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Biomedical subjects

A Smith

Publications and source records attributed to A Smith.

At least 181 records · Page 10Linked to original sources

Restricted use of antibiotic prophylaxis for recurrent acute otitis media in the era of penicillin non-susceptible Streptococcus pneumoniae.

OBJECTIVE/INTERVENTION: To compare the annual rates of acute otitis media (AOM) episodes, antibiotic days, and ventilating tube insertion during the first 3 years of life before and after a practice change to restrict use of antibiotic chemoprophylaxis for recurrent AOM. METHODS SETTING: The sole pediatric private practice in a rural Kentucky community. PATIENTS: Population-based sample of all children born consecutively in two different 13 month intervals. Cohort 1 (n=251) was born before and Cohort 2 (n=274) was born after restricted use of chemoprophylaxis and documented emergence of widespread penicillin non-susceptible Streptococcus pneumoniae (PNSP). DESIGN: Retrospective case cohort comparison. MAIN OUTCOME MEASURES: Suppurative AOM diagnosed by validated experienced otoscopists using stringent tympanic membrane criteria. RESULTS: Children were mostly white with the majority (50-65%) enrolled in daycare during each year. The first episode of AOM was experienced by 6 and 12 months of age in 64 and 86%, respectively. Rates of children with recurrent AOM in Cohorts 1 and 2 were 28 and 31% in Year 1, 17 and 23% in Year 2, and 7 and 10% in Year 3, respectively. Rates of new onset AOM and persistent AOM episodes were similar between cohorts in the first 2 years. Number of days of antibiotic prophylaxis were reduced from 11.2 to 3.4 days in Year 1, from 11.9 to 2.6 days in Year 2, and from 6.9 to 0.7 days in Year 3, respectively (P<0.0001 for each year). Total antibiotic days for Years 1, 2 and 3 were reduced commensurately with prophylactic days from 61.7 to 55.5 days (nonsignificant), from 56.3 to 45.8 days (P=0.047), and from 38.7 to 25.7 days (P<0.0001), respectively. For each year a non-significant trend for increased ventilating tube placement from Cohort 1 to Cohort 2, respectively, was observed, 2 versus 2.2%, 4 versus 5.8%, and 0.8 versus 2.6%. Daycare attendance and white race were consistently significant risk factors for AOM and recurrent AOM. CONCLUSIONS: In the era of PNSP, restricted use of antibiotic chemoprophylaxis for recurrent AOM was not associated with significantly increased rates of new onset AOM episodes or tube placement in the first 24 months of life. Total antibiotic days were also significantly reduced in Cohort 2 during Years 2 and 3.

Acute Disease↗

Abnormal dicentric chromosome with co-amplification of sequences from chromosomes 11 and 19: a novel rearrangement in a patient with myelodysplastic syndrome transforming to acute myeloid leukemia.

A 66-year-old man with a myelodysplastic syndrome transforming to acute myeloid leukemia showed a complex abnormal karyotype on bone marrow aspirate. An unbalanced dicentric translocation with a very long der(11) long arm-dic(11;19)(q25;p13.4)-was present. Fluorescence in situ hybridization studies utilised paints for chromosomes 11 and 19 as well as the locus specific probe MLL, localised to 11q23. The abnormal chromosome 11q contained 6 copies of intact MLL and 6 copies of chromosome 19 (unidentified) sequences. To our knowledge, gene co-amplification of chromosomes 11 and 19 sequences has not been reported before.

Acute Disease↗

The antiosteoporotic efficacy of intravenous pamidronate in men with prostate carcinoma receiving combined androgen blockade: a double blind, randomized, placebo-controlled crossover study.

BACKGROUND: Prostate carcinoma therapy with combined androgen blockade may result in high bone-turnover with significant bone loss. This study was undertaken to evaluate the antiosteoporotic efficacy of intravenous pamidronate in a double blind, randomized, placebo-controlled, crossover study. METHODS: Twenty-one consecutive men with metastatic prostate carcinoma who were receiving combined androgen blockade with a long-acting gonadotropin-releasing hormone agonist (gosarelin acetate) and an androgen antagonist (flutamide or bicalutamide) were evaluated at baseline and at 6 and 12 months after therapy. They were randomly assigned to receive a single intravenous infusion of 500 mL of normal saline solution diluted with either pamidronate (90 mg) or placebo at baseline and with a crossover at 6 months. Lumbar-spine bone-mineral densities (BMDs) were measured by spinal quantitative computed tomography (QCT), femoral neck BMDs were measured by dual-energy X-ray absorptiometry (DXA), and markers of bone turnover were measured by noninvasive methods. Data on 10 men with localized prostate carcinoma who were treated with radiotherapy alone, over the same period, was collected for comparison studies. RESULTS: The mean age of the men was 75.1 years +/- 1.6 years. One man withdrew from the study because of deteriorating health, and two died from metastatic disease within the first 6 months. Combined androgen blockade normalized serum prostate-specific antigen activities (from an initial mean value of 86.2 ng/mL +/- 10.1 ng/mL) and maintained serum free testosterone concentrations in the hypogonadal range (< 2.2 pmol/L) in all men throughout the study. Treatment with pamidronate resulted in a 7.8% +/- 1.5% increase in mean lumbar spine QCT from 79.4 mg/cm(3) (95% confidence interval [CI], 64-94 mg/cm(3)) to 85.6 mg/cm(3) (95% CI, 70-101 mg/cm(3)) (P = 0.0005) and a 2% +/- 0.9% increase in mean total femoral neck DXA from 0.98 g/cm(2) (95% CI, 0.90 -1.05 g/cm(2)) to 1.0 mg/cm(2) (95% CI, 0.91-1.08 g/cm(2)) (P = 0.02). Conversely, treatment with placebo, resulted in a 5.7% +/- 1.6% decrease in mean lumbar spine QCT and a 2.3% +/- 0.7% decrease in mean total femoral neck DXA (P = 0.0001 and P = 0.0007 for the comparison of percentage change between the pamidronate and placebo treatments). After pamidronate therapy, serum bone Gla-protein concentrations decreased by 16.8% +/- 5.9%, and urinary deoxypyridinoline excretion rates decreased by 18.5% +/- 12.8% (P < 0.01 respectively for the comparison between pamidronate and placebo treatment). CONCLUSIONS: This study demonstrated that a single intravenous infusion of pamidronate (90 mg) significantly reduced the high bone turnover and bone loss (for at least 6 mos) in men with prostate carcinoma who had been rendered hypogonadal with combined androgen blockade therapy.

Aged↗

Sirolimus for rescue and primary immunosuppression in transplanted children receiving tacrolimus.

AIMS: The role of sirolimus (SRL) as a rescue agent (n=42) and as a component of primary immunosuppression (n=8) was evaluated in a mixed population of 50 transplanted children receiving tacrolimus (liver: 26, heart: 5, intestinal: 5, liver-intestine: 9, lung: 1, bone marrow: 1, liver-kidney: 1, multivisceral: 1). Rescue indications for tacrolimus (TAC) failure were recurrent acute rejection and acute rejection complicating withdrawal of immunosuppression in posttransplant lymphoproliferative disorder (PTLD). Rescue indications for TAC toxicity were nephrotoxicity, pancreatitis, seizures, hypertrophic cardiomyopathy, and graft-versus-host disease. RESULTS: Mean age at rescue was 11.5 years and mean follow-up was 204 (range 18-800) days. As primary immunosuppression, SRL+TAC prevented early acute rejection in 7/8 children. The indication for rescue resolved in 33/42 children. In children with TAC toxicity, this was associated with decrease in TAC doses by 50%, significant improvements in renal function, and continuing decline in Epstein-Barr virus (EBV) viral load in PTLD patients. Serious adverse events led to discontinuation of SRL in 9/42 rescue patients, 3 of them also experienced acute rejection. Three additional children also experienced acute rejection on SRL therapy (overall incidence 6/50, 12%). Pharmacokinetic analysis in the first week of SRL administration suggested a short half-life (11.8+/-5.5 hr, n=21). CONCLUSIONS: SRL and reduced-dose TAC may achieve adequate immunosuppression without compromising renal function or enhancing EBV viremia significantly.

Acute Disease↗

Cross infection control measures and the treatment of patients at risk of Creutzfeldt Jakob disease in UK general dental practice.

AIMS: To determine the suitability of key infection control measures currently employed in UK dental practice for delivery of dental care to patients at risk of prion diseases. MATERIALS AND METHODS SUBJECTS: Five hundred dental surgeons currently registered with the General Dental Council of the UK. DATA COLLECTION: Structured postal questionnaire. ANALYSIS: Frequencies, cross-tabulations and chi-squared analysis. RESULTS: The valid response rate to the questionnaire was 69%. 33% of practices had no policy on general disinfection and sterilisation procedures. Only 10 of the 327 responding practices (3%) possessed a vacuum autoclave. 49% of dentists reported using the BDA medical history form but less than 25% asked the specific questions recommended by the BDA to identify patients at risk of iatrogenic or familial CJD. However, 63% of practitioners would refer such patients, if identified, to a secondary care facility. Of the 107 practitioners who were prepared to provide dental treatment, 75 (70%) would do so using routine infection control procedures. CONCLUSIONS: Most of the dental practices surveyed were not actively seeking to identify patients at risk of prion diseases. In many cases, recommended procedures for providing safe dental care for such patients were not in place.

Adult↗

Rate measurement of D(0)-->K+pi(-)pi(0) and constraints on D(0) -- D(0) mixing.

We present an observation and time-integrated rate measurement of the decay D(0)-->K(+)pi(-)pi(0) produced in 9 fb(-1) of e(+)e(-) collisions near the Upsilon(4S) resonance. The signal is inconsistent with an upward fluctuation of the background by 4.9 standard deviations. We measured the time-integrated rate of D(0)-->K(+)pi(-)pi(0) normalized to the rate of D(0)-->K(+)pi(-)pi(0) to be 0.0043(+0.0011)(-0.0010) (stat)+/-0.0007 (syst). This decay can be produced by doubly Cabibbo-suppressed decays or by the D(0) evolving into a D(0) through mixing, followed by a Cabibbo-favored decay to K(+)pi(-)pi(0). We also found the CP asymmetry A = (9(+25)(-22))% be consistent with zero.

Journal Article↗

Experimental investigation of the two-photon widths of the chi(c0) and the chi(c2) mesons.

Using 12.7 fb(-1) of data collected with the CLEO detector at CESR, we observed two-photon production of the cc states chi(c0) and chi(c2) in their decay to pi(+)pi(-)pi(+)pi(-). We measured gamma(gammagamma)(chi(c))xB(chi(c)-->pi(+)pi(-)pi(+)pi(-)) to be 75+/-13(stat)+/-8(syst) eV for the chi(c0) and 6.4+/-1.8(stat)+/-0.8(syst) eV for the chi(c2), implying gamma(gammagamma)(chi(c0)) = 3.76+/-0.65(stat)+/-0.41(syst)+/-1.69(br) keV and gamma(gammagamma)(chi(c2)) = 0.53+/-0.15(stat)+/-0.06(syst)+/-0.22(br) keV. Also, cancellation of dominant experimental and theoretical uncertainties permits a precise comparison of gamma(gammagamma)(chi(c0))/gamma(gammagamma)(chi(c2)), evaluated to be 7.4+/-2.4(stat)+/-0.5(syst)+/-0.9(br), with QCD-based predictions.

Journal Article↗

Spectrum of myelopathies in HIV seropositive South African patients.

The authors determined the cause of myelopathies in 33 HIV seropositive individuals in KwaZulu/Natal, South Africa. The main associations were with human T-cell lymphotrophic virus-I, tuberculosis, herpes zoster, and syphilis. A novel association with probable bilharziasis was noted. Only one case of vacuolar myelopathy was identified. Opportunistic infections will probably persist until routine antiretroviral therapy becomes widely available in South Africa.

Adult↗

Cutaneous basal cell carcinomas: distinct host factors are associated with the development of tumors on the trunk and on the head and neck.

BACKGROUND: Patients with basal cell carcinoma (BCC) demonstrate marked variation in clinical phenotype, suggesting the presence of distinct subgroups. Patients with truncal lesions comprise an interesting subgroup, because, although the pathogenesis of these tumors is unclear, there is evidence to suggest that their development is mediated by different mechanisms than the mechanisms that mediate the development of BCC on other sites. The authors now speculate that some patients inherit a predisposition to truncal BCC and develop disproportionately more BCC on this site than other patients. METHODS: The authors studied 100 patients who, at the time of initial presentation, had a truncal BCC lesion and 493 patients who had a lesion on the head and neck. The 493 patients with head and neck lesions included 36 patients who subsequently developed a truncal BCC and 457 patients who do not. RESULTS: Initial presentation with a truncal tumor was associated with significantly more subsequent BCC lesions on this site compared with patients who presented initially with a head and neck lesion. The mean truncal tumor accrual after initial presentation in patients who presented with an initial truncal BCC lesion was 0.13 BCC lesions per year compared with 0.03 BCC lesions per year in patients who presented with an initial head and neck lesion (P < 0.001). Patients with truncal lesions were significantly younger at the time of initial presentation and developed more clusters of BCC lesions (2--10 new tumors at any presentation) compared with patients who did not develop tumors on the trunk. CONCLUSIONS: These data suggest that the development of a truncal BCC is not random but, rather, is associated with a predisposition. In contrast, the accrual of nontruncal BCC lesions was similar in patients with and without initial truncal lesions, suggesting that different mechanisms determine the development of truncal BCC and nontruncal BCC.

Adult↗

Imprinting status of 11p15 genes in Beckwith-Wiedemann syndrome patients with CDKN1C mutations.

Beckwith-Wiedemann syndrome (BWS) is an imprinting disorder characterized by somatic overgrowth, congenital malformations, and predisposition to childhood tumors. Aberrant expression of multiple imprinted genes, including H19, IGF2, KCNQ1OT1, and CDKN1C, has been observed in BWS patients. It has been estimated that mutations in CDKN1C occur in 12-17% of BWS patients. We have screened 10 autosomal dominant pedigrees and 65 sporadic BWS cases by PCR/heteroduplex analysis and DNA sequencing and have identified four mutations, two of which were associated with biallelic IGF2 expression and normal H19 and KCNQ1OT1 imprinting. One patient demonstrated phenotypic expression of paternally transmitted mutation in this maternally expressed gene, a second proband is the child of one of a pair of monozygotic twin females who carry the mutation de novo, and a third patient exhibited unusual skeletal changes more commonly found in other overgrowth syndromes. When considered with other studies published to date, this work reveals the frequency of CDKN1C mutations in BWS to be only 4.9%. This is the first report of an analysis of the imprinting status of genes in the 11p15 region where CDKN1C mutations were associated with loss of IGF2 imprinting and maintenance of H19 and KCNQ1OT1 imprinting.

Amino Acid Sequence↗

Bounds on the CP asymmetry in like-sign dileptons from B(0)B*(0) meson decays.

We have measured the charge asymmetry in like-sign dilepton yields from B(0)B*(0) meson decays using the CLEO detector at the Cornell Electron Storage Ring. We find a(0)(ll) identical with[N(l(+)l(+))-N(l(-)l(-))]/[N(l(+)l(+))+N(l(-)l(-))] = +0.013+/-0.050+/-0.005. We combine this result with a previous, independent measurement and obtain Re(epsilon(B))/(1+ the absolute value of epsilon(B)(2)) = +0.0035+/-0.0103+/-0.0015 (uncertainties are statistical and systematic, respectively) for the CP impurity parameter, epsilon(B).

Journal Article↗

Randomised controlled trial of self management leaflets and booklets for minor illness provided by post.

OBJECTIVE: To assess the effectiveness of providing information by post about managing minor illnesses. DESIGN: Randomised controlled trial. SETTING: Six general practices. PARTICIPANTS: Random sample of 4002 patients from the practice registers. INTERVENTION: Patients were randomised to receive one of three kinds of leaflet or booklet endorsed by their general practitioner: control (surgery access times), booklet, or summary card. MAIN OUTCOME MEASURES: Attendance with the 42 minor illnesses listed in the booklet. Perceived usefulness of leaflets or booklets, confidence in managing illness, and willingness to wait before seeing the doctor. RESULTS: 238 (6%) patients did not receive the intervention as allocated. Of the remaining 3764 patients, 2965 (79%) had notes available for review after one year. Compared with the control group, fewer patients attended commonly with the minor illnesses in the booklet group (>/=2 consultations a year: odds ratio 0.81, 95% confidence interval 0.67 to 0.99) and the summary card group (0.83; 0.72 to 0.96). Among patients who had attended with respiratory tract infections in the past year there was a reduction in those attending in the booklet group (0.81; 0.62 to 1.07) and summary card group (0.67; 0.51 to 0.89) compared with the control group. The incidence of contacts with minor illness fell slightly compared with the previous year in the booklet (incidence ratio 0.97; 0.84 to 1.13) and summary card groups (0.93; 0.80 to 1.07). More patients in the intervention groups felt greater confidence in managing illness (booklet 32%, card 34%, control 12%, P<0.001), but there was no difference in willingness to wait score (all groups mean=32, P=0.67). CONCLUSION: Most patients find information about minor illness provided by post useful, and it helps their confidence in managing illness. Information may reduce the number attending commonly with minor illness, but the effect on overall contacts is likely to be modest. These data suggest that posting detailed information booklets about minor illness to the general population would have a limited effect.

Adult↗

Growth inhibition of Bacteroides fragilis by hemopexin: proteolytic degradation of hemopexin to overcome heme limitation.

The stimulatory effect of heme on growth of Bacteroides fragilis, an anaerobic human pathogen, was strongly inhibited by hemopexin, an avid (Kd<1 pM) heme-binding plasma protein. Both rabbit and human hemopexins were bacteriostatic for a limited period of time, suggesting an adaptation by B. fragilis to heme-limited growth, and that hemopexin-bound heme can eventually be utilized by the bacteria. The inhibitory effect of hemopexin was lost when heme in the medium was replaced by protoporphyrin IX, which is bound less strongly by hemopexin (Kd approximately 1 microM). Protease activity was detected in the culture supernatant of B. fragilis grown in the presence of heme plus hemopexin but not in the presence of free heme, protoporphyrin IX or protoporphyrin IX plus hemopexin, suggesting that the enzyme(s) is induced by heme macrocycle limitation due to the scavenging effect of hemopexin. This protease activity was able to degrade rabbit hemopexin and human hemopexin, as well as human transferrin and ovalbumin, and may be a due to a serine protease since it was inhibited by phenylmethylsulfonyl fluoride (PMSF) but not by EDTA, leupeptin, pepstatin A or aprotinin. Thus, B. fragilis may overcome hemopexin-mediated heme limitation by secreting inducible protease(s), shown here to make protein-bound heme available to the microorganism.

Animals↗

Observation of B --> phiK and B --> phiK*.

We have studied two-body charmless hadronic decays of B mesons into the final states straight phiK and phiK(*). Using 9.7 million B&Bmacr; pairs collected with the CLEO II detector, we observe the decays B- --> phiK- and B0--> phiK(*0) with the following branching fractions: B(B--->phiK-) = (5.5(+2.1)(-1.8)+/-0.6)x10(-6) and B(B0--> phiK(*0)) = (11.5(+4.5+1.8)(-3.7-1.7))x10(-6). We also see evidence for the decays B0-->phiK0 and B---> phiK(*-). However, since the statistical significance is not overwhelming for these modes, we determine upper limits of <12.3x10(-6) and <22.5x10(-6) ( 90% confidence level), respectively.

Journal Article↗