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Biomedical subjects

T Russell

Publications and source records attributed to T Russell.

At least 19 recordsLinked to original sources
PubMed1999

Ultraviolet radiation induces p16CDKN2A expression in human skin.

The loss of the tumor suppressor gene product p16 in melanoma is well documented, although the normal physiological function of p16 in skin melanocytes is unknown. In this report, we demonstrate that when human skin was irradiated with suberythemal doses of UV radiation, levels of p16 were dramatically increased by 16 h postirradiation, peaking at 24 h, and declining by 72 h. p16 was expressed in the nucleus and cytoplasm of melanocytes and keratinocytes within the epidermis, and the pattern of p16 expression within the epidermis was dependent on the penetrative ability of the different UV wavebands. The existence of a UV-induced response pathway involving up-regulated p16 expression may provide a mechanism linking the loss of p16 and UV exposure with the development of melanoma.

Cyclin-Dependent Kinase Inhibitor p16↗
PubMed1999

Cardiovascular safety of fexofenadine HCl.

Fexofenadine HCl is the acid metabolite of terfenadine (Seldane). The effect of this recently approved nonsedating antihistamine on the corrected QT interval (QTc) was evaluated in dose-tolerance, safety, and drug-interaction studies with healthy volunteers, and in clinical studies in patients with seasonal allergic rhinitis (SAR). Twelve-lead electrocardiographic data were collected once before and after dosing or serially throughout these studies. Outliers were defined as QTc > 440 ms with a > or = 10 ms increase from baseline. The recommended fexofenadine HCl dose is 60 mg twice daily. Fexofenadine HCl doses up to 800 mg once daily or 690 mg twice daily for 28 days resulted in no dose-related increases in QTc. Longer term studies indicated no statistically significant QTc increases compared with placebo in patients receiving fexofenadine HCl 80 mg twice daily for 3 months, 60 mg twice daily for 6 months, or 240 mg once daily for 12 months. Interaction studies showed no significant increases in QTc when fexofenadine HCl 120 mg twice daily was administered in combination with erythromycin (500 mg 3 times daily) or ketoconazole (400 mg once daily) after dosing to steady state (6.5 days). Clinical trials in patients with SAR (n = 1,160) treated with 40, 60, 120, or 240 mg twice-daily fexofenadine HCl or placebo indicated no dose-related increases in QTc and no statistically significant increases in mean QTc compared with placebo. In controlled trials with approximately 6,000 persons, no case of fexofenadine-associated torsades de pointes was observed. The frequency and magnitude of QTc outliers were similar between fexofenadine HCl and placebo in all studies. Based on a large clinical database, we conclude that fexofenadine HCl has no significant effect on QTc, even at doses > 10-fold higher than that is efficacious for SAR.

Double-Blind Method↗
PubMed1999

Bifidobacterial supplementation reduces the incidence of necrotizing enterocolitis in a neonatal rat model.

BACKGROUND & AIMS: Neonatal necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease of premature infants partly caused by intestinal bacterial proliferation. Because bifidobacteria are thought to reduce the risk for intestinal disturbances associated with pathogenic bacterial colonization, we hypothesized that exogenous bifidobacterial supplementation to newborn rats would result in intestinal colonization and a reduction in the incidence of neonatal NEC. METHODS: Newborn rat pups were given Bifidobacterium infantis (10(9) organisms per animal daily), Escherichia coli, or saline control and exposed to the NEC protocol consisting of formula feeding (Esbilac; 200 cal. kg(-1). day(-1)) and asphyxia (100% N(2) for 50 seconds followed by cold exposure for 10 minutes). Outcome measures included stool and intestinal microbiological evaluation, gross and histological evidence of NEC, plasma endotoxin concentration, intestinal phospholipase A(2) expression, and estimation of intestinal mucosal permeability. RESULTS: Bifidobacterial supplementation resulted in intestinal colonization by 24 hours and appearance in stool samples by 48 hours. Bifidobacteria-supplemented animals had a significant reduction in the incidence of NEC compared with controls and E. coli-treated animals (NEC, 7/24 B. infantis vs. 19/27 control vs. 16/23 E. coli; P < 0.01). Plasma endotoxin and intestinal phospholipase A(2) expression were lower in bifidobacteria-treated pups than in controls, supporting the role of bacterial translocation and activation of the inflammatory cascade in the pathophysiology of NEC. CONCLUSIONS: Intestinal bifidobacterial colonization reduces the risk of NEC in newborn rats.

Animals↗
PubMed1999

Cardiovascular safety of fexofenadine HCl.

BACKGROUND: Certain first- and second-generation H1-receptor antagonists are associated with prolongation of the corrected QT interval (QTc) and, in rare instances, with ventricular dysrhythmias, including torsades de pointes ventricular tachycardia. OBJECTIVE: To assess the effect of fexofenadine HCl, a new non-sedating antihistamine, on QTc. METHODS: Dose-tolerance, safety, and drug-interaction studies with healthy volunteers; and clinical efficacy studies with seasonal allergic rhinitis patients were conducted. Twelve-lead ECG data were collected pre- and postdosing or serially throughout these studies. Outliers were defined as QTc >440 msec with a >/=10 msec increase from baseline. RESULTS: Fexofenadine HCl at single doses up to 800 mg q.d. (once daily) and multiple doses up to 690 mg b.d. for 28 days in healthy volunteers resulted in no increases in QTc (recommended dose range is 120-180 mg daily); QTc changes were similar to placebo. Compared with placebo, there were no statistically significant QTc increases in patients receiving fexofenadine HCl 80 mg b.d. for 3 months, 60 mg b. d. for 6 months, or 240 mg q.d. for 12 months. No statistically significant increases in QTc were detected when fexofenadine HCl 120 mg b.d. was administered in combination with erythromycin (500 mg t. d.) or ketoconazole (400 mg q.d.) after dosing to steady-state (6.5 days). In seasonal allergic rhinitis patients (n = 1160) treated with 40, 60, 120, or 240 mg b.d. fexofenadine HCl for 2 weeks, there were no dose-related increases in QTc and no significant increases in mean QTc compared with placebo. Frequency and magnitude of QTc outliers with fexofenadine HCl and placebo were similar in all studies. No case of fexofenadine-associated torsades de pointes has been observed in controlled trial experience with more than 6000 patients. CONCLUSION: Fexofenadine HCl has been investigated more extensively for possible electrophysiological effects than any other antihistamine. Fexofenadine HCl has no significant effect on QTc, even at doses much higher than those used in clinical practice.

Dose-Response Relationship, Drug↗
PubMed1999

Assessment of QTc prolongation for non-cardiac-related drugs from a drug development perspective.

It is increasingly likely that non-cardiac-related drugs will need to be routinely analyzed for their ability to prolong cardiac repolarization. This leads to potential problems for drug companies in general and statisticians in particular. A number of issues immediately arise in regard to answering the question, "Does drug X prolong cardiac repolarization?" These include identifying what is the desired outcome, what is the dependent variable, and what analysis method should be used. The purpose of this article is bring to to light some of the issues regarding the analysis of QTc data, the advantages and disadvantages of these analysis methods, and some general recommendations.

Cardiotonic Agents↗
PubMed1998

Pharmacokinetics, pharmacodynamics, and tolerance of single- and multiple-dose fexofenadine hydrochloride in healthy male volunteers.

BACKGROUND: Fexofenadine is a selective, nonsedating H1-receptor antagonist that relieves symptoms of allergic conditions. METHODS: Two randomized, double-blind, parallel-group, placebo-controlled dose-escalation studies were performed in healthy men to determine the maximum tolerated oral dose, pharmacokinetics, pharmacodynamics, and safety of fexofenadine hydrochloride. In the first study, 87 subjects (6 in the active drug group and 2 in the placebo group) received single oral doses of fexofenadine hydrochloride ranging from 10 to 800 mg or placebo. In the second study, 32 subjects (3 in the active drug group and 1 in the placebo group) received multiple fexofenadine hydrochloride doses ranging from 20 to 690 mg or placebo twice daily for 28 1/2 days. Serial plasma and urine samples were collected. Fexofenadine concentrations were determined by HPLC and fluorescence. Wheal and flare response to intradermal histamine was used to evaluate antihistaminic activity. RESULTS: Fexofenadine hydrochloride was rapidly absorbed, reaching peak concentrations in 0.83 to 1.33 hours. Single-dose mean concentration ranged from 46 to 6383 ng/mL, and steady-state maximum plasma concentration ranged from 58 to 4677 ng/mL. Mean area under the plasma concentration-time curve was approximately proportional to dose. Oral clearance, renal clearance, and cumulative percent of drug excreted in urine were similar after single and multiple doses and were generally constant over the dose range studied. Inhibition of skin wheal and flare was shown for single doses of 40 mg and higher and for all multiple doses. No fexofenadine dose-related trends or apparent differences from placebo were found for any safety parameter. CONCLUSIONS: Fexofenadine hydrochloride was well tolerated at oral doses up to 11 times the recommended therapeutic dose. In addition, fexofenadine hydrochloride showed significant antihistaminic activity and dose-proportional pharmacokinetics over a wide dosing range.

Administration, Oral↗
PubMed1998

Attributions for positive life events predict recovery from depression among psychiatric inpatients: an investigation of the Needles and Abramson model of recovery from depression.

The authors investigated whether attributions for positive life events predict decreases in hopelessness and depressive symptoms among clinically depressed adults. Measures of attributional style, attributions for recent events, depressive symptoms, dysfunctional attitudes, hopelessness, and life events were administered to 52 depressed psychiatric inpatients treated with antidepressant medication; the measures were readministered 12 and 24 days later. Results indicated that (a) internal, stable, global attributions for recent positive events mediated a significant association between attributional style for positive life events and decreased hopelessness; (b) decreases in hopelessness mediated a significant association between internal, stable, global attributions for recent positive events and decreases in depressive symptom levels; and (c) depressotypic cognitions were not associated with decreases in either hopelessness or depressive symptom levels.

Adolescent↗
PubMed1997

Immunolocalization of cytoplasmic and myelin mcalpain in transfected Schwann cells: II. Effect of withdrawal of growth factors.

We have examined the reversal of the regulatory effect of growth factors on calpain/calpastatin activity in transfected Schwann cells (tSc) after their subsequent withdrawal. Removal of nerve growth factor (NGF) or cyclic adenosine monophosphate (cAMP) from tSc resulted in a smaller loss of mu calpain (37%) and mcalpain (36.5 %) activity compared to treated cells from which the growth factors were not withdrawn. The mu calpain activity increased approximately 12% following withdrawal of acidic fibroblast growth factor (aFGF) and basic fibroblast growth factor (bFGF) at 24 hr, while the increased mcalpain activity was more than 30-40% compared with that of cells that were continuously treated. The activity of both isoforms returned to their normal levels (untreated) at 48-72 hr following withdrawal of various growth factors, including NGF, cAMP, aFGF, bFGF, platelet-derived growth factor aa (PDGFaa), and PDGFbb. The inhibitory activity of calpastatin was greater than control following withdrawal of NGF, cAMP, PDGFaa, or PDGFbb at 24 hr and this inhibitory activity was less with treatment by aFGF and bFGF. The control activity was restored at 48 hr following withdrawal of these factors. The intensity of the cytoplasmic calpain immunoreactivity was significantly decreased in the nuclear and non-nuclear regions of the cytoplasm, respectively, following withdrawal of cAMP at 144 hr. Removal of bFGF from the medium resulted in an increase of cytoplasmic calpain immunoreactivity in the nuclear regions and cytoplasm, while there was dramatic loss of myelin calpain immunoreactivity from both the nuclear region and cytoplasm. The changes in calpain activity and immunoreactivity in tSc following withdrawal of growth factors suggest that release of calpain from membrane to cytosol may be regulated by these factors.

Animals↗
PubMed1997

Immunolocalization of cytoplasmic and myelin mcalpain in transfected Schwann cells: I. Effect of treatment with growth factors.

We have examined the effect of growth factors on the activity and localization of calpain in transfected Schwann cells (tSc). Axolemma-enriched fraction, cAMP, or NGF showed concentration-dependent inhibition of both mu calpain and mcalpain activity. In contrast, both acidic FGF and basic FGF stimulated mu calpain (37%) and mcalpain (58%) of tSC while PDGF-aa and PDGF-bb inhibited both calpain activities. The inhibitor (calpastatin) activity was approximately 90% following treatment with NGF, cAMP, PDGF-aa, and PDGF-bb compared to control while this activity was 40% with FGF-treated samples. Immunofluorescence studies indicated localization of cytoplasmic calpain in the nuclear region following growth factor treatment in the cytoplasm. Growth factor treatment caused a decrease in the intensity of calpain immunoreactivity. Treatment with cAMP or FGF resulted in strong immunoreactivity of mcalpain in the nuclear region and cytoplasm compared to untreated. The growth factors did not cause translocation of calpain to the outer surface of the cell membrane. The increased immunoreactivity seen with myelin calpain antibody was greater than cytosolic antibody. The changes seen in calpain activity and immunoreactivity following treatment with growth factors suggest that these factors may regulate calpain-calpastatin expression and translocation to the membrane for interaction with lipids for enzyme activation.

Animals↗
PubMed1996

Cervical spine surgery in patients with rheumatoid arthritis: an appraisal.

OBJECTIVES: To review the outcome of surgery undertaken to stabilise the neck in patients with rheumatoid arthritis performed over a five year period, to compare the results with those of previous reports, and to identify factors that may predict surgical outcome. METHODS: Outcome was assessed at time of discharge from hospital after surgery by review of patients' notes, and at follow up by patient interview, clinical examination, anonymous questionnaire, and cervical spine radiograph. The Ranawat classification of neurological impairment and Steinbrocker functional classification were used. RESULTS: Thirty nine patients underwent 44 procedures; 28 patients were available for review after a mean period of 29.8 months (range 12-65 months). Fourteen patients had preoperative neurological impairment and were available for follow up; 13 returned the questionnaire. Four (29%) had improved Ranawat class, nine were unchanged, and one had deteriorated. Nine (69%) reported a subjective improvement in neurological symptoms by questionnaire, even though the Ranawat class was unchanged in five. Twenty five of the patients reviewed had pain before operation; 21 returned the questionnaire. Pain relief was reported by direct questioning and questionnaire in 76% and 67% of patients, respectively. Overall, 67% felt that surgery had been successful. Surgery was more successful in producing symptomatic relief in patients with neck or radicular pain than in those with neurological deficit, but did prevent progression of neurological symptoms. CONCLUSIONS: Our results are similar to those from other centres. Overall patient satisfaction with surgery was good. Surgery was more likely to produce symptomatic relief in patients with neck or radicular pain before operation than in those with neurological deficit. The greater subjective improvement in neurological symptoms as judged by questionnaire probably reflects the relative insensitivity of the Ranawat classification in detecting change in neurological status; previous reports of poor outcome for patients with neurological symptoms who undergo surgery may in part be a reflection of the insensitivity of this method of assessment. No clear factors emerged which allowed prediction of those patients at greatest risk of operative mortality. In particular, an increased risk of neurological compromise appeared to confer no additional risk of immediate perioperative death. Our data support the suggestion that early surgery to correct symptomatic atlantoaxial subluxation may prevent progression of instability.

Adult↗
PubMed1993

A rapid manual method for CD4+ T-cell quantitation for use in developing countries.

OBJECTIVE: To evaluate a manual method (Cytosphere) for quantifying CD4+ T-cell numbers. DESIGN: Cross-sectional study of HIV-1-seronegative and HIV-1-seropositive individuals evaluated for absolute CD4 counts by both standardized flow cytometric measurements and manual Cytosphere technology using a hemacytometer. SETTING: University research hospitals in both the United States and Africa. PATIENTS, PARTICIPANTS: Blood specimens from 382 patients were evaluated. These were broken down into 294 samples obtained from HIV-1-seropositive patients and 88 samples obtained from HIV-1-seronegative patients. INTERVENTIONS: None. OUTCOME MEASURED: Absolute CD4 cell number. RESULTS: Evaluation of samples obtained from HIV-1 patients in both the United States and Africa demonstrated an overall correlation of the Cytosphere assay with flow cytometry of 0.912 (95% confidence interval, 0.895-0.928; P < 0.001). When samples were stratified based on CD4+ T-cell counts determined by flow cytometry, the Cytosphere assay had a 96% predictive value for correctly identifying individuals with CD4 T-cell counts > 200 x 10(6)/l and a 92% predictive value for correctly identifying individuals with CD4 T-cell counts < 200 x 10(6)/l. CONCLUSIONS: This assay appears to have the potential for the quantitation of CD4 cells in the limited laboratory facilities in developing countries and to have a strong correlation with standard flow cytometric technology.

Adult↗
PubMed1993

The Halifax Interlaminar Clamp for posterior cervical fusion: initial experience in the United Kingdom.

A retrospective review of patients who underwent posterior cervical stabilization with Halifax Interlaminar Clamps in four neurosurgical centers in the United Kingdom was performed. Satisfactory bone fusion without complication occurred in all patients in whom lower cervical spinal stabilization (C3-C7) was performed. Complications occurred in 14 of 45 patients undergoing atlantoaxial arthrodesis. In 10 patients, one of the screws loosened, and in 4 patients, one of the clamps disengaged; additional operations to achieve bone fusion were required in 9 patients (20%). The Halifax Interlaminar Clamp is safe and effective for posterior stabilization in the lower cervical spine; there is a significant failure rate associated with its use for atlantoaxial arthrodesis.

Arthritis, Rheumatoid↗
PubMed1992

The use of clearplan home ovulation detection kits in unexplained and male factor infertility.

One hundred and five couples with unexplained infertility and 43 couples whose infertility was thought to be due to reduced sperm motility were recruited. The median duration of infertility was 36 months (range 12-168). Couples were randomly allocated to either using Clearplan home ovulation detection kits for 3 cycles or were advised about the optimal time during their menstrual cycle to achieve a pregnancy. The clinical details of the 2 groups were similar. In couples with unexplained infertility over the study period 10 (20.4%) in the Clearplan group and 9 (16%) in the control group conceived with 58% of pregnancies occurring in the first cycle. In couples with reduced sperm motility, the results were disappointing with only 2 (8%) pregnancies in the Clearplan group and 2 (11.1%) in the controls. Assisted reproduction technology may not be justified as the first line of management in patients with unexplained infertility.

Adult↗
PubMed1991

Calcium-activated neutral proteinase (CANP; calpain) activity in Schwann cells: immunofluorescence localization and compartmentation of mu- and mCANP.

Calcium-activated neutral proteinase (CANP) activity was determined in cytosolic and membranous subcellular fractions of transformed Schwann cells (tSc). The muM and mM Ca(2+)-sensitive (mu- and mCANP) forms of CANP were separated by DEAE and phenyl Sepharose column chromatography, the latter step enabling removal of the endogenous inhibitor calpastatin. The tSc contained more muCANP than the mM isoform. More than 75% of mCANP activity was membrane-associated and 20% was cytosolic. In contrast, approximately 80% of muCANP was cytosolic and 15% was membranous. Triton X-100 stimulated activity of the whole homogenate and of the membrane pellet but did not stimulate CANP activity in the cytosolic fraction. Immunohistochemical distribution of mM enzyme was studied in both fixed and permeabilized tSc with cytosolic (anti-cyt-mCANP) and myelin (anti-my-mCANP) antibodies. Live cells (non-permeabilized) stained with anti-my-mCANP had a single filamentous ring circumscribing individual cells. Permeabilized cells treated with anti-my-mCANP had immunoreactive deposits throughout the intracellular space but sparing the perinuclear region. No immunohistochemical staining was detected when live cells were exposed to anti-cyt-mCANP whereas permeabilized cells had extensive intracellular staining with the most intense immunoreactivity in the perinuclear region. Our results indicate that both forms of CANP are present in tSc and that the activity of most of the muCANP is cytosolic while mCANP is particulate.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1991

The clinical value of Clearplan home ovulation detection kits in infertility practice.

A home ovulation testing kit, Clearplan, that detects the urinary luteinizing hormone (LH) surge was used by 32 patients on a donor insemination programme for 50 cycles to indicate when to first attend the clinic for a serum LH test to determine ovulation. Using Clearplan significantly reduced the number of clinic attendances (4.06 +/- 1.5) compared to the preceding control cycle (7.06 +/- 2.0 p less than 0.001). One serum LH peak was missed using Clearplan. Ovulation was predicted within 2 days of the serum LH surge in 77% of cycles. Home ovulation determination has the potential to reduce the stress and cost of fertility programmes.

Appointments and Schedules↗
PubMed1990

Giant malignant tumors of the anus. A strategy for management.

Four homosexual male patients with giant anal carcinomas, ranging from 10 to 17 cm in diameter, are presented. These patients were not candidates for abdominoperineal resection because of fixation to adjacent structures. Common symptoms included pain, sepsis, anemia, incontinence, and weight loss. Diverting colostomy was performed in all patients. Two of the four patients were treated by wide local excision of the tumors for palliation. Two patients were treated with chemotherapy and radiation therapy. Three of the four patients died within 12 months. The authors conclude that diverting colostomy and wide local excision of giant anal cancers offer effective palliation of local wound problems in selected cases.

Adult↗