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Biomedical subjects

A Stanley

Publications and source records attributed to A Stanley.

At least 19 recordsLinked to original sources

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↗

Changing hospitals.

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Economics, Hospital↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

The effects of deinstitutionalization on adults with learning disabilities.

We compared a group of people with learning disabilities who have been deinstitutionalized with a control group remaining in an institution on measures of adaptive and maladaptive behaviour, community living skills, social skills, and quality of life. In general, there was no change over 30 months for the control group. Changes for the experimental group were either not seen or were generally modest in scale, and tended to occur within 6 months of moving, the measures staying relatively stable thereafter. Implications for detailed examination of the effects of deinstitutionalization were discussed.

Activities of Daily Living↗

Dentistry--the dependence upon medicine and surgery for its professional status.

As a profession, dentistry was set on its course in 1858. We are still living with the consequences of the 1858 Medical Act, which placed dentists under the authority of the general surgeons. Our history is more complex than just evolution from the barber surgeon. This essay traces the development of the profession of dentistry and makes a comment about its future autonomy.

History of Dentistry↗

A phase I/II trial of recombinant human granulocyte-macrophage colony-stimulating factor in the intensification of cisplatin and cyclophosphamide chemotherapy for advanced ovarian cancer.

A pilot study was undertaken in eight patients to assess the feasibility of recombinant human granulocyte-macrophage colony-stimulating factor (rH GM-CSF) support to intensify standard chemotherapy for advanced ovarian cancer using a shortened 15 day treatment interval. Only four patients completed the course of six cycles of cisplatin 75 mg m-2 and cyclophosphamide 750 mg m-2 with rH GM-CSF, 3-5 micrograms kg-1 day-1, days 3-14, but one of these suffered a toxic death on study. Another died of disease progression. There were two episodes of life-threatening infection (WHO grade 4), and three patients were withdrawn because of various rH GM-CSF-related problems. Although potentially affording some patients the hypothetical benefits of dose intensification, as well as the possible attraction of a shorter duration of chemotherapy, this regimen is not without problems.

Adenocarcinoma↗

Anabolic steroids--the drugs that give and take away manhood. A case with an unusual physical sign.

A case is presented in which the abuse of anabolic steroids by a body builder led to an unusual physical sign. The case discusses the effects that anabolic steroid abuse can have upon manhood. The frequency of anabolic steroid misuse is increasing. The implications of this with respect to psychiatric illness and violent crime are discussed. It is well known that the use of anabolic steroids among young men, body builders in particular, is growing apace (Perry and Littlepage, 1992), and they may be aware of the risks of impurity and contamination. There is a wide range of anabolic steroids in use; they are often used in doses of greater than 1 mg/kg per day. As well as single use, the misuser may 'stack' (use more than one at a time) or 'pyramid' (use increasing doses of a given drug) the steroids (Kennedy, 1990). The physical and psychiatric effects of anabolic steroids are well known (Kashkin and Kleber, 1989; Brower, 1992; Pope and Katz, 1988). However, we describe a case with psychiatric symptoms, a violent outburst and a unique (?) physical sign.

Adult↗

Ultrastructural changes in the Leydig cell on treatment with vincristine.

The effect of vincristine (VCR), an anticancer drug which brings about mitotic arrest by disturbing the microtubules of the spindle fibres, on the Leydig cells was investigated adopting ultrastructural and RIA of hormone techniques. The Leydig cells of VCR treated rats were necrotic and oedematous with severe damage caused to the steroidogenic machinery, viz the mitochondria and smooth endoplasmic reticulum. Such damage was duly reflected in the serum levels of hormones, wherein the androgen level was decreased with compensatory hypersecretion of follicle-stimulating hormone and luteinizing hormone. The results strongly implicate VCR in Leydig cell toxicity, and explain the problems in the reproductive performance faced by cancer patients receiving VCR as one of the drugs, both during treatment and after remission.

Animals↗