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Biomedical subjects

R King

Publications and source records attributed to R King.

At least 55 records · Page 3Linked to original sources
PubMed2000

Engraftment and survival after unrelated-donor bone marrow transplantation: a report from the national marrow donor program.

We analyzed engraftment of unrelated-donor (URD) bone marrow in 5246 patients who received transplants facilitated by the National Marrow Donor Program between August 1991 and June 1999. Among patients surviving at least 28 days, 4% had primary graft failure (failure to achieve an absolute neutrophil count > 5 x 10(8)/L before death or second stem-cell infusion). Multivariate logistic regression analysis showed that engraftment was associated with marrow matched at HLA-A, HLA-B, and DRB1; higher cell dose; younger recipient; male recipient; and recipient from a non-African American ethnic group. More rapid myeloid engraftment was associated with marrow serologically matched at HLA-A and HLA-B, DRB1 match, higher cell dose (in non-T-cell-depleted cases), younger recipient, recipient seronegativity for cytomegalovirus (CMV), male donor, no methotrexate for graft-versus-host disease prophylaxis, and transplantation done in more recent years. A platelet count higher than 50 x 10(9)/L was achieved by 47% of patients by day 100. Conditional on survival to day 100, survival at 3 years was 61% in those with platelet engraftment at day 30, 58% in those with engraftment between day 30 and day 100, and 33% in those without engraftment at day 100 (P <.0001). Factors favoring platelet engraftment were higher cell dose, DRB1 allele match, recipient seronegativity for CMV, HLA-A and HLA-B serologically matched donor, and male donor. Secondary graft failure occurred in 10% of patients achieving initial engraftment, and 18% of those patients are alive. These data demonstrate that quality of engraftment is an important predictor of survival after URD bone marrow transplantation.

Adolescent↗
PubMed2000

Combinatorial diversification of indinavir: in vivo mixture dosing of an HIV protease inhibitor library.

An efficient combination solution-phase/solid-phase route enabling the diversification of the P1', P2', and P3 subsites of indinavir has been established. The synthetic sequence can facilitate the rapid generation of HIV protease inhibitors possessing more favorable pharmacokinetic properties as well as enhanced potencies. Multiple compound dosing in vivo may also accelerate the identification of potential drug candidates.

Animals↗
PubMed2000

Unrelated donor marrow transplantation for chronic myelogenous leukemia: 9 years' experience of the national marrow donor program.

Over a period of 8.5 years (February 1988 to October 1996), 1423 patients with chronic myelogenous leukemia (CML) underwent unrelated donor (URD) bone marrow transplants (BMTs) facilitated by the National Marrow Donor Program (NMDP) at 85 transplant centers. One hundred thirty-seven evaluable (9.9%) patients failed to engraft, and an additional 83 (6.6%) evaluable patients experienced late graft failure. Grade III/IV acute graft-versus-host disease (GVHD) developed in 33% of patients (95% confidence interval [CI], 30%-36%). The incidence of extensive chronic GVHD was 60% (95% CI, 56%-63%) at 2 years. Only 5.7% of patients (95% CI, 3.6%-7.8%) transplanted in chronic phase developed hematologic relapse at 3 years. Several factors were independently associated with improved disease-free survival (DFS), including transplant in chronic phase, transplant within 1 year of diagnosis, younger recipient age, a cytomegalovirus seronegative recipient, and development of no or mild acute GVHD. The combined effect of these factors on outcome is manifest in a subset (n = 157) of young (less than 35 years), chronic phase patients transplanted within 1 year of diagnosis using HLA-matched donors who had 63% (95% CI, 53%-73%) DFS at 3 years. URD BMT therapy for CML is both feasible and effective with more frequent and more rapid identification of suitable donors. Early URD transplant during chronic phase yields good results and should be considered in CML patients otherwise eligible for transplant but without a suitable related donor.

Age Factors↗
PubMed2000

Characterization of peptidyl boronic acid inhibitors of mammalian 20 S and 26 S proteasomes and their inhibition of proteasomes in cultured cells.

Proteasomes are large multisubunit proteinases which have several distinct catalytic sites. In this study a series of di- and tri-peptidyl boronic acids have been tested on the chymotrypsin-like activity of purified mammalian 20 S and 26 S proteasomes assayed with succinyl-Leu-Leu-Val-Tyr-amidomethylcoumarin (suc-Leu-Leu-Val-Tyr-AMC) as substrate. The inhibition of 20 S proteasomes is competitive but only slowly reversible. The K(i) values for the best inhibitors were in the range 10-100 nM with suc-Leu-Leu-Val-Tyr-AMC as substrate, but the compounds tested were much less effective on other proteasome activities measured with other substrates. Free boronic acid inhibitors exhibited equivalent potency to their pinacol esters. Both benzoyl (Bz)-Phe-boroLeu and benzyloxycarbonyl (Cbz)-Leu-Leu-boroLeu pinacol ester inhibited 20 S and 26 S proteasomes with non-ideal behaviour, differences in inhibition of the two forms of proteasomes becoming apparent at high inhibitor concentrations (above 3xK(i)). Both of these compounds were also potent inhibitors of 20 S and 26 S proteasomes in cultured cells. However, gel filtration of cell extracts prepared from cells treated with radiolabelled phenacetyl-Leu-Leu-boroLeu showed that only 20 S proteasomes were strongly labelled, demonstrating differences in the characteristics of inhibition of 20 S and 26 S proteasomes. The usefulness of peptidyl boronic acid inhibitors for investigations of proteasome-mediated protein degradation was confirmed by the observation that Bz-Phe-boroLeu and Cbz-Leu-Leu-boroLeu pinacol ester inhibited NFkappaB activation with IC(50) values comparable to their K(i) values for purified proteasomes. The latter result supports the view that the chymotrypsin-like activity of proteasomes assayed with suc-Leu-Leu-Val-Tyr-AMC is a critical one for protein degradation in cells.

Animals↗
PubMed2000

Treatment of relapsed leukemia after unrelated donor marrow transplantation with unrelated donor leukocyte infusions.

The efficacy and toxicity of donor leukocyte infusions (DLI) after unrelated donor bone marrow transplantation (BMT) is largely unknown. We identified 58 recipients of unrelated DLI (UDLI) for the treatment of relapsed disease from the National Marrow Donor Program database. A retrospective analysis was performed to determine response, toxicity, and survival after UDLI and to identify factors associated with successful therapy. UDLI was administered for relapsed chronic myelogenous leukemia (CML) (n = 25), acute myelogenous leukemia (AML) (n = 23), acute lymphoblastic leukemia (ALL) (n = 7), and other diseases (n = 3). Eight patients were in complete remission (CR) before UDLI, and 50 were evaluable for response. Forty-two percent (95% confidence interval [CI], 28%-56%) achieved CR, including 11 of 24 (46%; 95% CI, 26%-66%) with CML, 8 of 19 (42%; 95% CI, 20%-64%) with AML, and 2 of 4 (50%; 95% CI, 1%-99%) with ALL. The estimated probability of disease-free survival (DFS) at 1 year after CR was 65% (95% CI, 50%-79%) for CML, 23% (95% CI, 9%-38%) for AML, and 30% (95% CI, 6%-54%) for ALL. Acute graft-versus-host disease (GVHD) complicated UDLI in 37% of patients (grade II-IV, 25%). A total of 13 of 32 evaluable patients (41%) developed chronic GVHD. There was no association between cell dose administered and either response or toxicity. In a multivariable analysis, only a longer interval from BMT to relapse and BMT to UDLI was associated with improved survival and DFS, respectively. UDLI is an acceptable alternative to other treatment options for relapse after unrelated donor BMT. (Blood. 2000;95:1214-1221)

Analysis of Variance↗
PubMed2000

Preliminary findings of antistreptococcal antibody titers and basal ganglia volumes in tic, obsessive-compulsive, and attention deficit/hyperactivity disorders.

BACKGROUND: Previous studies have provided preliminary serological evidence supporting the theory that symptoms of tic disorders or obsessive-compulsive disorder (OCD) may be sequelae of prior streptococcal infection. It is unclear, however, whether previously reported associations with streptococcal infection were obscured by the presence of diagnostic comorbidities. It is also unknown whether streptococcal infection is associated in vivo with anatomical alterations of the brain structures that have been implicated in the pathophysiology of these disorders. METHODS: Antistreptococcal antibody titers were measured in 105 people diagnosed as having CTD, OCD, or attention-deficit/hyperactivity disorder (ADHD) and in 37 community controls without a disorder. Subjects were unselected with regard to their history of streptococcal exposure. Basal ganglia volumes were measured in 113 of these subjects (79 patients and 34 controls). RESULTS: A DSM-IV diagnosis of ADHD was associated significantly with titers of 2 distinct antistreptococcal antibodies, antistreptolysin O and anti-deoxyribonuclease B. These associations remained significant after controlling for the effects of CTD and OCD comorbidity. No significant association was seen between antibody titers and a diagnosis of either CTD or OCD. When basal ganglia volumes were included in these analyses, the relationships between antibody titers and basal ganglia volumes were significantly different in OCD and ADHD subjects compared with other diagnostic groups. Higher antibody titers in these subjects were associated with larger volumes of the putamen and globus pallidus nuclei. CONCLUSIONS: These findings suggest that the prior reports of an association between antistreptococcal antibodies and either CTD or OCD may have been confounded by the presence of ADHD. They also support the hypothesis that in susceptible persons who have ADHD or OCD, chronic or recurrent streptococcal infections are associated with structural alterations in basal ganglia nuclei.

Adult↗
PubMed2000

Mechanistic investigation of ionization suppression in electrospray ionization.

We show results from experiments designed to determine the relative importance of gas phase processes and solution phase processes into ionization suppression observed in biological sample extracts. The data indicate that gas phase reactions leading to the loss of net charge on the analyte is not likely to be the most important process involved in ionization suppression. The results point to changes in the droplet solution properties caused by the presence of nonvolatile solutes as the main cause of ionization suppression in electrospray ionization of biological extracts.

Blood Proteins↗
PubMed2000

Giant-sized condyloma of the breast with focal acantholytic changes.

BACKGROUND: A healthy 26-year-old pregnant woman presented with a 6.0-cm exophytic mass in her left inframammary fold. The lesion was surgically excised. METHODS: Histopathologic sections of the skin lesion were reviewed in hematoxylin and eosin-stained slides. Additional sections were studied by an in situ hybridization method for human papillomavirus DNA (HPV) types 6 and 11. RESULTS: The histopathologic examination demonstrated a benign exophytic, verrucous and papillary epidermal proliferation with features of condyloma acuminatum. Reactivity to HPV DNA types 6 and 11 was demonstrated by in situ hybridization method. The epidermis adjacent to, and focally within, the neoplasm showed multiple areas of suprabasilar and intraepidermal acantholysis without dyskeratosis. CONCLUSIONS: Condylomas related to HPV 6 and 11 may be found in extragenital locations including conjunctiva, oral and nasal mucosa. To our knowledge, however, the extragenital condylomas described in the literature have not included the giant-sized variant. We describe an example of a benign, giant-sized condyloma acuminatum of the breast with nearby acantholytic alterations similar to Hailey-Hailey disease.

Adult↗
PubMed2000

Performance of the radiometer OSM3 and ABL505 blood gas analysers for determination of sodium, potassium and haemoglobin concentrations.

We have compared results obtained from two widely used ward-based blood gas analysers, the Radiometer OSM3 and ABL505, with standard laboratory analysers, for haemoglobin, sodium and potassium measurement in critically ill adult patients. During the study, paired samples for analysis were obtained from 81 patients for haemoglobin, 115 patients for sodium and 95 patients for potassium. There was good agreement between the ward and the laboratory analysers in terms of the mean results for each test. However, the limits of agreement for the ward-based analysers were wide, suggesting that their results should be used with caution.

Adult↗
PubMed2000

Adverse behavioral and sexual factors in chronic vulvar disease.

OBJECTIVE: We investigated the prevalence of adverse sexual, personal hygiene, and self-treatment behavior among women with chronic benign vulvar and vaginal disorders. STUDY DESIGN: This study was carried out by means of a scientific clinical audit producing actuarial data by way of a semistructured questionnaire. Subjects consisted of a sample of 530 cases treated at a specialist clinic for vulvar diseases. In addition to clinical and laboratory investigations, the patients were interviewed by the clinic's psychologist, who used a structured interview schedule developed specifically for the study. Descriptive analysis and analysis of variance were used to investigate data. RESULTS: Most patients remained sexually active in spite of arousal failure and discomfort and engaged in unlubricated and often painful sexual intercourse. Most women engaged in potentially harmful genital hygiene and self-treatment behavior. Adverse self-treatment practices but not adverse genital hygiene practices were associated with greater symptom duration. CONCLUSIONS: Adverse practices should be addressed during the management of cases of chronic vulvar disease.

Adult↗
PubMed2000

Use of nitric oxide for decompensated right ventricular failure and circulatory shock after cardiac arrest.

We describe a case of peri-operative cardiac arrest, severe right ventricular failure and pulmonary hypertension in a 60-yr-old woman with interstitial pulmonary fibrosis. Inhaled nitric oxide therapy rapidly improved arterial oxygenation and haemodynamic variables, allowing recovery and weaning from mechanical ventilation. Subsequently, the patient was discharged from the cardiac intensive care unit.

Anesthesia, General↗
PubMed2000

The impact of caseload on the personal efficacy of mental health case managers.

OBJECTIVE: The relationship between caseload size and self-perceived clinical effectiveness of mental health case managers was explored. METHODS: A 17-item instrument developed for the study, the Case Manager Personal Efficacy Scale (CMPES), was completed by 300 community mental health case managers in Australia. Efficacy scores were examined in relation to caseload size and to respondents' scores on the General Health Questionnaire. RESULTS: The CMPES was sensitive to changes in caseload size. Case managers with larger caseloads reported lower performance in a range of core role activities. Larger caseload had a weak but significant negative association with general well-being as measured by the General Health Questionnaire. CONCLUSIONS: Caseload size had a significant impact on the self-perceived role performance of mental health case managers. The CMPES is a reliable measure of case manager personal efficacy that is sensitive to variation in work context.

Adult↗
PubMed2000

Rapid cycling bipolar disorder in individuals with developmental disabilities.

The assessment and treatment of the rapid-cycling variant of bipolar disorder in individuals with developmental disabilities is challenging. Outcomes are optimized by a long-term commitment to the establishment of objective monitoring systems by interdisciplinary teams. In this retrospective case series, we contrast the phenomenology, clinical outcomes, treatment responses, and clinical characteristics of 26 individuals with bipolar disorder and developmental disabilities, 12 with nonrapid cycling courses and 14 with rapid cycling courses. Similarities and differences are highlighted both within these two groups and in reference to published findings for individuals without disabilities.

Adolescent↗