-dimethylphospholano)benzene) to generate in high yields the crystalline complexes trans-RuCl2(P-P*)Py2 (P-P* is the corresponding chiral bis(phosphine)). The complexes trans-RuCl2(P-P*)Py2 are active enantioselective hydrogenation catalysts for ketoesters and noncarboxylic olefins in the presence of small amounts of HBF4 (aq.). They are active for hydrogenation of carboxylic substrates in the presence of Et3N. Reaction of trans-RuCl2(P-P*)Py2 with (rac)-1,2-diphenylethylene-diamine (N-N*, either enantiomer) forms in good yields the corresponding compounds trans-RuCl2(P-P*)(N-N*). Representative hydrogenations with these catalysts are presented.

Journal Article↗
PubMed2000

Serologic markers for Chlamydia pneumoniae in asthma.

BACKGROUND: Chlamydia pneumoniae infection has been reported as a possible etiologic agent in asthma, which in primary care settings often appears to be initiated by acute respiratory infections. OBJECTIVE: To determine if serologic markers for C. pneumoniae are associated with adult asthma that first became symptomatic after an acute respiratory illness (asthma associated with infection: AAWI). METHODS: Serum samples from 164 primary care outpatients, mean age 44 years, (68 with AAWI; 36 with atopic, occupational or exercise-induced asthma (non-AAWI); 16 nonasthmatic patients with acute bronchitis; and 44 asymptomatic nonasthmatic controls) were tested for the presence of C. pneumoniae-specific IgG and IgA antibodies. Levels of chlamydial heat shock protein 60 (CHSP60) antibody were also measured. Those positive for CHSP60 were tested for C. pneumoniae-specific IgE antibodies by immunoblotting. RESULTS: Statistically significant differences in IgG and IgA seroreactivity were noted between groups: acute bronchitis and AAWI had the highest levels (93% to 94% IgG seroreactivity, 69% to 75% IgA seroreactivity) whereas non-AAWI and asymptomatic controls had the lowest levels (61% to 84% IgG seroreactivity, 31% to 43% IgA seroreactivity, P < .02 after adjustment for age, sex and smoking). CHSP60 antibodies were significantly more prevalent in AAWI than in non-AAWI (19% versus 3%, P = .02). IgE antibodies against C. pneumoniae 60, 62, and/or 70 kD antigens were detected in 5 of 13 CHSP60 positive AAWI patients. Persistent IgG, IgA, and CHSP60 seroreactivities were noted in all seropositive asthma patients with serial serum samples. CONCLUSIONS: Serologic markers of C. pneumoniae infection were associated with acute bronchitis and with asthma that first became symptomatic following respiratory illness. Serologic responses to C. pneumoniae may be useful in the classification and diagnosis of asthma.

Adult↗
PubMed2000

A decade of living donor transplantation in North American children: the 1998 annual report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).

This report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) covers the years 1987-1997, and analyzes data on 2,904 living donor (LD) transplants performed in 2,779 patients. Since 1991, approximately 300 LD transplants have been performed each year at the participating centers of the NAPRTCS. Caucasian children account for 72% of all LD recipients while African-American children constitute only 11%. There has been a gradual decline in the number of transplants performed in children under the age of 6 years from a peak of 30% in 1987, to 21% in 1997. Preoperative calcineurin inhibitor therapy has dropped from 71% in 1987 to 38% in 1997. Through 1996, at six months post-transplant 97% of recipients were receiving prednisone, 88% were maintained on cyclosporin A, and 79% were receiving azathioprine. Of patients transplanted in 1997, 47% are maintained on mycophenolate and 10% are maintained on tacrolimus. By day 15, 20% of index transplant patients have had an acute rejection and by the end of the first year 47% have had a rejection episode. Among patients transplanted in 1995-1996, 40% had a rejection in the first year. Nine per cent of rejection episodes are irreversible in children under 2 years of age and 5% of the episodes are irreversible in 25-year-old children. Estimated graft survival probability at 1 year is 91%, at 3 years it is 84% and at 5 years it is 78.5%. Rejection accounts for 33% of graft loss and recurrence constitutes another 10%. Influential prognostic variables for graft survival are race (African-American vs. others, relative risk (RR) = 2.0, p < 0.001), > 5 random transfusions (RR = 1.6, p < 0.001, T cell induction therapy (RR = 0.78, p = 0.01), and later year of entry (1989-1990 vs. 1994-1995, RR = 0.95, p = 0.04). Patient survival at 1 and 3 years was 97% and 96.5%, respectively, however, the 3-year patient survival of children under 2 years was 89%. The mean height deficit baseline (n=2,677) was -1.86, at 1 year post-transplant (n=1,459) it was -1.80, and at 5 years post-transplant (n=592) it was -2,06. This report, devoted specifically to LD pediatric transplants, raises the issues regarding the use of immunosuppression such as preoperative calcineurin inhibitors and T-cell antibodies. Studies to address the high incidence of chronic rejection and recurrence of original disease are necessary. Additional areas of concern are the high infant mortality and continued growth retardation post-transplantation.

Adolescent↗
PubMed2000

Patterns of adjustment among children of battered women.

Children exposed to interparental violence have been characterized by an array of psychological problems, but findings regarding the precise nature of these problems have been inconsistent. This study used cluster analysis to determine whether distinct patterns of adjustment could be identified in 228 8- to 14-year-old children residing in battered women's shelters. Five such patterns emerged: multiproblem-externalizing, multiproblem-internalizing, externalizing, mild distress, and no problems reported. This solution was cross-validated in independent halves of the sample and was similar for boys and girls. Differences among the clusters on relevant family and demographic variables were examined, and it was found that the clusters could be distinguished on the basis of the frequency of children's exposure to interparental violence, parent-child aggression, and children's appraisals of interparental conflict.

Adaptation, Psychological↗
PubMed2000

Involvement of the medial septum in stress-induced relapse to heroin seeking in rats.

Intermittent footshock stress has been shown to reinstate extinguished drug-taking behaviour in rats, but the brain areas involved in this effect are to a large degree unknown. Here we studied the role of the septum in stress-induced reinstatement of heroin seeking. Rats were trained to self-administer heroin for 9-10 days (three 3-h sessions per day, 0.1 mg/kg per infusion). Following training, extinction sessions were given for 8-13 days by substituting saline for heroin, and then tests for reinstatement of heroin seeking were carried out. Reversible inactivation of the medial septum with tetrodotoxin (TTX; 1-5 ng, infused 25-40 min before the test sessions) reliably reinstated heroin seeking, mimicking the effect of 15 min of intermittent footshock. This effect of TTX was not observed after infusions made 1.5 mm dorsally into the lateral septum. In other experiments, it was found that infusions of a low, subthreshold dose of TTX (0.5 ng) into the medial septum, when combined with 2 min of footshock that in itself was ineffective, reinstated heroin seeking. Furthermore, electrical stimulation (400 microA pulses, 100 micros duration, 100 Hz frequency) of the medial septum during exposure to 10 min of intermittent footshock attenuated footshock-induced reinstatement of heroin seeking. These data suggest a role for the medial septum in stress-induced relapse to drug seeking. The septum is thought to be involved in neuronal processes underlying behavioural inhibition, thus we speculate that stressors provoke relapse by interfering with these processes.

Animals↗
PubMed1999

Stabilization of a Discrete Lanthanide(II) Hydrido Complex by a Bulky Hydrotris(pyrazolyl)borate Ligand.

Divalent and solvent-free: the ytterbium hydrido complex 1 was obtained by the hydrogenolysis of [(Tp(tBu,Me))Yb(CH(2)SiMe(3))(thf)]. The steric demand of the bulky hydrotris(3-tert-butyl-5-methylpyrazolyl)borate ligand, Tp(tBu,Me), is sufficient to stabilize the dimer, yet facile room-temperature reactions with amines, alkynes, diynes, and CO indicate a rich chemistry of 1.

Journal Article↗