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Biomedical subjects

J Howell

Publications and source records attributed to J Howell.

At least 19 recordsLinked to original sources
PubMed2005

Faecal calprotectin in the assessment of Crohn's disease activity.

BACKGROUND: Clinical and laboratory assessment of activity in Crohn's disease (CD) correlate poorly with endoscopic findings. Calprotectin is a calcium-binding protein abundant in neutrophil cytosol, and extremely stable in faeces. Faecal calprotectin (FC) is an excellent surrogate marker of neutrophil influx into the bowel lumen. AIM: To assess whether FC concentration from a spot stool sample reliably detects active inflammation in patients with CD. DESIGN: Cross-sectional comparative study. METHODS: Subjects had a previously confirmed diagnosis of CD and were suspected on clinical grounds to be in the midst of a relapse. Thirty-five entered the study; they underwent radiolabelled white cell scanning (WCS) and had a stool sample collected for calprotectin measurement on the same day. A Crohn's disease activity index (CDAI) was also calculated for each. The WCS scans were scored at six standard sites to give a mean total, 'extent', 'severity' and 'combined extent and severity' scores. RESULTS: FC was significantly and positively correlated with mean total (r = 0.73, p < 0.001), 'extent' (r = 0.71, p < 0.001), 'severity' (r = 0.64, p < 0.001) and combined 'extent and severity' WCS scores (r = 0.71, p < 0.001). A cut-off of faecal calprotectin > 100 microg/g gave a sensitivity of 80%, specificity of 67%, positive predictive value of 87% and a negative predictive value of 64% in identifying those with and without any inflammation on WCS. There was, however, no significant correlation between CDAI and mean total WCS score (r = 0.21, p = 0.24), nor between CDAI and FC (r = 0.33, p = 0.06). DISCUSSION: While the CDAI does not accurately reflect inflammatory activity in CD, a one-off FC reliably detects the presence or absence of intestinal inflammation in adult patients with CD, compared to WCS.

Adult↗
PubMed2004

Embolus of surgical adhesive to the extremities causing acute ischemia: report of two cases.

We present 2 cases in which a surgical adhesive embolized to the extremities. In the first case an adhesive was successfully used in the repair of a DeBakey type I aortic dissection. The patient was seen 2 months postoperatively with acute lower extremity ischemia, and a large piece of adhesive was extracted from the iliac and femoral arteries at embolectomy. In the second case the adhesive was used to seal a pericardial patch during repair of a ventricular septal defect. This patient was seen 1 day postoperatively with acute arm ischemia, and the adhesive particle was extracted from the brachial artery during embolectomy.

Acute Disease↗
PubMed2001

Bacterial counts in experimental, contaminated crush wounds irrigated with various concentrations of cefazolin and penicillin.

The objective of this study was to determine if three different concentrations of cefazolin and penicillin irrigation solutions reduce quantitative bacterial counts in experimental crush wounds contaminated with multiple species of bacteria. The design used was a randomized, blinded, experimental animal study. An animal bite wound model was created by innoculating crushed incisions with three species of bacteria. Four paravertebral incisions extending to deep fascia were created in each of twelve anesthetized albino guinea pigs. Wound edges were clamped with a hemostat for five seconds to create crushed, devitalized tissue within each wound. Wounds were inoculated with 0.4 mL of a standard solution of Staphylococcus aureus, Bacterioides fragilis, and Pasturella multocida and covered. Four hours after inoculation, each wound was scrubbed for 30 seconds with 20% poloxamer 188 and then irrigated with 100 mL of one of four solutions: normal saline solution (control); cefazolin (CZ) 2 mg/mL, plus penicillin G (PCN) 200 units/mL (low dose); CZ 10 mg/mL, plus PCN 2,000 units/mL (intermediate dose); and CZ 50 mg/mL, plus PCN 20, 000 units/mL (high dose). Investigators were blinded to the solutions used. Wounds were covered with a vapor-permeable dressing. Six days after treatment, each wound was examined for signs of infection and then excised for quantitative bacteriologic analysis. Colony counts were reported as counts per gram of tissue. Wounds in the four irrigation solution groups were compared using ANOVA. A log difference of 3 was considered significant. The average log total bacteria/gram tissue for the four groups were: control, 4.35 (95% CI; 1.01); low dose, 4.09 (95% CI; 1.42); intermediate dose, 4.47 (95% CI; 1.27); and high dose, 3.45 (95% CI; 1.33). No wounds in the high-dose group had any clinical signs of infection, whereas 50% of wounds in the intermediate dose group, 42% in the low dose group, and 33% in the control group had either erythema, induration, or purulence. There were no statistically significant differences in the bacterial counts/gram tissue or clinical infection rates in any of the groups. A formal trend analysis failed to find a significant linear trend for decreasing bacterial counts for either antibiotic. In this experimental bite wound model containing contaminated, crushed tissue, irrigation with various solutions of cefazolin plus penicillin G did not reduce quantitative bacterial counts more than 3.1 log total bacteria/gram tissue.

Animals↗
PubMed2001

Pharmacologic insights into the future of trastuzumab.

A combination of factors has been responsible for improvements in cancer survival and cure rates. In addition to new therapies with novel/genetic targets, these include improvements in drug delivery, new schedules/sequencing of drug administration and the identification of combination therapies with greater activity/dose density than existing regimens. The recognition that such criteria can affect treatment outcome has led to their incorporation into clinical trials of new drugs. Furthermore, pharmacokinetic and pharmacodynamic parameters have become increasingly important for the rational selection of dose, administration route and schedule. The humanized monoclonal antibody trastuzumab (Herceptin) has been rationally developed to target the human epidermal growth factor receptor-2 (HER2), which is overexpressed in 20%-30% of breast cancers and is associated with poor prognosis. Trastuzumab when administered i.v. on a weekly schedule either alone or in combination with taxanes, improves survival of women with HER2-positive metastatic breast cancer. Based upon pharmacokinetic considerations, current studies are examining whether trastuzumab can be administered i.v. every three weeks or by the s.c. route. These regimens would have advantages for patients and medical staff in terms of acceptability, ease of administration and, potentially, cost effectiveness. Furthermore, various combinations of trastuzumab and chemotherapeutic agents are being explored with the aim of identifying the optimal combination regimen for clinical use. The rationale for these various studies and the studies themselves are described.

Antibodies, Monoclonal↗
PubMed2001

Pain on injection of prilocaine plain vs. lidocaine with epinephrine. A prospective double-blind study.

BACKGROUND: Prilocaine has been described as causing less pain on injection than lidocaine with epinephrine, possibly because of the higher pH of the prilocaine anesthetic solution. METHODS: Three hundred ten consecutively seen patients in a general practice received a total of 334 maxillary buccal infiltration or inferior alveolar block injections, administered under clinical conditions by one of two dentists. Immediately afterward, patients rated the pain from each injection on a six-point scale. Twenty of these patients (in 21 separate appointments) received, and were asked to rate the pain associated with, a second injection of a contralateral tooth. The authors analyzed the pain response by operator, location of injection, patient's age, patient's sex and anesthetic. RESULTS: The difference in perceived pain between lidocaine and prilocaine was not statistically significant. Regardless of the anesthetic used, the perceived pain was usually no more than mild. Of 334 injections, 292 (87 percent) were rated as causing either no pain or mild pain. CONCLUSIONS: Under clinical conditions, there is no statistically significant difference between injection pain associated with prilocaine plain vs. that associated with lidocaine with 1:100,000 epinephrine. CLINICAL IMPLICATIONS: Since there is no significant difference in associated pain on injection between prilocaine plain and lidocaine with 1:100,000 epinephrine, dentists may prefer lidocaine with epinephrine. Since there is less anesthetic in each cartridge of lidocaine, it may require the use of less anesthetic per patient, and the vasoconstrictor can prolong its duration.

Adolescent↗
PubMed2000

Regioselective enzymatic aminoacylation of lobucavir to give an intermediate for lobucavir prodrug.

Synthesis of lobucavir prodrug, L-valine, [(1S,2R,3R)-3-(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)-2-(hydroxymethyl) cyclobutyl]methyl ester monohydrochloride (BMS 233866), requires regioselective coupling of one of the two hydroxyl groups of lobucavir (BMS 180194) with valine. Either hydroxyl group of lobucavir could be selectively aminoacylated with valine by using enzymatic reactions. N-[(Phenylmethoxy)carbonyl]-L-valine, [(1R,2R,4S)-2-(2-amino-6-oxo-1H-purin-9-yl)-4-(hydroxymethyl)cyclobutyl]methyl ester (3, 82.5% yield), was obtained by selective hydrolysis of N,N'-bis[(phenylmethoxy)carbonyl]bis[L-valine], O,O'-[(1S,2R,3R)-3-(2-amino-6-oxo-1H-purin-9-yl)cyclobuta-1,2-diyl]methyl ester (1) with lipase M, and L-valine, [(1R,2R,4S)-2-(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)-4-(hydroxymethyl)cyclobutyl]methyl ester monohydrochloride (4, 87% yield) was obtained by hydrolysis of bis[L-valine], O,O'-[(1S,2R,3R)-3-(2-amino-6-oxo-1H-purin-9-yl)cyclobuta-1,2-diyl]methyl ester, dihydrochloride (2), with lipase from Candida cylindracea. The final intermediate for lobucavir prodrug, N-[(phenylmethoxy)carbonyl]-L-valine, [(1S,2R,4R)-3-(2-amino-6-oxo-1H-purin-9-yl)-2-(hydroxymethyl)cyclobutyl]methyl ester (5), could be obtained by transesterification of lobucavir using ChiroCLEC BL (61% yield), or more selectively by using immobilized lipase from Pseudomonas cepacia (84% yield).

Acylation↗
PubMed2000

Emergency medicine resident documentation: results of the 1999 american board of emergency medicine in-training examination survey.

OBJECTIVES: To assess how emergency medicine (EM) residents perform medical record documentation, and how well they comply with Health Care Financing Administration (HCFA) Medicare charting guidelines. In addition, the study investigated their abilities and confidence with billing and coding of patient care visits and procedures performed in the emergency department (ED). Finally, the study assessed their exposure to both online faculty instruction and formal didactic experience with this component of their curriculum. METHODS: A survey was conducted consisting of closed-ended questions investigating medical record documentation in the ED. The survey was distributed to all EM residents, EM-internal medicine, and EM-pediatrics residents taking the 1999 American Board of Emergency Medicine (ABEM) In-Training examination. Five EM residents and the Society for Academic Emergency Medicine (SAEM) board of directors prevalidated the survey. Summary statistics were calculated and resident levels were compared for each question using either chi-square or Fisher's exact test. Alpha was 0.05 for all comparisons. RESULTS: Completed surveys were returned from 88.5% of the respondents. A small minority of the residents code their own charts (6%). Patient encounters are most frequently documented on free-form handwritten charts (38%), and a total of 76% of the respondents reported using handwritten forms as a portion of the patient's final chart. Twenty-nine percent reported delays of more than 30 minutes to access medical record information for a patient evaluated in their ED within the previous 72 hours. Twenty-five percent "never" record their supervising faculty's involvement in patient care, and another 25% record that information "1-25%" of the time. Seventy-nine percent are "never" or "rarely" requested by their faculty to clarify or add to medical records for billing purposes. Only 4% of the EM residents were "extremely confident" in their ability to perform billing and coding, and more than 80% reported not knowing the physician charges for services or procedures performed in the ED. CONCLUSIONS: The handwritten chart is the most widely used method of patient care documentation, either entirely or as a component of a templated chart. Most EM residents do not document their faculty's participation in the care of patients. This could lead to overestimation of faculty noncompliance with HCFA billing guidelines. Emergency medicine residents are not confident in their knowledge of medical record documentation and coding procedures, nor of charges for services rendered in the ED.

Adult↗
PubMed1996

Altering anticoagulation therapy: a survey of physicians.

Patients who take antithrombotic medications, such as warfarin sodium or aspirin, are more likely than others to experience bleeding problems after some dental treatments. Withdrawing the medication before treatment, however, may place these patients at risk of medical complications. The authors surveyed physicians about the conditions under which such pharmacotherapies should be altered. They not only found a difference of opinion among the respondents, but also learned that many respondents misunderstood the nature of certain dental procedures and the likelihood that those procedures would cause significant postoperative bleeding.

Anticoagulants↗
PubMed1996

Failure of chloro-S-triazine-derived compounds to induce estrogen receptor-mediated responses in vivo and in vitro.

The potential estrogenic activities of atrazine and simazine were investigated in vivo using the immature female Sprague-Dawley rat uterus and in vitro using the estrogen-responsive MCF-7 human breast cancer cell line and the estrogen-dependent recombinant yeast strain PL3. Animals that were dosed with 50, 150, or 300 mg/kg of atrazine or simazine alone for 3 consecutive days did not exhibit any significant increases in uterine wet weight while decreases in cytosolic progesterone receptor (PR) binding levels and uterine peroxidase activity were observed. 17 beta-estradiol (E2)-induced increases in uterine wet weight were not significantly affected by cotreatment with either chemical; however, some dose-independent decreases in E2-induced cytosolic PR binding and uterine peroxidase activity were observed. In vitro, atrazine and simazine did not affect basal or E2-induced MCF-7 cell proliferation or the formation of nuclear PR-DNA complexes as determined by gel electrophoretic mobility shift assays. In addition, these chloro-S-triazines did not display agonist activity or antagonize E2-induced luciferase activity in MCF-7 cells transiently transfected with a Gal4-human estrogen receptor chimera (Gal4-HEGO) and a Gal4-regulated luciferase reporter gene (17m5-G-Luc). Moreover, the estrogen-dependent PL3 yeast strain was not capable of growth on minimal media supplemented with atrazine or simazine in place of E2. Collectively, these results indicate that the reported estrogenic and antiestrogenic effects elicited by these chemicals are not mediated by the estrogen receptor.

Animals↗
PubMed1995

Naringenin: a weakly estrogenic bioflavonoid that exhibits antiestrogenic activity.

Treatment of immature 21-day-old female Sprague-Dawley rats with 17 beta-estradiol (E2) (0.5 microgram/rat) caused a significant increase in uterine wet weight, DNA synthesis, progesterone receptor (PR) binding, and peroxidase activity. At doses as high as 40 mg/rat, the bioflavonoid naringenin did not cause a significant increase in any of these E2-induced responses. However, in rats cotreated with E2 (0.5 microgram/rat) plus naringenin (30 mg/rat); there was a significant decrease in E2-induced uterine wet weight, DNA synthesis, PR binding, and peroxidase activity, indicating that naringenin exhibits antiestrogenic activity in the immature rodent uterus. The binding of uterine nuclear extracts to a 32P-labeled estrogen responsive element (ERE) or progesterone responsive element (PRE) was determined using gel electrophoretic band shift assays. Incubation of [32P]ERE with uterine nuclear extracts from rats treated with naringenin or E2 resulted in the formation of estrogen receptor (ER):ERE complexes; a higher mobility complex was prominent in the extracts from E2-treated rats, whereas a lower mobility complex was observed using nuclear extracts from naringenin-treated animals. There was a significant decrease in the intensity of the E2-induced complex using nuclear extracts from rats treated with E2 plus naringenin. In contrast, transformed cytosol from control rats gave an intense ER:ERE complex, whereas the intensity of the band was decreased markedly using transformed uterine cytosol from treated rats. Formation of a PR:PRE complex was also determined using transformed uterine cytosol. Cytosol from E2-treated rats gave an intense retarded band, whereas only weak bands were observed using cytosols from DMSO- (solvent), naringenin-, or naringenin plus E2-treated cells. The results of in vitro studies showed that 1 nM E2 increased (3- to 4-fold) the growth of MCF-7 human breast cancer cells, whereas 1-1000 nM naringenin had no effect on cell proliferation. In cells cotreated with 1 nM E2 plus 1000 nM naringenin, there was a significant decrease in E2-induced cell growth. In MCF-7 cells transiently transfected with a pS2 promoter-regulated luciferase reporter gene, naringenin exhibited weak estrogenic activity. In cells cotreated with 0.1 or 1.0 microM naringenin plus 1 nM E2, naringenin inhibited E2-induced luciferase activity. The results of these studies confirmed that naringenin is a weak estrogen that also exhibits partial antiestrogenic activity in the female rat uterus and MCF-7 human breast cancer cells.

Animals↗