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Biomedical subjects

J Holland

Publications and source records attributed to J Holland.

At least 55 records · Page 3Linked to original sources

Epidemiology of vancomycin usage at a children's hospital, 1993 through 1995.

OBJECTIVE: To describe the epidemiology of vancomycin usage at a children's hospital. METHODS: A cohort study of patients at Egleston Children's Hospital who were charged for the receipt of vancomycin from October, 1992, through October, 1995, was performed. Data were obtained from pharmacy charge records in the hospital's medical records information system. RESULTS: During the study period there were 3589 patient hospitalizations in which vancomycin was used. Patients receiving vancomycin were predominantly male (56.6%) and white (62.4%), ranged in age from 0 to 31 (median, 3.8) years and had an average length of stay of 6.0 days. The total number of vancomycin doses was 105,704; the median number of vancomycin doses during each patient hospitalization was 11.0 (range, 1 to 1215). The total charge for vancomycin used was $2,009,746; the median charge for vancomycin per patient was $297.50 (range, $11 to 19,864). The majority (75.7%) of vancomycin doses were given on the hematology (27.6%), neurosurgery (17.9%), cardiothoracic surgery (13.4%), neonatology (9.7%) or general pediatrics (7.1%) services. Overall surgery service patients were significantly more likely to receive vancomycin than were medicine service patients (1267 doses/6221 admissions vs. 1954/19,446; relative risk, 2.03; P < 0.001). During the study period the number of vancomycin doses decreased significantly (P < 0.001). CONCLUSIONS: This study shows the value of evaluating antimicrobial use through a pharmacy database. Although vancomycin use decreased during the study period, large amounts of vancomycin are still being prescribed primarily on subspecialty service patients. Interventions to reduce vancomycin use should focus on these groups.

Adolescent↗

Emerging zygomycoses of humans: Saksenaea vasiformis and Apophysomyces elegans.

Since the first isolation of Saksenaea vasiformis and Apophysomyces elegans from soil specimens in 1953 and 1979, respectively, more than 30 human infections have occurred with these organisms. This paper will review the laboratory diagnosis and clinical manifestations of infections with these emerging zygomycetes.

Humans↗

A pilot survey of sexual function and quality of life following 3D conformal radiotherapy for clinically localized prostate cancer.

PURPOSE: To assess the impact of high dose three-dimensional conformal radiotherapy (3D CRT) for prostate cancer on the sexual function-related quality of life of patients and their partners. METHODS AND MATERIALS: Sixty of 124 consecutive patients (median age 72.3 years) treated with 3D CRT for localized prostate cancer were surveyed and reported being potent prior to treatment. The answers to survey questions assessing the impact of quality of life related to sexual function from these 60 patients and their partners forms the basis for this retrospective analysis. RESULTS: Following 3D CRT, 37 of 60 patients (62%) retained sexual function sufficient for intercourse. Intercourse at least once per month was reduced from 71 to 40%, whereas intercourse less than once per year increased from 12 to 35%. Following treatment, 25% of patients reported that the change in sexual dysfunction negatively affected their relationship or resulted in poor self-esteem. This outcome was associated with impotence following treatment (p < 0.01). Patients who had partners and satisfactory sexual function appeared to be at a higher risk of having a negatively affected relationship or losing self-esteem if they become impotent (p < 0.05). Partners of patients who reported a negatively affected relationship or loss of self-esteem appear to be less likely to return the survey instrument used (p = 0.02). CONCLUSIONS: More work is needed to evaluate the impact of radiotherapy and other treatments on the quality of life of patients and their partners to allow adequate informed consent to be given.

Adenocarcinoma↗

Prostate volumes defined by magnetic resonance imaging and computerized tomographic scans for three-dimensional conformal radiotherapy.

PURPOSE: To compare the prostate volumes defined on magnetic resonance imaging (MRI), and noncontrast computerized tomographic (CT) scans used for three-dimensional (3D) treatment planning. METHODS AND MATERIALS: Ten patients were simulated for treatment using immobilization and a retrograde urethrogram. 3D images were used to compare prostate volumes defined by MRI (4-6 mm thick slices) and CT images (5 mm thick slices). Prostate volumes were calculated in cm(3) using the Scanditronix 3D planning system. MRI/CT images were merged using bony anatomy to define the regions of discrepancy in prostate volumes. RESULTS: The mean prostate volume was 32% larger (range-5-63%) when defined by noncontrast CT compared to MRI. The areas of nonagreement tended to occur in four distinct regions of discrepancy: (a) the posterior portion of the prostate, (b) the posterior-inferior-apical portion of the prostate, (c) the apex due to disagreement between a urethrogram based definition and the location defined by MRI, (d) regions corresponding to the neurovascular bundle. CONCLUSION: There is a tendency to overestimate the prostate volume by noncontrast CT compared to MRI. Awareness of this tendency should allow us to be to more accurately define the prostate during 3-D treatment planning.

Humans↗

Flutamide-induced liver toxicity including fatal hepatic necrosis.

PURPOSE: To describe hepatic injuries in three patients who received flutamide prior to and during radiation treatment to make radiation oncologists aware of the need for careful monitoring of liver function during use of this drug. METHODS AND MATERIALS: The records of three patients who developed abnormal liver function tests while undergoing total androgen suppression (TAS), as well as the literature concerning flutamide toxicity were reviewed and summarized. RESULTS: Three of 34 patients treated with a TAS regimen incorporating flutamide developed significant hepatic abnormalities: elevated transaminases [2] and fatal hepatic necrosis [1]. Following the discontinuation of flutamide, two patients recovered fully. Unfortunately, the third patient's hepatic function continued to deteriorate, which culminated in his death. Transient elevations in serum transaminases, which do not exceed four times the upper limits of normal, are common and apparently without clinical significance. Unfortunately, idiosyncratic serious and/or fatal liver damage can occur. Significant liver toxicity may be obviated by monitoring of liver function tests (LFT) early in the course of flutamide therapy. CONCLUSION: The incidence of hepatic toxicity associated with flutamide may be higher than previously suggested. To prevent the development of serious hepatic dysfunction, all patients receiving flutamide should be monitored clinically for signs and symptoms referable to hepatic injury and with serial LFT. We recommend baseline LFT followed by serial LFT at weeks 2, 4, 6, and 8 from the start of treatment with flutamide. Flutamide should be stopped promptly if significant liver abnormalities are detected.

Adenocarcinoma↗

Culture of human vascular endothelial cells on an RGD-containing synthetic peptide attached to a starch-coated polystyrene surface: comparison with fibronectin-coated tissue grade polystyrene.

A synthetic peptide, Gly-Arg-Gly-Asp-Ser-Pro-Lys (GRGDSPK), which includes the cell-adhesive region of fibronectin, Arg-Gly-Asp (RGD), was covalently bound to a dialdehyde starch (DAS) coating on a polymer surface by reductive amination. The GRGDSPK/DAS-coated surface was characterized by atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). AFM and SEM revealed a uniform, roughened, textured surface, much more so than standard polymer or adhesive protein-coated polymer surfaces. XPS showed that GRGDSPK binding to DAS occurred in dose-dependent fashion in the 0-200 micrograms ml-1 GRGDSPK concentration range, with a plateau happening in the 200-400 micrograms ml-1 range. AFM revealed a uniform peptide layer on the DAS surface with a maximum separation distance of 50 nm between peptides. Angle-dependent XPS showed that the peptide is present in nearly constant amounts to at least 10 nm depth of the DAS coating. The attachment, spreading and growth properties of anchorage-dependent human umbilical vein endothelial cells (EC) on the GRGDSPK/DAS-coated polystyrene surface were compared with a standard fibronectin-coated polystyrene surface. EC adhesion, spreading and growth properties were similar for cells plated on polystyrene surfaces coated with fibronectin (5 micrograms cm-2) and GRGDSPK (25-50 micrograms ml-1)/DAS. In contrast, EC adhesion, spreading and growth performance significantly increased for cells plated on GRGDSPK (100-200 micrograms ml-1)/DAS compared with the fibronectin-coated surface. These findings support the conclusion that the GRGDSPK/DAS-coated surface can be substituted for an adhesive protein-coated surface in the culture of anchorage-dependent cells.

Amino Acid Sequence↗

Conservation and antigenic cross-reactivity of the transferrin-binding proteins of Haemophilus influenzae, Actinobacillus pleuropneumoniae and Neisseria meningitidis.

Haemophilus influenzae acquires iron from the iron-transporting glycoprotein transferrin via a receptor-mediated process. This involves two outer-membrane transferrin-binding proteins (Tbps) termed Tbp1 and Tbp2 which show considerable preference for the human form of transferrin. Since the Tbps are attracting considerable attention as potential vaccine components, we used transferrin affinity chromatography to examine their conservation amongst 28 H. influenzae type b strains belonging to different outer-membrane-protein subtypes as well as six non-typable strains. Whole cells of all type b and non-typable strains examined bound human transferrin; whilst most strains possessed a Tbp1 of approximately 105 kDa, the molecular mass of Tbp2 varied from 79 to 94 kDa. Antisera raised against affinity-purified native H. influenzae Tbp1/Tbp2 receptor complex cross-reacted on Western blots with the respective Tbps of all the Haemophilus strains examined. When used to probe Neisseria meningitidis Tbps, sera from each of four mice immunized with the Haemophilus Tbp1/2 complex recognized the 68 kDa Tbp2 of N. meningitidis strain B16B6 but not the 78 kDa Tbp2 of N. meningitidis strain 70942. Serum from one mouse also reacted weakly with Tbp1 of strain B16B6. Apart from a weak reaction with the Tbp2 of a serotype 5 strain, this mouse antiserum failed to recognize the Tbps of the porcine pathogen A. pleuropneumoniae. However, a monospecific polyclonal antiserum raised against the denatured Tbp2 of Neisseria meningitidis B16B6 recognized the Tbps of all Haemophilus and Actinobacillus strains examined. Since H. influenzae forms part of the natural flora of the upper respiratory tract, human sera were screened for the presence of antibodies to the Tbps. Sera from healthy adults contained antibodies which recognized both Tbp1 and Tbp2 from H. influenzae but not N. meningitidis. Convalescent sera from meningococcal meningitis patients contained antibodies which, on Western blots, recognized the Tbps2s of both pathogens. These data demonstrate the existence of shared epitopes on the Tbps of H. influenzae, N. meningitidis and A. pleuropneumoniae despite their transferrin species specificity.

Actinobacillus pleuropneumoniae↗

The role of estradiol, progesterone, and transforming growth factor on human endometrioma cell culture.

The present study demonstrates several aspects of endometrioma cells in culture, namely, 1) cell growth, proliferation, and morphology, 2) effect of cell culture on estrogen and progesterone receptor concentration, 3) effect of estradiol, progesterone, and transforming growth factor. The tissue sample was obtained from ovarian endometriomas that were removed via laparotomy or laparoscopy. The tissue sample was digested with collagenase. After washing, the tissue was cultured in endothelial cell culture medium. Cell count was done by flow cytometry. Receptor study was done by immunohistochemistry. The results demonstrated the growth and proliferation of endometrioma cell in culture medium. Electron microscopy showed stroma-like cells. The cells lost their estrogen and progesterone receptors. Estradiol and progesterone added to these cultures did not affect the rate of growth and proliferation of the cells. Transforming growth factor significantly increased the rate of growth and proliferation of these cells.

Cell Division↗

Particle uptake and translocation across epithelial membranes.

Oral delivery of drugs and vaccines has many advantages over other routes of administration. For example, for vaccination, enteric delivery may result in the induction of a mucosal immune response against pathogens which colonise and invade the mucosa. However, the oral delivery of peptide or protein drugs or antigens is beset with problems, such as gastrointestinal breakdown of labile molecules, low level of macromolecular absorption and, for vaccines, the poor immune response usually elicited by orally administered soluble antigens. Investigations are therefore in progress to develop means of increasing intestinal absorption and decreasing digestion of orally administered molecules. Molecules can be incorporated into biodegradable microparticles to reduce the effect of gut secretions and to enable the absorption of bioactive agents in an unaltered form. The uptake of microparticulates through the gut wall is accepted as a true biological phenomenon but the mechanism and route of uptake have not been established. Furthermore, in general, only small numbers of microparticles are translocated across epithelial membranes, possibly making these systems inappropriate for drug or vaccine delivery. This paper reviews particle uptake across the gastrointestinal tract and describes studies carried out to determine whether a humoral response can be elicited following oral administration of an antigen associated with biodegradable poly(DL lactide-coglycolide) microparticles. The use of lipid delivery vehicles to enhance microparticle uptake and the selective transport of microspheres across M cells is also described.

Administration, Oral↗

Liposomal cyclosporine. Characterization of drug incorporation and interbilayer exchange.

A number of previous studies have examined the application of liposomes as carriers for the immunosuppressive agent cyclosporine. These studies, however, have generated equivocal results, particularly with regard to the therapeutic properties of such systems. In the present work, we have characterized cyclosporine incorporation into well defined liposomes, large unilamellar vesicles, and have examined the stability of drug association. Contrary to some earlier reports, we show that only modest levels of cyclosporine can be accommodated in the liposomal membrane and that the extent of drug incorporation is greatly reduced as the bilayer cholesterol content is increased. Furthermore, we demonstrate that cyclosporine, despite its hydrophobic character, can rapidly exchange between vesicles. This raises the possibility that, after i.v. administration, drug migration to other blood components might negate the potential benefits arising from liposomal delivery. In a companion paper, therefore (Choice et al., Transplantation, 1995, this issue), we have followed the pharmacokinetics and biodistribution of liposomal cyclosporine in a study that examined the behavior of both the drug and the liposomal carrier.

Cholesterol↗

Potency following high-dose three-dimensional conformal radiotherapy and the impact of prior major urologic surgical procedures in patients treated for prostate cancer.

PURPOSE: To assess the impact of high-dose three-dimensional conformal radiotherapy (3DCRT) on potency in patients treated for clinically localized prostate cancer and to identify factors that might predict the outcome of sexual function following treatment. METHODS AND MATERIALS: One hundred twenty-four consecutive patients treated with 3DCRT for localized prostate cancer at UCSF between 1991-1993 were included in this retrospective analysis. Patient responses were obtained from a mailed questionnaire, telephone interviews, or departmental records. Medial follow-up was 21 months. RESULTS: Sixty patients reported having sexual function prior to 3DCRT, including 47 who were fully potent and 13 who were marginally potent. Of the remaining 64 patients, 45 were impotent, 7 were on hormones, 1 was status-postorchiectomy, and 11 were not evaluable. Following 3DCRT, 37 of 60 patients (62%) retained sexual function sufficient for intercourse. Of those with sexual function before irradiation, 33 of 47 (70%) of patients fully potent and 4 of 13 (31%) of patients marginally potent maintained function sufficient for intercourse (p < 0.01). Potency was retained in 6 of 15 (40%) patients with a history of a major urologic surgical procedure (MUSP) and in 31 of 45 (69%) with no history of a MUSP (p < 0.04). Transurethral resection of the prostate was the MUSP in eight of these patients, with four (50%) maintaining sexual function. CONCLUSIONS: Patients who receive definitive 3DCRT for localized prostate cancer appear to maintain potency similar to patients treated with conventional radiotherapy. However, patients who are marginally potent at presentation or who have a history of a MUSP appear to be at increased risk of impotence following 3DCRT.

Aged↗

Sexual health education interventions for young people: a methodological review.

OBJECTIVES: To locate reports of sexual health education interventions for young people, assess the methodological quality of evaluations, identify the subgroup with a methodologically sound design, and assess the evidence with respect to the effectiveness of different approaches to promoting young people's sexual health. DESIGN: Survey of reports in English by means of electronic databases and hand searches for relevant studies conducted in the developed world since 1982. Papers were reviewed for eight methodological qualities. The evidence on effectiveness generated by studies meeting four core criteria was assessed. Judgments on effectiveness by reviewers and authors were compared. PAPERS: 270 papers reporting sexual health interventions. MAIN OUTCOME MEASURE: The methodological quality of evaluations. RESULTS: 73 reports of evaluations of sexual health interventions examining the effectiveness of these interventions in changing knowledge, attitudes, or behavioural outcomes were identified, of which 65 were separate outcome evaluations. Of these studies, 45 (69%) lacked random control groups, 44 (68%) failed to present preintervention and 38 (59%) postintervention data, and 26 (40%) omitted to discuss the relevance of loss of data caused by drop outs. Only 12 (18%) of the 65 outcome evaluations were judged to be methodologically sound. Academic reviewers were more likely than authors to judge studies as unclear because of design faults. Only two of the sound evaluations recorded interventions which were effective in showing an impact on young people's sexual behaviour. CONCLUSIONS: The design of evaluations in sexual health intervention needs to be improved so that reliable evidence of the effectiveness of different approaches to promoting young people's sexual health may be generated.

Adolescent↗

Effect of starch-containing glove powder on wound healing in the rat.

The effect of the starch-containing powder BioSorb on wound healing was examined in an immunocompetent and a T cell-deficient animal model. Wounds were tested by tensionometry to give values of resilience, ultimate strength, toughness and extension. Starch significantly decreased the resilience (P < 0.03), ultimate strength (P < 0.004), and toughness (P < 0.006) of wounds in the immunocompetent model but was not shown to affect the healing of wounds in T cell-depleted animals. When the uncontaminated wounds of the two groups were compared, those from T cell-depleted animals were tougher (P < 0.04) and less extensile (P < 0.0002). These results suggest that starch impairs wound healing by its effect on the T cell-mediated immune system, and that this system may also be involved in regulation of the reparative process because its absence leads to tougher wounds.

Animals↗