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Biomedical subjects

D Hendricks

Publications and source records attributed to D Hendricks.

13 recordsLinked to original sources
PubMed2006

Accurate model predicting sustained response at week 4 of therapy with pegylated interferon with ribavirin in patients with chronic hepatitis C.

Current models used to predict response to peginterferon plus ribavirin treatment, based on viral decline during the first 12 weeks of therapy, have focused on creating an early stopping rule to avoid unnecessary prolongation of therapy. We developed a multivariate model that predicted sustained virological response and nonresponse at baseline and during the first 12 weeks of therapy using collected data from 186 unselected patients with chronic hepatitis C treated with peginterferon plus ribavirin. This model employed ordinal regression with similarity least squares technology to assign the probability of a given outcome. Model variables include sex, age, prior treatment status, genotype, baseline serum alanine aminotransferase levels, histologic necroinflammation and fibrosis scores and serum hepatitis C virus RNA concentration at baseline and weeks, 4, 8, and 12. A multivariate model demonstrated high performance values at all time points. At baseline, the model demonstrated a negative predictive value (NPV) and a positive predictive value (PPV) of 91% and 95%, respectively. At week 4, these values improved to 97% and 100%, respectively, with 95% sensitivity, 89% specificity and 93% accuracy. At week 4, the model was equally efficient for naïve or previously treated patients. Internal validation demonstrated 90% PPV, 94% NPV, 95% sensitivity, 88% specificity and 92% accuracy. A week 4 stopping rule for patients with chronic hepatitis C treated with peginterferon with ribavirin might be proposed by using the model developed in our study.

Adult↗
PubMed2001

Transcription-mediated amplification is more sensitive than conventional PCR-based assays for detecting residual serum HCV RNA at end of treatment.

OBJECTIVE: In patients chronically infected with hepatitis C virus (HCV) undergoing antiviral therapy, sustained virologic response is suggested by viral clearance by end of treatment (EOT). Viral clearance is defined by nondetection of serum HCV RNA, usually by qualitative PCR-based assays with limits of detection ranging from 100 to 1000 copies/ml. However, some individuals relapse after achieving apparent viral clearance by EOT. These individuals may have low levels of viremia not detected by current PCR methods. The aim of this retrospective study was to determine whether the Bayer HCV RNA Qualitative Assay, which employs Transcription Mediated Amplification (TMA) and detects 50 HCV RNA copies/ml, could detect residual serum HCV RNA in patients who achieved apparent viral clearance by EOT and subsequently relapsed. METHODS: Samples were obtained at EOT (wk 24 or 48) and follow-up (wk 24-26 posttreatment) from 97 patients treated for HCV (78 relapsing patients, 19 sustained responders). All samples in which HCV RNA was not detected by PCR were tested in a blinded manner for HCV RNA by the TMA-based assay. RESULTS: HCV RNA was detected by the TMA-based assay in 27 (34.6%) EOT and 76 (97.4%) follow-up samples from relapsing patients, but not in any of the EOT or follow-up samples from sustained responders. CONCLUSION: Residual serum HCV RNA was detected by the TMA-based assay in EOT samples from 34.6% of patients that had achieved apparent viral clearance by PCR. The detection of HCV RNA by the TMA-based assay could help redefine EOT response and assist in the antiviral management of HCV infection.

Antiviral Agents↗
PubMed1999

Abnormal Fhit expression in malignant and premalignant lesions of the cervix.

Genetic analysis of cervical cancer has demonstrated frequent allelic loss in the 3p chromosomal region. The newly described gene FHIT is located at chromosome region 3p14.2, and its expression has been demonstrated previously by reverse transcription-PCR to be abnormal in a majority of cervical cancer cell lines. In this study, 98 different lesions of the cervix were examined for Fhit expression by immunohistochemical staining. Whereas normal cervical epithelium demonstrated diffuse, moderate to intense cytoplasmic staining, many pathological lesions of the cervix displayed reduced or absent Fhit expression. Sixty-one percent of squamous carcinomas and 40% of adenocarcinomas of the cervix had abnormal Fhit expression. Sixty-five preneoplastic lesions of the cervix were examined. Eleven of 33 high-grade squamous intraepithelial lesions and 1 of 12 low-grade squamous intraepithelial lesions had abnormal Fhit expression. In summary, Fhit expression is frequently abnormal in both glandular and squamous cervical cancers, with a higher frequency of Fhit alterations observed in squamous lesions. In addition, abnormal Fhit expression can be detected in some preneoplastic lesions of the ectocervix. Alterations in Fhit expression may be an important marker of early progression in the development of cancers of the cervix.

Acid Anhydride Hydrolases↗
PubMed1999

Frequent loss of KAI1 expression in squamous and lymphoid neoplasms. An immunohistochemical study of archival tissues.

The metastasis suppressor gene KAI1 was identified by its ability to inhibit the formation of pulmonary metastases in experimental models for prostatic carcinoma. Down-regulation of this gene may be correlated with the invasive phenotype in melanomas and colon and bladder carcinomas and with the metastatic phenotype in carcinomas of the lung, breast, prostate, and pancreas. The goal of our study was to establish an immunohistochemical method to detect KAI1 expression in archival tissues. Using cell lines with known KAI1 levels and paraffin-embedded KAI1 positive tissues as controls, we observed strong membrane staining in lymphoid follicular centers and squamous epithelia. We then demonstrated the utility of our assay by studying KAI1 expression in 34 lymphoid and 57 squamous lesions. All eight reactive lymph nodes were KAI1 positive. In contrast, three of 13 follicular small cleaved and five of 13 diffuse large cell lymphomas were KAI1 negative. Seventy-nine percent (37 of 47) of invasive squamous cell carcinomas from the lung (n = 15), head and neck (n = 18), and cervix (n = 14) showed extensive KAI1 down-regulation. Loss of KAI1 expression was also found in a subset of 10 high-grade cervical dysplasias. Our data show that (i) immunohistochemistry is a suitable technique for evaluating KAI1 expression in archival tissues; (ii) KAI1 was not expressed in a subset of both low-grade and high-grade lymphomas; and (iii) there was extensive down-regulation of KAI1 in squamous cell carcinomas, suggestive of an important role of the gene in the suppression of invasion in these malignancies.

Animals↗
PubMed1997

Factors that influence the collection and engraftment of allogeneic peripheral-blood stem cells in patients with hematologic malignancies.

PURPOSE: To determine the number of CD34+ cells associated with a high probability of rapid engraftment after allogeneic peripheral-blood stem-cell (PBSC) transplant, and to examine the relationship between certain donor characteristics and the effectiveness of PBSC mobilization. PATIENTS AND METHODS: Between December 1994 and July 1996, we treated 47 patients who had resistant hematologic neoplasms with myeloablative therapy followed by transplantation of allogeneic PBSC collected from histocompatible siblings after mobilization with granulocyte colony-stimulating factor (G-CSF). Expression of CD34 was determined by flow cytometry. RESULTS: Engraftment was rapid and similar to that observed following autologous PBSC transplant, with an absolute neutrophil count (ANC) greater than 500/microL and platelet count greater than 20,000/microL on median days +9 and +11, respectively. The pace of hematologic recovery correlated with the number of hematopoietic progenitors transplanted, so that patients who received greater than 5 x 10(6) CD34+ cells/kg recipient weight had a 95% likelihood of neutrophil and platelet recovery by day +15. Baseline (precytokine) CD34+ cells per milliliter of donor peripheral blood and total G-CSF dose (donor weight x 10 micrograms/kg) correlated with the number of CD34+ cells collected (R2 = .24 and P = .0009, and R2 = .24 and P < .0001, respectively). Donor age and sex did not effect mobilization. CONCLUSION: Following allogeneic PBSC transplant, patients who received greater than 5 x 10(6) CD34+ cells/ kg recipient weight had a high probability of rapid engraftment. Donors with low baseline levels of circulating progenitors (< 2,000 CD34+ cells/mL blood) and those who received lower total doses of G-CSF were less likely to be effectively mobilized. For donors with low baseline CD34+ counts, higher doses of G-CSF might improve mobilization. Baseline CD34+ counts and total G-CSF dose accounted for less than half of the variation in CD34+ cells collected, which indicates that other, as yet unidentified, factors play an important role in determining the effectiveness of mobilization.

Adolescent↗
PubMed1996

Cutaneous blood-flow patterns in free flaps determined by laser Doppler flowmetry.

Accurate monitoring of tissue perfusion in microvascular surgery is paramount to flap survival. Many methods have been proposed for monitoring of flaps, but none have achieved widespread acceptance. The laser Doppler has been shown to be beneficial in monitoring flap perfusion. Trends have been noted in laser Doppler measurements over time in free TRAM, free latissimus dorsi, and free iliac-crest osteomyocutaneous flaps. TRAM flaps demonstrated a slow increase in the laser Doppler index (LDI), with a peak increase in skin blood flow of over 600 percent at 52 to 80 hr postoperatively (LDI 6.77 +/- 3.51), and then a gradual decline to previous baseline. Latissimus dorsi flaps also demonstrated a slow increase until about 80 hr postoperatively (LDI 9.8 +/- 10.65), indicating an increase in skin blood flow of almost 900 percent. Iliac-crest osteomyocutaneous free flaps had a slow increase in blood flow until approximately 70 hr postoperatively, when the LDI (5.5) increased, representing an increase in skin blood flow of over 500 percent. These changes in skin blood flow over time, seen with continuous laser Doppler measurements, depict the dynamic nature of skin blood flow and allow predictive patterns to be established, instead of single normal values, by which to gauge adequate flap perfusion.

Adolescent↗
PubMed1991

Revascularization of an ischemic limb by use of a muscle pedicle flap: a rabbit model.

A rabbit model of hind limb ischemia was designed to demonstrate that new, hemodynamically significant arterial connections will develop between ischemic skeletal muscle and an independently perfused muscle pedicle flap. The right common iliac artery was divided in 15 rabbits. In eight rabbits a muscle flap based on the left deep inferior epigastric artery was transposed to the right thigh (flap group). In seven rabbits a sham operation was performed where the flap was sutured to the abdominal wall (sham group). After 7 days angiography demonstrated arterial connections between the flap and the native limb circulation in all of the flap group animals. The flap increased muscle perfusion in the ischemic limb (2.99 ml/100 gm muscle/minute in the flap group, vs 2.06 ml/100 gm muscle/minute in the sham group, p less than 0.005). Hemodynamically significant vascular connections will develop between a well-perfused muscle flap and an ischemic limb. The augmentation in perfusion provided by these connections can be quantified.

Animals↗
PubMed1986

Spontaneous hydrogen peroxide release from alveolar macrophages of some cigarette smokers.

Alveolar macrophages were retrieved by bronchoalveolar lavage (BAL) from 30 patients, 24 smokers and six nonsmokers. The macrophages were separated from other cells in the BAL fluid by glass adherence. The amount of hydrogen peroxide released into the media by these macrophages was then measured by a new method of determining hydrogen peroxide concentration. Two groups were found. Group 1, who did not spontaneously release hydrogen peroxide, were mostly nonsmokers (six of nine), and group 2, who spontaneously secreted hydrogen peroxide (87.5 +/- 17.08 nmol/10(6) macrophages [mean +/- SEM]), were all smokers (21 of 21). When the alveolar macrophages in group 1 were stimulated with phorbol myristate acetate, they secreted as much hydrogen peroxide as the stimulated macrophages of group 2 (group 1: 125.0 +/- 92.08 nmol/10(6) macrophages, group 2: 116.7 +/- 14.82 nmol/10(6) macrophages). We conclude that there is a subset of smokers whose alveolar macrophages spontaneously release hydrogen peroxide.

Adult↗
PubMed1982

Early social deprivation and the ontogeny of unrestricted social behavior in the laboratory rat.

The unrestricted adult social and nonsocial behavior of albino rats isolated from 21 to 70 days of age was compared with the behavior of rats receiving normal social experience. Isolated animals exhibited aberrant self-manipulative behaviors during the period of isolation, and both isolate-reared males and females were more aggressive than their group-reared counterparts. The hypothesis that females are buffered against the effects of social isolation received little support. Numerous gender differences and differences in the gender of the object of social response were found for both isolate- and group-reared rats. Gender and Rearing Conditions were relatively independent influences on behavior with few Gender x Treatment interactions reaching significance.

Aggression↗
PubMedDate not supplied

Microcomputer database management for surgical residents.

Surgical residents must record procedures performed and may choose to keep files of photographic slides, bibliographic references, and a curriculum vitae. Four databases that store this information are produced with an inexpensive and easily obtained microcomputer software program. A surgical procedure database is modeled after the procedure list recommended by surgical boards. This list can be viewed while one enters data, thereby enabling production of accurate and complete records. In the second database, photographic slides are assigned sequence numbers and slide content is designated using both procedure codes and key words, allowing structured and personal recall of data. Data can be printed in many report formats, including that used by the boards of surgery for final submission of reports of residents' operations at the completion of residency. The bibliographic and CV databases contain highly segmented citation data. This structure enables manipulation of data to satisfy the sequence requirements of journals or institutions to which articles or CV are submitted. Database maintenance consumes a few minutes daily and requires a minimum of experience with computers. By providing ease of access to organized data, these databases enhance the potential for critical review of clinical experience by both residents and program directors.

General Surgery↗