Biomedical subjects

D C Young

Publications and source records attributed to D C Young.

At least 19 recordsLinked to original sources

PubMed2001

Obesity: assessment and management in primary care.

Obesity is a complex, multifactorial condition in which excess body fat may put a person at health risk. National data indicate that the prevalence of obesity in the United States is increasing in children and adults. Reversing these trends requires changes in individual behavior and the elimination of societal barriers to healthy lifestyle choices. Basic treatment of overweight and obese patients requires a comprehensive approach involving diet and nutrition, regular physical activity, and behavioral change, with an emphasis on long-term weight management rather than short-term extreme weight reduction. Physicians and other health professionals have an important role in promoting preventive measures and encouraging positive lifestyle behaviors, as well as identifying and treating obesity-related comorbidities. Health professionals also have a role in counseling patients about safe and effective weight loss and weight maintenance programs. Recent evidence-based guidelines from the National Heart, Lung, and Blood Institute, as well as recommendations from the American Academy of Pediatrics, American Association of Clinical Endocrinologists/American College of Endocrinology, American Obesity Association, U.S. Clinical Preventive Services Task Force, Institute of Medicine, and World Health Organization can be consulted for information and guidance on the identification and management of overweight and obese patients.

Adolescent↗

PubMed2001

Methods to improve efficacy of intravesical mitomycin C: results of a randomized phase III trial.

BACKGROUND: Intravesical chemotherapy (i.e., placement of the drug directly in the bladder) with mitomycin C is beneficial for patients with superficial bladder cancer who are at high risk of recurrence, but standard therapy is empirically based and patient response rates have been variable, in part because of inadequate drug delivery. We carried out a prospective, two-arm, randomized, multi-institutional phase III trial to test whether enhancing the drug's concentration in urine would improve its efficacy. METHODS: Patients with histologically proven transitional cell carcinoma and at high risk for recurrence were eligible for the trial. Patients in the optimized-treatment arm (n = 119) received a 40-mg dose of mitomycin C, pharmacokinetic manipulations to increase drug concentration by decreasing urine volume, and urine alkalinization to stabilize the drug. Patients in the standard-treatment arm (n = 111) received a 20-mg dose without pharmacokinetic manipulations or urine alkalinization. Both treatments were given weekly for 6 weeks. Primary endpoints were recurrence and time to recurrence. Treatment outcome was examined by use of Kaplan-Meier analysis with log-rank tests. Statistical tests were two-sided. RESULTS: Patients in the two arms did not differ in demographics or history of intravesical therapy. Dysuria occurred more frequently in the optimized arm but did not lead to more frequent treatment termination. In an intent-to-treat analysis, patients in the optimized arm showed a longer median time to recurrence (29.1 months; 95% confidence interval [CI] = 14.0 to 44.2 months) and a greater recurrence-free fraction (41.0%; 95% CI = 30.9% to 51.1%) at 5 years than patients in the standard arm (11.8 months; 95% CI = 7.2 to 16.4 months) and 24.6% (95% CI = 14.9% to 34.3%) (P =.005, log-rank test for time to recurrence). Improvements were found in all risk groups defined by tumor stage, grade, focality, and recurrence. CONCLUSIONS: This study identified a pharmacologically optimized intravesical mitomycin C treatment with statistically significantly enhanced efficacy.

Administration, Intravesical↗

PubMed2001

Excessive uterine activity accompanying induced labor.

OBJECTIVE: To estimate the incidence and timing of excessive uterine activity accompanying induction of labor with misoprostol using different routes (oral or vaginal) and forms (intact tablet or crushed) and to compare these with dinoprostone gel, oxytocin, and spontaneous labor. METHODS: This retrospective cohort study included 519 women at term who had labor induced and 86 women at term in spontaneous labor. Induction agents included misoprostol, dinoprostone, or oxytocin. Fetal heart rate and uterine activity tracings were analyzed independently by three maternal-fetal medicine physicians. The diagnosis of tachysystole or hyperstimulation required the agreement of two or more reviewers. RESULTS: The incidence of tachysystole was highest with misoprostol administered by vaginal tablet (misoprostol vaginal tablet 50 microg every 4 hours, 48.6%; vaginal tablet crushed 50 microg and suspended in hydroxyethyl gel every 4 hours, 30.7%, P =.009; oral tablet 50 microg every 4 hours, 22.2%, P =.001; oral tablet crushed 50 microg every 4 hours, 15.5%, P <.001; dinoprostone gel, 33.0%, P =.022; intravenous oxytocin, 30.2%, P =.027; and spontaneous onset of labor, 23.3%, P <.001). Hyperstimulation occurred more often with dinoprostone gel (16.5%) than with other forms of induction or spontaneous labor. Hyperstimulation occurred significantly more often with vaginal misoprostol crushed tablet (7.9%) and vaginal misoprostol intact tablet (7.6%) than with crushed oral misoprostol (1.0%) (P =.016 and.018, respectively). There was a shorter time to tachysystole with increasing doses of vaginal misoprostol tablet (P =.01). CONCLUSION: The incidence of tachysystole and hyperstimulation, and time to tachysystole, varied depending on the route and form of misoprostol given.

Administration, Intravaginal↗

PubMed2001

Transvaginal ultrasound and digital examination in predicting successful labor induction.

OBJECTIVE: To compare transvaginal ultrasound and digital cervical examination in predicting successful induction in post-term pregnancy. METHODS: Transvaginal ultrasound and digital vaginal examinations were performed on 122 women at 41 or more weeks' gestation, immediately before labor induction. Ultrasound assessments of cervical length, dilatation, and presence of funneling were compared with the components of the Bishop score. The primary outcome was the rate of vaginal delivery. Secondary outcomes assessed included the rates of active labor in 12 hours, vaginal delivery in 12 and 24 hours, mean duration of latent phase, and induction to vaginal delivery interval. Linear and multiple logistic regression models were generated to identify factors independently associated with successful induction. RESULTS: No ultrasound characteristic predicted primary or secondary outcomes. Bishop score (odds ratio [OR] 2.98, 95% confidence interval [CI] 1.71, 5.20), cervical position (OR 4.35, 95% CI 1.41, 12.50), and maternal age (OR 1.15, 95% CI 1.01, 1.30) independently predicted vaginal delivery. Maternal weight (OR 0.96, 95% CI 0.94, 0.98), cervical dilatation (OR 6.08, 95% CI 1.70, 21.68), and effacement (OR 2.34, 95% CI 1.16, 4.73) independently predicted active labor in 12 hours. Independent predictors of vaginal delivery in 12 hours were induction method (P <.001), cervical dilatation (OR 11.16, 95% CI 3.17, 39.29), gravidity (OR 2.06, 95% CI 1.13, 3.77), and maternal weight (OR 0.96, 95% CI 0.93, 0.99). Cervical effacement (OR 2.70, 95% CI 1.59, 4.57) and parity (OR 7.10, 95% CI 2.22, 22.72) independently predicted vaginal delivery in 24 hours. Maternal weight, cervical position, and cervical dilatation were independently associated with latent phase labor duration. Factors independently associated with length of induction to delivery interval were parity, cervical effacement, and maternal weight. CONCLUSION: Transvaginal ultrasound does not predict successful labor induction in post-term pregnancy as well as digital cervical examination.

Adult↗

PubMed2001

Suppression of polyclonal immunoglobulin production by M-proteins shows isotype specificity.

Monoclonal gammopathies are B cell neoplasms that are characterized by the presence of monoclonal immunoglobulins (M-proteins) in the serum. By an unknown mechanism, the normal polyclonal immunoglobulin levels are frequently reduced in sera of these patients. To assess the role of M-protein isotype in this effect, we used serum protein electrophoresis to quantitate monoclonal and polyclonal immunoglobulins in patients and we used serum immunofixation electrophoresis to determine their M-protein isotype. When divided into populations of 30 patients with IgG M-proteins (mean 2.5 g/dl) and 19 patients with IgM or IgA M-proteins (mean 2.6 g/dl), the mean polyclonal immunoglobulin level was significantly lower in the IgG M-protein population (0.4 g/dl) than the IgM/IgA population (0.8 g/dl). Patients with IgG M-proteins also had significantly lower polyclonal immunoglobulin levels when compared separately with the patients with either IgA or IgM paraproteins. Since the polyclonal immunoglobulin fraction is comprised mostly of IgG, these results give the first direct indication that IgG M-proteins have a greater suppressive effect on polyclonal IgG levels than do M-proteins of other isotypes. These findings suggest that an isotype-specific feedback mechanism could be involved in the normal regulation of serum IgG levels.

Antibody Specificity↗

PubMed2000

CD1c-mediated T-cell recognition of isoprenoid glycolipids in Mycobacterium tuberculosis infection.

The discovery of the CD1 antigen presentation pathway has expanded the spectrum of T-cell antigens to include lipids, but the range of natural lipid antigens and functions of CD1-restricted T cells in vivo remain poorly understood. Here we show that the T-cell antigen receptor and the CD1c protein mediate recognition of an evolutionarily conserved family of isoprenoid glycolipids whose members include essential components of protein glycosylation and cell-wall synthesis pathways. A CD1c-restricted, mycobacteria-specific T-cell line recognized two previously unknown mycobacterial hexosyl-1-phosphoisoprenoids and structurally related mannosyl-beta1-phosphodolichols. Responses to mannosyl-beta1-phosphodolichols were common among CD1c-restricted T-cell lines and peripheral blood T lymphocytes of human subjects recently infected with M. tuberculosis, but were not seen in naive control subjects. These results define a new class of broadly distributed lipid antigens presented by the CD1 system during infection in vivo and suggest an immune mechanism for recognition of senescent or transformed cells that are known to have altered dolichol lipids.

Adult↗

PubMed2000

Actinonin, a naturally occurring antibacterial agent, is a potent deformylase inhibitor.

Peptide deformylase (PDF) is essential in prokaryotes and absent in mammalian cells, thus making it an attractive target for the discovery of novel antibiotics. We have identified actinonin, a naturally occurring antibacterial agent, as a potent PDF inhibitor. The dissociation constant for this compound was 0.3 x 10(-)(9) M against Ni-PDF from Escherichia coli; the PDF from Staphylococcus aureus gave a similar value. Microbiological evaluation revealed that actinonin is a bacteriostatic agent with activity against Gram-positive and fastidious Gram-negative microorganisms. The PDF gene, def, was placed under control of P(BAD) in E. coli tolC, permitting regulation of PDF expression levels in the cell by varying the external arabinose concentration. The susceptibility of this strain to actinonin increases with decreased levels of PDF expression, indicating that actinonin inhibits bacterial growth by targeting this enzyme. Actinonin provides an excellent starting point from which to derive a more potent PDF inhibitor that has a broader spectrum of antibacterial activity.

Amidohydrolases↗

PubMed2000

Report of the Council on Scientific Affairs. Biohazardous waste management: what the physician needs to know. American Medical Association.

Sources of biohazardous waste include not only large hospitals and laboratories, but also physicians' offices, dental offices, clinics, research facilities, surgery centers, veterinary offices, funeral homes, and a growing number of settings where home health care is delivered. State and local municipality definitions and regulations on biohazardous waste vary widely. Most regulations exempt home health care settings, but include physicians' offices. Although the infectious public health risk posed by medical waste is exceedingly low, this fact is not well understood by the general public. Physicians should develop biohazardous waste management programs that fulfill their county, state, and municipal regulations and that consider the difference between health risks to employees and risks to the general public. Physicians can considerably reduce the amount and costs of biohazardous waste disposal by proper identification and segregation of waste in a manner that meets their state's criteria. Using products that can be recycled may reduce the amount and costs of disposal of biohazardous waste. Processing costs also may be reduced by cooperative arrangements among medical groups or health care facilities to negotiate group disposal rates with vendors.

American Medical Association↗

PubMed2000

Hypothyroidism after treatment for nonthyroid head and neck cancer.

OBJECTIVES: To determine the incidence of posttreatment hypothyroidism in patients treated with surgery with or without radiotherapy for advanced-stage nonthyroid head and neck cancer and to make recommendations for its detection. DESIGN: A prospective study to assess the incidence and time frame of occurrence of hypothyroidism in patients by primary tumor site and treatment modality. Thyroid function tests were performed preoperatively, at the first postoperative visit, and then approximately every 6 months. Patients were followed up for up to 3 years. SETTING: Arthur G. James Cancer Hospital and Research Institute, Columbus, Ohio. PATIENTS: A total of 251 patients with nonthyroid head and neck cancer were originally enrolled; 198 patients with evaluable data were studied to determine the incidence of posttreatment hypothyroidism. Approximately 80% of the patients had advanced stage (III or IV) or recurrent cancer. RESULTS: The overall incidence of posttreatment hypothyroidism was 15% in 198 patients followed up for a mean of approximately 12 months. Hypothyroidism developed in 12% of patients treated with nonlaryngeal surgery and radiotherapy. The group undergoing total laryngectomy (with thyroid lobectomy) and radiotherapy had a 61% incidence of hypothyroidism. The average time to detection of hypothyroidism was 8.2 months. CONCLUSIONS: Approximately 15% of patients treated for advanced head and neck cancer with surgery and radiotherapy will develop hypothyroidism. Those treated with total laryngectomy and radiotherapy are at greatest risk.

Adult↗

PubMed2000

Variation in axillary node dissection influences the degree of nodal involvement in breast cancer patients.

BACKGROUND AND OBJECTIVES: The number of positive axillary lymph nodes predicts prognosis and is often important in determining adjuvant chemotherapy in breast cancer patients. This study was undertaken to determine if differences in the extent of axillary node dissection would alter the number of reported positive nodes. METHODS: The study population consisted of 302 patients with invasive breast cancer who underwent complete (level I/II/III) axillary lymph node dissection. Assuming that all patients had undergone a level I/II dissection, it was determined how frequently a patient's nodal category (0, 1-3, 4-9, >10 positive nodes) would have been altered if a level I or level I/II/III dissection were performed. RESULTS: Assuming that all 302 patients had undergone a level I/II dissection, performing only level I dissection would have resulted in a change in nodal category in 15.9% of all patients and 36.1% of patients with positive nodes. The corresponding changes for a level I/II/III dissection would have been 4.3% and 9.5%, respectively. CONCLUSIONS: Variations in the level of axillary node dissection for breast cancer can result in significant changes in the number of positive axillary nodes. This can potentially bias adjuvant chemotherapy recommendations if treatment decisions are based on this prognostic factor.

Axilla↗

PubMed2000

Comparison of Abbott LCx Chlamydia trachomatis assay with Gen-Probe PACE2 and culture.

In this study the LCx assay (a nucleic acid amplification assay) for Chlamydia trachomatis in endocervical samples was compared with the Gen-Probe PACE2 assay (a nucleic acid probe assay) for endocervical samples, and with endocervical culture. In addition, the efficacy of the LCx assay was determined for midstream clean-catch urine samples because it is often necessary to obtain such a sample for routine urine culture and it is simpler to collect only a single sample without also collecting a first-void urine for LCx. Endocervical specimens from 205 patients were tested for C. trachomatis via LCx and PACE2. Of these patients, 203 were tested by culture. Midstream clean-catch urine samples from 75 of these patients were tested by LCx. The sensitivities and specificities for these assays, after discrepant analysis, were 100 and 98.9% for LCx of endocervical samples, 52.4 and 100% for PACE2; and 71.4 and 100% for culture. The sensitivity/specificity of LCx for midstream clean-catch urines was 66.7/98.5%. The apparent prevalence of C. trachomatis in our population was 10.2%. These data indicate that among the methods tested, LCx of endocervical samples had the highest sensitivity for C. trachomatis in this population. The sensitivity of the urine LCx assay using midstream clean-catch collected urines was considerably less than that reported in other studies that used first-void urines but was higher than that of PACE2.

Adolescent↗

PubMed2000

Acardiac twin pregnancy with neonatal resolution of donor twin cardiomyopathy.

BACKGROUND: Twin reverse arterial perfusion, as with acardiac fetuses, is a rare complication of multifetal pregnancy. Prognosis of the donor twin is guarded because of the high risk of cardiac failure, polyhydramnios, and preterm delivery. CASE: A 40-year-old woman, gravida 4, para 3, was diagnosed at 19 weeks' gestation with a twin pregnancy complicated by an acardiac, acephalic fetus. Serial amniocenteses were done to decompress the hydramnios between 27 and 33 weeks. Ultrasonography showed ventricular septal hypertrophy in the donor twin at 27 weeks, and cesarean delivery was done at 33 weeks. The neonatal course was complicated by hypertrophic cardiomyopathy, which resolved without sequelae by 1 year of age. CONCLUSION: Antenatal sonographic monitoring of interventricular septal thickness can be a useful marker to predict neonatal cardiac sequelae.

Adult↗

PubMed2000

Autotransplantation following busulfan, etoposide and cyclophosphamide in patients with non-Hodgkin's lymphoma.

The purpose of the study was to determine the toxicities and effectiveness of a novel preparative regimen of busulfan (Bu) 14 mg/kg, etoposide 50 or 60 mg/kg, and cyclophosphamide (Cy) 120 mg/kg in non-Hodgkin's lymphoma (NHL) and to analyze results using doses based on different body weight parameters and the two different etoposide doses. Three hundred and eighty-two patients aged 16 to 72 underwent first autologous transplantation with mobilized peripheral blood progenitor cells between August 1992 and December 1998 at either of two transplant centers. Mucositis was the most common toxicity. Hepatic toxicity was the most common life-threatening toxicity; severe hepatic VOD occurred in 11 patients (2.9%). Ten patients (2.6%) died from treatment-related toxicity. The 3-year progression-free survival (PFS) for the entire group was 46.9% (95% CI, 40.5-53.3%). Elevated LDH, resistance to chemotherapy, and intermediate/aggressive histology were significant adverse prognostic factors. For patients in sensitive first relapse PFS was 47.0% (95% CI, 37-57%). Neither etoposide dose nor body weight parameter utilized significantly affected outcome. In conclusion, the novel preparative regimen of Bu, etoposide and Cy results in a low incidence of treatment-related mortality and is effective in the treatment of patients with NHL. Bone Marrow Transplantation (2000) 25, 1243-1248.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

The influence of early transplantation, age, GVHD prevention regimen, and other factors on outcome of allogeneic transplantation for CML following BuCy.

Results in 164 patients who underwent allogeneic marrow transplantation following busulfan and cyclophosphamide over a 15 year period were analyzed. Age (median 37, range 14-66 years) did not significantly affect the incidence of graft-versus-host disease (GVHD), but patients who received methotrexate with cyclosporine had a significantly lower incidence (P = 0.002) of chronic GVHD compared to those who received methylprednisolone with cyclosporine. Hepatic veno-occlusive disease (VOD) occurred less frequently in chronic phase patients (P = 0.002) and in those transplanted shortly after diagnosis (P = 0.001). Five year leukemia-free survival (LFS) for the entire group was 49% (95% CI 41-57%). For 102 patients who underwent transplantation in chronic phase, results were significantly improved by transplantation at a short interval following diagnosis, particularly within 3 months (P = 0.01), by the use of methotrexate and not corticosteroids for GVHD prevention (P = 0.03), and by use of HLA-identical sibling donors (P = 0.01). Age was not a significant adverse prognostic factor and transplantation was successfully performed in individuals up to age 66. Allogeneic transplantation in CML, including older patients and those with unrelated donors, can be most safely and effectively performed shortly after diagnosis.

Adolescent↗

PubMed2000

Quantification of the learning curve for percutaneous dilatational tracheotomy.

OBJECTIVES/HYPOTHESIS: Although numerous investigators have reported a bedside percutaneous dilatational tracheotomy (PDT) complication incidence similar to that of standard operative tracheostomy, others have proposed a "learning curve" for PDT resulting in increased complications early in individual or institutional experience with this procedure. The objective of this investigation is to characterize and quantify the proposed learning curve for PDT. STUDY DESIGN: Prospective analysis of complication incidence for the first 100 PDT procedures performed in a local community hospital Department of General Surgery. METHODS: Demographic data, patient disease variables, and patient anatomic features, as well as perioperative, postoperative, and late complications, were recorded prospectively. Patients were divided into sequential cohorts of 20 and were evaluated for complications at regular intervals. RESULTS: Perioperative and late complication incidence was significantly higher in the first 20 patients who underwent PDT. However, postoperative complication incidence did not significantly vary with operator or institutional experience. In addition, patients with suboptimal anatomy were found to have a significantly increased complication incidence, independent of operator and institutional experience. CONCLUSIONS: Percutaneous dilational tracheotomy has an identifiable learning curve that is most prominent in the first 20 patients treated. Early experience with PDT should be obtained under controlled circumstances, ideally the operating suite. Although most complications occur during acquisition of early experience with PDT, certain life-threatening complications such as tube dislodgment or inability to complete procedure may occur even after extensive experience is obtained. Bedside PDT has an acceptable complication incidence, but any surgeon employing this technique must be prepared to perform immediate standard open tracheotomy to minimize potentially lethal complications of this elective procedure.

Adolescent↗

PubMed2000

Peptide deformylase in Staphylococcus aureus: resistance to inhibition is mediated by mutations in the formyltransferase gene.

Peptide deformylase, a bacterial enzyme, represents a novel target for antibiotic discovery. Two deformylase homologs, defA and defB, were identified in Staphylococcus aureus. The defA homolog, located upstream of the transformylase gene, was identified by genomic analysis and was cloned from chromosomal DNA by PCR. A distinct homolog, defB, was cloned from an S. aureus genomic library by complementation of the arabinose-dependent phenotype of a P(BAD)-def Escherichia coli strain grown under arabinose-limiting conditions. Overexpression in E. coli of defB, but not defA, correlated to increased deformylase activity and decreased susceptibility to actinonin, a deformylase-specific inhibitor. The defB gene could not be disrupted in wild-type S. aureus, suggesting that this gene, which encodes a functional deformylase, is essential. In contrast, the defA gene could be inactivated; the function of this gene is unknown. Actinonin-resistant mutants grew slowly in vitro and did not show cross-resistance to other classes of antibiotics. When compared to the parent, an actinonin-resistant strain produced an attenuated infection in a murine abscess model, indicating that this strain also has a growth disadvantage in vivo. Sequence analysis of the actinonin-resistant mutants revealed that each harbors a loss-of-function mutation in the fmt gene. Susceptibility to actinonin was restored when the wild-type fmt gene was introduced into these mutant strains. An S. aureus Deltafmt strain was also resistant to actinonin, suggesting that a functional deformylase activity is not required in a strain that lacks formyltransferase activity. Accordingly, the defB gene could be disrupted in an fmt mutant.

Amidohydrolases↗

PubMed2000

Adhesive capsulitis of the shoulder in male cardiac surgery patients.

Two hundred fourteen consecutive male cardiac surgery patients were retrospectively evaluated for the incidence of adhesive capsulitis of the shoulder and were assessed for risk factors. Only male patients were included, as the study took place at a Veteran's hospital. Patients who had no shoulder problems prior to cardiac surgery and were experiencing shoulder pain or stiffness postoperatively underwent history, physical examination, and radiographic studies. Thirty-five patients who had shoulder complaints were identified and evaluated. A 3.3% incidence (seven patients) of adhesive capsulitis of the shoulder in a male post-cardiac surgery population was established.

Age Distribution↗

PubMed1999

Restriction landmark genome scanning for aberrant methylation in primary refractory and relapsed acute myeloid leukemia; involvement of the WIT-1 gene.

There is substantial evidence to suggest that aberrant DNA methylation in the regulatory regions of expressed genes may play a role in hematologic malignancy. In the current report, the Restriction Landmark Genomic Scanning (RLGS) method was used to detect aberrant DNA methylation (M) in acute myeloid leukemia (AML). RLGS-M profiles were initially performed using DNA from diagnostic, remission, and relapse samples from a patient with AML. Rp18, one of the eight spots found that was absent in the relapse sample, was cloned. Sequence analysis showed that the spot represented a portion of the WIT-1 gene on human chromosome 11p13. Rp18 was missing in the relapse sample due to a distinct DNA methylation pattern of the WIT-1 gene. Twenty-seven AML patients that entered CR after therapy (i.e., chemosensitive) were studied and only 10 (37%) of the diagnostic bone marrow (BM) samples showed methylation of WIT-1. However, seven of eight (87.5%) diagnostic BM samples from primary refractory AML (chemosensitive) showed methylation of WIT-1. The incidence of WIT-1 methylation in primary refractory AML was significantly higher than that noted in chemosensitive AML (P=0.018). Together, these results indicate that RLGS-M can be used to find novel epigenetic alterations in human cancer that are undetectable by standard methods. In addition, these results underline the potential importance of WIT-1 methylation in chemoresistant AML.

Acute Disease↗