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Biomedical subjects

A Stanley

Publications and source records attributed to A Stanley.

At least 19 recordsLinked to original sources
PubMed2004

Studies using Teladorsagia circumcincta in an in vitro direct challenge method using abomasal tissue explants.

An in vitro direct challenge (IVDC) method in which abomasal tissue explants maintained at 37 degrees C in Hanks/Hepes solution (pH 7.6) in a high oxygen concentration (incubator gassed with pure oxygen and sealed prior to use) were-challenged with exsheathed third stage larvae of Teladorsagia circumcincta has been used to investigate the tissue association phase of larval establishment. Studies using naïve and recently challenged immune sheep and goat abomasal tissues have shown significant reductions (P < 0.05) in the numbers of tissue associated larvae in material from immune animals. The mechanisms that affect the tissue association process appear to be labile since more larvae were recovered from the tissue digests of previously infected sheep that had not been recently exposed to larval challenge in comparison to those that had been recently challenged (P < 0.05). The method has also been used to demonstrate the influence of protein nutrition on the establishment of larvae in abomasal tissues and region specific differences in the efficacy of exclusion mechanisms. The technique appears to have potential as a means of investigating the crucial first phase of the process of establishment.

Abomasum↗
PubMed2003

A pilot study of adjuvant intraperitoneal 5-fluorouracil using 4% icodextrin as a novel carrier solution.

AIM: This pilot study utilised the sustained intraperitoneal (i.p.) dwell properties of an iso-osmotic solution of 4% icodextrin to investigate the tolerability, toxicity and feasibility of home-based i.p. 5FU adjuvant chemotherapy following resective surgery for colorectal cancer. METHODS: Twenty eligible patients (Dukes' stage B and C with potentially curative resection) underwent perioperative Tenckhoff catheter placement. Ten (6 male, 4 female, aged 46-85; mean 67.5 years) received 5FU chemotherapy. After initial flushing and gradual increase in volumes of 4% icodextrin alone, patients received home-based i.p. 5FU (150-300 mg/m(2)/day given as equal doses at 12-hourly intervals) for 14 days, with a 14-day recovery period, for a maximum of 6 courses. Two incurable patients, treated on compassionate grounds, provided further safety data. RESULTS: Nine of the 10 patients became proficient in self-treatment with 5FU and two completed 6 courses. Frequent abdominal pain was the main dose-limiting toxicity of 5FU, causing withdrawal of three patients after a high (300 mg/m(2)/day) first course and one following a third course at lower doses. I.p. 5FU concentrations (mean>30000 ngml(-1)) were 1000 fold higher than systemic venous levels. Bacterial peritonitis led to two withdrawals but was not a frequent event (microbiologically confirmed incidence of 1 per 27 catheter-months). CONCLUSIONS: Home-based i.p. adjuvant chemotherapy is a feasible treatment option in patients with surgically resected colorectal carcinoma.

Adenocarcinoma↗
PubMed2001

An anterior tibial artery aneurysm in a patient with neurofibromatosis.

Von Recklinghausen's Type 1 neurofibromatosis (NF) is a genetic disorder of neuroectodermal tissue. Arterial involvement has also been recognized. Stenotic lesions predominate, but aneurysms have been documented as well. Aortoiliac, visceral, and cervical aneurysms are well represented in the literature. Rarely noted, however, have been peripheral aneurysms. Typically in more proximal vessels, subclavian, femoral, and popliteal aneurysms have been mentioned. We present the case of a patient with type 1 NF and an anterior tibial artery aneurysm that was subsequently resected. neurofibromatous invasion of the vessel was confirmed by means of pathological tests. We think this is the first reported case of a tibial artery aneurysm associated with NF.

Adult↗
PubMed2001

Senescence and the healing rates of venous ulcers.

OBJECTIVE: Premature cellular senescence has been linked to venous hypertension and may contribute to delayed healing of venous ulcers. We hypothesized that the percentage of senescent cells in in vitro populations of fibroblasts isolated from venous ulcers is directly related to the clinical time-to-healing. METHODS: Biopsy specimens were obtained from ulcer margins and unaffected dermal tissue of the ipsilateral thigh of seven patients with active venous ulcers. Using explant culture techniques, we obtained populations of wound fibroblasts and normal fibroblasts. The percentage of senescence in these cell populations was determined with X-Gal (5-bromo-4-chloro-3-indolyl beta-D-galactoside), which was used as a stain for B-galactosidase, a biomarker for senescent dermal fibroblasts. The X-Gal stain is a peroxidase stain for B-galactosidase. All patients in the study were treated with compression dressings. On a weekly basis, digital images were taken until ulcers healed. Planimetric healing rates were calculated from these images, and an overall time-to-healing was recorded. All cytologic investigations were performed on first passage cells. RESULTS: The average starting ulcer size was 4.2 cm2. Five of the data points represented healed ulcers. The two remaining patients withdrew from the study to pursue other therapies after having been treated with compression dressings for a long time. Linear regression analysis of healed ulcers identified a relationship between percent of senescence and time-to-healing, which was statistically significant (R2 = 0.81, P =.037). High percentages of senescent cells also had a correlation with slowed planimetric healing, which was not statistically significant. CONCLUSIONS: This study demonstrates a clinical correlation between quantitative in vitro senescence and time-to-healing. A percentage of senescence that is greater than 15% in populations of cells isolated from venous ulcers may identify a "difficult to heal" ulcer. There is no good clinical indicator for determining the likelihood of ulcer healing, but these results indicate that senescence percentage may have potential in this regard.

Adult↗
PubMed2000

Cardiac myosin autoantibodies and acute rejection after heart transplantation in patients with dilated cardiomyopathy.

OBJECTIVES: To determine whether humoral autoimmune responses associated with dilated cardiomyopathy (DCM) influence the postoperative clinical course following cardiac transplantation. METHODS: ELISA levels of preformed cardiac myosin (CM) autoantibodies (Abs) in patients with a pretransplant diagnosis of dilated cardiomyopathy (DCM) (n=64) and ischemic heart disease (IHD, n=53) were correlated with cardiac rejection, immunosuppression, and the incidence of endocardial infiltrates after transplantation. RESULTS: Alpha- and beta-CM autoantibody (IgG and IgM) levels were similar in DCM and IHD patients but were statistically higher than in controls. Distribution of preformed (beta-CM) IgM-Abs in patients with and without rejection in the first postoperative year differed in the two groups. DCM patients rejected earlier P=0.006, and the frequency of rejection at 3 months was statistically higher than in IHD patients. Frequency and reactivity of IgM-Abs in DCM patients with rejection [International Society for Heart and Lung Transplant (ISHLT) grade I and above] was 28% compared with 7% in rejection-free patients, P<0.05. IgM-positive patients had a greater frequency and severity of rejection episodes and required more immunosuppression. These patients had rejection earlier than Ab-negative patients, P<0.009. There was no correlation between antibody status and rejection in IHD patients or with IgG in either group. Distribution of IgG subclass differed in the two diseases. DCM patients had significantly higher IgG3 reactivity; 70% of this activity was present in patients who developed moderate rejection. IgG3-positive patients experienced more frequent rejections, as well as a greater incidence of grade 3A/B rejection as the first episode, than did Ab-negative patients (50% vs. 15%), P<0.05. Frequency of endocardial infiltrates was statistically higher in IgG3-positive patients. CONCLUSION: Proinflammatory characteristics of preformed IgG3 and IgM antibodies in DCM patients may influence the frequency and severity of cardiac rejection after transplantation.

Acute Disease↗
PubMed1999

Changing hospitals.

Explore the source record for details and available documents.

Economics, Hospital↗
PubMed1998

Fibroblasts cultured from distal lower extremities in patients with venous reflux display cellular characteristics of senescence.

PURPOSE: Venous reflux precedes the development of venous ulcers. Our earlier work showed that the fibroblasts that are cultured from these wounds display more characteristics of senescence. We evaluated fibroblast senescence in patients with venous reflux but without ulcers to further investigate the role of venous reflux in the predisposition to venous ulcers. METHODS: Fibroblasts that were isolated from skin biopsy specimens of the "gaiter" area (distal) and of the ipsilateral thigh of the same patient (proximal) were compared. Twelve patients with venous reflux (9 patients in clinical, etiologic, anatomic, and pathologic classification 4; 3 patients in classification 5) with an average venous filling index of 5.45 mL/s and 4 patients without venous reflux were enrolled in the study. The growth rates, the response to basic fibroblast growth factor (b-FGF), and the senescence markers (beta-galactosidase activity at a pH level of 6, unstimulated fibroblasts fibronectin protein, and messenger RNA levels) were determined for each cell population. RESULTS: The number of senescence-associated beta-galactosidase positive cells (8.3% +/- 1.9% vs 2.2% +/- 0.8%; P =.008) and the level of cellular fibronectin protein (455.7 +/- 80 vs 210 +/- 51; P =.04) and messenger RNA (16.8 +/- 6.8 vs 13.5 +/- 5.7; P =.042) were significantly higher in the distal fibroblasts as compared with the proximal fibroblast cultures. The growth rates of the distal fibroblasts were lower when compared with the proximal fibroblasts (15,746 +/- 4287 cells/day vs 29,550 +/- 5035 cells/day; P <.002) but were not different in the presence of b-FGF (41,717 +/- 9542 cells/day vs 47,030 +/- 6133 cells/day; P =.53). In the patients without venous reflux, no site differences were noted in the growth rates or the senescence markers between the proximal and distal fibroblasts. CONCLUSION: Distal fibroblasts that are isolated from patients with venous reflux display more senescence characteristics than do proximal fibroblasts and have significantly lower growth rates. Despite senescence, b-FGF restored the distal-fibroblasts growth rate to that of the stimulated proximal fibroblasts, which proposes a therapeutic role for b-FGF. These changes precede ulcer formation and suggest a mechanism that is focal and intrinsically related to venous reflux.

Adult↗
PubMed1998

Fibroblasts cultured from venous ulcers display cellular characteristics of senescence.

PURPOSE: A well-recognized characteristic of venous ulcers is impaired healing. Fibroblasts cultured from venous ulcers (wound-fb) have been shown to have reduced growth rates and are larger than normal fibroblasts (normal-fb) from the ipsilateral limb. Reduced growth capacity and morphologic changes are 2 well-known traits of cellular senescence. Other molecular changes are overexpression of matrix proteins, such as cellular fibronectin (cFN), and enhanced activity of beta-galactosidase at pH of 6.0 (senescence associated beta-Gal, or SA-beta-Gal). Senescence, an irreversible arrest of cell proliferation with maintenance of metabolic functions, may represent in vivo aging and thus may be related to impaired healing. METHODS: Cultured normal-fb and wound-fb from 7 venous ulcer patients (average age, 51 years) were obtained by taking punch biopsies of the perimeter of the ulcer and from the ipsilateral thigh of the same patient. Growth rates, SA-beta-Gal activity, and level of cFN protein (immunoblot) and message (Northern blot) were measured. RESULTS: In all patients, wound-fb growth rates were significantly lower than those of normal-fb (P =.006). A higher percentage of SA-beta-Gal positive cells were found in all wound-fb (average, 6.3% vs. 0.21%; P =.016). The level of cFN, was consistently higher in all wound-fb tested. Also, in 4 patients, the level of cFN messenger RNA (mRNA) was increased. CONCLUSION: Fibroblasts cultured from venous ulcers exhibited characteristics associated with senescent cells. Accumulation of senescent cell in ulcer environment may be associated with impaired healing.

Blotting, Western↗
PubMed1998

Release of the angiogenic cytokine vascular endothelial growth factor (VEGF) from platelets: significance for VEGF measurements and cancer biology.

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor with a key role in several pathological processes, including tumour vascularization. Our preliminary observations indicated higher VEGF concentrations in serum samples than in matched plasma samples. We have now demonstrated that this difference is due to the presence of VEGF within platelets and its release upon their activation during coagulation. In eight healthy volunteers, serum VEGF concentrations ranged from 76 to 854 pg ml(-1) and were significantly higher (P < 0.01) than the matched citrated plasma VEGF concentrations, which ranged from < 9 to 42 pg ml(-1). Using platelet-rich plasma, mean (s.d.) platelet VEGF contents of 0.56 (0.36) pg of VEGF 10(-6) platelets were found. Immunocytochemistry demonstrated the cytoplasmic presence of VEGF within megakaryocytes and other cell types within the bone marrow. From examination of the effects of blood sample processing on circulating VEGF concentrations, it is apparent that for accurate measurements, citrated plasma processed within 1 h of venepuncture should be used. Serum is completely unsuitable. The presence of VEGF within platelets has implications for processes involving platelet and endothelial cell interactions. e.g. wound healing, and in tumour metastasis, when platelets adhering to circulating tumour cells may release VEGF at points of adhesion to endothelium, leading to hyperpermeability and extravasation of cells.

Adult↗
PubMed1997

Ultrasound in the diagnosis and exclusion of intussusception.

Intussusception is a major cause of intestinal obstruction in infancy and childhood. Improved results of treatment have followed the increased use of ultrasound imaging and pneumatic reduction. We prospectively studied the value of ultrasound in both the diagnosis and exclusion of intussusception in a peripheral paediatric unit over a four year period from October 1990 to October 1994. In all, 24 patients had a suspected clinical diagnosis of intussusception of which 19 had typical ultrasound findings. The male to female ratio was 8:11 and age at presentation ranged from 2 to 38 months (mean 11.4 months). There were no false negatives and 2 false positives giving a sensitivity to 100% and specificity of 89%. Thus no intussusception was missed by ultrasound examination. Enema reduction was successful in 76% of cases and factors associated with failure of enema reduction included passage of blood per rectum and symptoms for greater than 24 hours. We conclude that ultrasound should be used as a rapid and sensitive screening procedure in the diagnosis and exclusion.

Child, Preschool↗
PubMed1996

Prolonged intraperitoneal infusion of 5-fluorouracil using a novel carrier solution.

A novel peritoneal carrier solution, Icodextrin 20 (7.5%), has allowed exploration of prolonged, intraperitoneal (i.p.) infusion of the cytotoxic drug 5-fluorouracil (5-FU). A phase I and pharmacokinetic study was performed to determine the toxicities and maximum tolerated dose of prolonged and continuous intraperitoneal 5-FU in patients with peritoneal carcinomatosis. Seventeen patients were entered into this study. Each patient had a Tenckhoff catheter placed into the peritoneal cavity under general anaesthetic. After initial flushing and gradual increase in exchange volumes with Icodextrin 20, 5-FU was administered daily from Monday to Friday, 50% as a bolus in the exchange bag and 50% in an elastomeric infusor device delivering continuous 5-FU to the peritoneal cavity at 2 ml h-1. Treatment was continued for 12 weeks or until intolerable toxicity developed. Abdominal pain and infective peritonitis proved to be the main dose-limiting toxicities. Initial problems with infective peritonitis were overcome by redesign of the delivery system, and it proved possible to deliver 300 mg m-2 5-FU daily (5 days per week) for 12 weeks. Pharmacokinetic studies showed i.p. steady-state 5-FU concentrations (mean 47 500 ng ml-1) that were > 1000-fold higher than systemic venous levels (mean 30 ng ml-1).

Adult↗
PubMed1996

Impact of tobacco-free policy on recruitment and retention of adolescents in residential substance abuse treatment.

As residential treatment programs consider adopting smoke-free policies, treatment providers question whether such policies interfere with patient recruitment and retention. This study assesses the effect of a smoke-free policy on retention using a sample of 155 low-income, mainly minority youth, randomly assigned to two long-term adolescent residential programs at the New Jersey Substance Abuse Treatment Campus. One of these programs has a smoke-free policy, the other does not. Smoking rates are high for the sample. Eighty-five percent of those adolescents smoke, on average half a pack daily, and 39% smoke a pack or more daily. Differential dropout rates between programs for key time periods related to tobacco withdrawal were analyzed to assess the potential effect of smoking policy on retention. Differential dropout rates at the point of program assignment, in the first two days of residency (p = .43), and for the first two weeks of residency (p = .37) show no differences between programs. While analyses showed heavy smokers are more likely than others to leave treatment early, they were likely to leave from either program regardless of smoking policy. As well, verbal expressions of dissatisfaction with smoking policy did not result in drop outs. These results indicate that smoke-free policies have no detrimental effect on program retention.

Adolescent↗
PubMed1996

Covert speech behavior during a silent language recitation task.

This study tested the prediction that covert speech behavior measured electromyographically from the lips is significantly more prominent during a brief silent-language recitation task than a brief nonlanguage visualization task. Subjects were 20 right-handed, adult volunteers who agreed to participate. Subjects were tested in a multiple-baseline reversal design following an ABAB procedure whereby A1 and A2 were 30-sec. rest periods. B1 and B2 were alternatively assigned 30-sec. silent-language recitation and visualization test periods, respectively. Subjects' dorsal lips and nondominant forearm EMG measures were taken during resting baseline and testing conditions. In addition, subjects' skin surface temperature and heartrate were measured during the rest and test conditions. For the silent-language task, subjects were asked to recite 'mentally' the Pledge of Allegiance to the flag. Subjects were instructed to 'imagine seeing' the American flag for the visualization task. Subjects' mean lip EMG activity increased significantly from rest to the silent-language recitation task, while no significant change in mean lip EMG was observed from rest to the visualization condition.

Adult↗
PubMed1996

Specific effect of vincristine on epididymis.

Wistar strain male albino rats were administered with vincristine (VCR) sulphate (10 micrograms/day for 15 days); epithelial cell types of the caput (zone II) and cauda (zone V) were studied light microscopically adopting semithin sectioning. VCR caused conspicuous pathological changes in the principal and apical cells of the caput and the clear cells of the cauda. The study points to toxic effect of VCR on these cell types, suggesting impairment of epididymal function, particularly concerning sperm maturation and endocytotic removal of the contents of the cytoplasmic droplets and dead sperm.

Animals↗