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Biomedical subjects

P Davis

Publications and source records attributed to P Davis.

At least 235 records · Page 13Linked to original sources
PubMed1994

Dose-intense taxol: high response rate in patients with platinum-resistant recurrent ovarian cancer.

BACKGROUND: Paclitaxel (Taxol), a diterpene plant product that promotes tubulin polymerization, has documented activity against a number of solid tumors, including ovarian cancer and breast cancer. PURPOSE: Our purpose was to conduct a phase II clinical trial investigating the response of patients with advanced recurrent ovarian carcinoma to high-dose paclitaxel combined with granulocyte colony-stimulating factor (G-CSF). METHODS: A prospective phase II clinical trial of patients with advanced-stage, recurrent ovarian cancer was undertaken. Patients received 250 mg/m2 paclitaxel every 21 days; cycles were given on a rigid schedule; delays were permitted only for extreme circumstances. G-CSF at a dose of 10 micrograms/kg per day was given to ameliorate myelo-suppression. If a patient showed fever and neutropenia, G-CSF dosage was increased to 20 micrograms/kg per day so that paclitaxel dose intensity could be maintained. Patients were assessed for response every two cycles, and those with complete radiographic resolution of disease underwent peritoneoscopy. RESULTS: Forty-four patients were assessable for response. Twenty-one had a reduction in tumor volume greater than 50%, yielding an objective response rate of 48% (21 of 44 patients; 95% confidence interval, 32%-63%). Six (14%) of the 44 patients had complete radiographic resolution of disease; two of the six also had negative biopsy specimens and washings at peritoneoscopy. Age, number of prior regimens, and clinical platinum resistance did not influence response rate or ability to maintain dose intensity. Dose intensity was maintained at the targeted level for up to 14 consecutive cycles of therapy. CONCLUSIONS: We observed a 48% response rate with dose-intense paclitaxel for patients with advanced-stage, platinum-resistant, recurrent ovarian cancer. The response rate is higher than previously reported for paclitaxel at a lower dose in similar cohorts of patients treated without G-CSF. Comparison of phase II studies of paclitaxel suggests a dose-response relationship. Therapy with dose-intense paclitaxel and G-CSF should be considered for patients with advanced, platinum-refractory ovarian cancer.

Adult↗
PubMed1994

Hematologic disposition of hydroxychloroquine enantiomers.

Hydroxychloroquine (HCQ) is a racemic antiarthritic agent that has a long half-life (t1/2) in plasma and accumulates in blood cells. To study the relationships between HCQ concentrations in plasma, serum, and whole blood and to determine the optimal blood fraction to use for therapeutic drug monitoring of the drug, we studied the relative distribution of the HCQ enantiomers in various fractions of human blood under in vivo and in vitro conditions. Substantially greater concentrations of both enantiomers were found in serum as compared with plasma because of release via platelet activation. After in vitro incubations of the separated blood cells with HCQ, high concentrations of both enantiomers were found in leukocytes, and low concentrations in erythrocytes and platelets; the R:S ratio in vitro was near unity in all of the cells examined. Unlike the in vitro cellular uptake, the concentrations of HCQ in vivo were significantly lower and stereoselective (R:S ratio = 2). There was almost no drug in the polymorphonuclear cells (PMN) in vivo, despite a substantial uptake in vitro after incubation of separated cells. The enantiomeric (R:S) ratio in the urinary excretion of the enantiomers was significantly correlated with that in plasma. The plasma-protein binding of the enantiomers was stereoselective and complimented the cellular uptake findings; the unbound fraction was dependent on the plasma concentrations of alpha 1-acid glycoprotein, but not albumin. Although concentrations in whole blood correlated well with those in lymphocytes and monocytes (the proposed site of HCQ action), stronger correlations were found between concentrations in serum and in the mononuclear cells.

Adult↗
PubMed1994

Evaluation of a rheumatoid arthritis patient education program: impact on knowledge and self-efficacy.

We have evaluated the effects of an education program on the knowledge and self-efficacy of 51 rheumatoid arthritis patients, using two previously validated questionnaires. At completion of the program, both knowledge and self-efficacy were significantly improved and this was maintained at follow-up. However, there was no correlation between knowledge and self-efficacy at baseline and follow-up, suggesting that these variables improved independently of each other. We conclude that education programs are a worthwhile means of improving the non-medical causes of morbidity in rheumatoid arthritis patients and that the two instruments utilized are a valuable means of both demonstrating effectiveness and quality assurance.

Arthritis, Rheumatoid↗
PubMed1994

Adolescents and colposcopy: the use of different procedures to reduce anxiety.

OBJECTIVE: Two consecutively occurring studies examined whether using a video colposcope to view this procedure or allowing the female adolescent to watch music videos would reduce anxiety and related body movements. STUDY DESIGN: Female adolescents who underwent colposcopy were randomly assigned to one of two groups, experimental and control. In study 1, 27 female adolescents were randomly assigned either to view the procedure on a television monitor or to be part of a control group (no visual distraction). In study 2, 30 female adolescents were randomly assigned either to a music video group or to a control group. Studies were completed in a consecutive manner and used the same measures, colposcopic equipment, and professional staff, including physician. Multiple measures of anxiety were used (heart rate, behavior observation, and paper and pencil) before, during, and after the procedure. During each colposcopy the subject's behavior across 10 dimensions was observed and coded. Data were analyzed by chi 2, analysis of variance, and Student t tests. RESULTS: Study 1 found no significant differences in body movements and anxiety ratings between the video colposcope group and controls. In study 2, subjects who were allowed to watch the music videos demonstrated significantly fewer body movements indicative of pain, required less physician reassurance, and received fewer procedural explanations (p < 0.05). CONCLUSION: Results suggest that allowing a female adolescent to watch music videos during a colposcopic examination appears to decrease body movements associated with discomfort.

Adolescent↗
PubMed1994

Rheumatic diseases in African blacks.

Contrary to previous belief, there is increasing evidence that a broad spectrum of rheumatic diseases do affect African blacks. Although properly conducted epidemiological studies have yet to be performed, reports of population surveys from a variety of sub-Saharan African countries indicate that diseases such as rheumatoid arthritis (RA), gout, and the connective tissue diseases are observed, although some differences in clinical presentation may occur as a result of cultural, racial, and socioeconomic factors. Rheumatoid arthritis is common in some parts of Africa and less common in others. In particular, a significantly lower prevalence of RA in rural areas compared with urban cohorts has led to the hypothesis that environmental factors associated with urbanization may be involved in disease pathogenesis. A similar hypothesis has been suggested for hyperuricemia and gout. Clinical features of disease may also be different in Africans when compared with other population subgroups such as with systemic lupus erythematosus although this may be artefactual as different accessibility to health care and referral practices may result in only the more severe cases coming to medical attention (eg, lupus nephritis). Immunogenetic factors may reduce the prevalence of some conditions such as the spondyloarthropathies. Although the association between HLA-DR4 and RA holds true in Africans, the same is not so for the association of HLA-B27 with ankylosing spondylitis (AS). The prevalence of HLA-B27 in African blacks is 10 times less than Caucasian populations, in part accounting for the low prevalence of spondyloarthropathies, although its association with AS is low. Other conditions such as human immunodeficiency virus (HIV)-related arthropathies appear to be an increasing medical problem. The panepidemic of acquired immunodeficiency syndrome in Africa has resulted in an increased awareness of the different types of arthritis that may be associated with HIV. These are similar to those reported in other parts of the world, although risk factors are different in Africa where heterosexual transmission is a more common cause than homosexual transmission or i.v. drug usage. Information on other rheumatic diseases such as osteoarthritis and soft tissue rheumatism are slowly emerging. Rheumatic manifestations of the infectious diseases, which are endemic in Africa, remain a uniquely fascinating aspect of rheumatology practice on the African continent. Therefore, African countries will increasingly be a continued valuable source of clinical material for comparative studies to help elucidate factors that influence the development of rheumatic diseases.

Africa↗
PubMed1994

Prevalence of selected autoantibodies in different elderly subpopulations.

We have evaluated the prevalence of selected autoantibodies commonly utilized in rheumatologic practice in different elderly subpopulations grouped according to their clinical status. RF, ANA, double-stranded DNA antibodies, and antibodies to extractable nuclear antigens (ENA) were measured in the serum of all participants using standardized laboratory assays. One hundred and fifty-nine elderly subjects were enrolled, of whom 63 were classified as successfully aging elderly, 62 were ambulatory chronically ill residents of a nursing or Veterans home and 34 were patients attending an RA clinic. Prevalence of autoantibodies were compared to healthy adult blood donors. There was no statistically significant increase in autoantibodies in successfully aging elderly compared to healthy young controls. RF, ANA and ENA antibodies were significantly increased in only the chronically ill and RA sufferers. Antibodies to nDNA were absent in all groups. We conclude that autoantibodies commonly utilized in rheumatological practice are not globally non-specifically increased as a result of aging, but increase in prevalence in chronically ill elderly. Therefore assessment of health status is necessary to evaluate the clinical significance of these autoantibodies in the elderly.

Aged↗
PubMed1994

Stroke in women.

Morbidity and mortality rates for stroke are higher in men than women with the exception of subarachnoid hemorrhage. Temporal trends are similar in the two sexes with a slowdown in the decline in mortality rates and a leveling or increase in morbidity rates. Women are more likely than men to have cervical bruits but less likely to have carotid stenosis on ultrasonography. Some factors associated with stroke are unique to women: pregnancy, use of oral contraceptives, postmenopausal hormonal replacement, and choriocarcinoma. Postmenopausal hormonal use is associated with a decreased risk of stroke in observational studies but clinical trials are needed. Control of hypertension and cessation of smoking to reduce the risk of stroke is equally effective in both sexes. Aspirin and ticlopidine are effective in secondary prevention of stroke in women, whereas women may be more sensitive to warfarin than men.

Adolescent↗
PubMed1994

Delta opioid receptor selective ligands; DPLPE-deltorphin chimeric peptide analogues.

Further efforts to correlate the topography of the bioactive structures of DPDPE and the deltorphins, two delta-opioid receptor active peptide families, are reported. A number of DPLPE-deltorphin chimeric peptides have been synthesized in which the C-terminal dipeptide delta-address of the deltorphins (-Val-GlyNH2, -Nle-GlyNH2) have been linked to the highly delta-opioid selective cyclic peptides DPDPE or DPLPE. These studies demonstrate that a major structural feature determining high potency of hybrid analogues is the chirality of the amino acid residue in position 5. The radioligand binding assays have revealed a decrease in potency (compared to DPDPE) at delta-receptors when the C-terminal dipeptides were added to DPDPE. On the other hand, chimeric peptides of DPLPE with these same C-terminal dipeptides retained high delta-selectivity and affinity. Similar results were obtained using the mouse vas deferens (MVD) and guinea pig ileum (GPI) bioassays. The importance of the hydrophilicity of amino acids in positions 2 and 5 for delta-selectivity is consistent with the previous finding for DPLPE and DPDPE. On the other hand, the replacement of phenylalanine-4 with p-chlorophenylalanine-4 did not increase delta-selectivity as in DPDPE. These findings suggest that the delta-receptor interacts with hybridized enkephalins and deltorphins somewhat differently than with DPDPE.

Amino Acid Sequence↗
PubMed1994

Proteinuria in passive Heymann nephritis is associated with lipid peroxidation and formation of adducts on type IV collagen.

Passive Heymann nephritis (PHN) is a model of human membranous nephropathy that is characterized by formation of granular subepithelial immune deposits in the glomerular capillary wall which results in complement activation. This is causally related to damage of the filtration barrier and subsequent proteinuria. The local accumulation of injurious reactive oxygen species (ROS) is a major effector mechanism in PHN. ROS may induce tissue damage by initiating lipid peroxidation (LPO). In turn, this leads to adduct formation between breakdown products of LPO with structural proteins, such as formation of malondialdehyde (MDA) or 4-hydroxynonenal-lysine adducts. To examine the role of LPO in the development of proteinuria we have localized MDA and 4-hydroxynonenal-lysine adducts in glomeruli of PHN rats by immunofluorescence microscopy, using specific monoclonal antibodies. By immunogold electron microscopy, MDA adducts were localized to cytoplasmic vesicles and cell membranes of glomerular epithelial cells, to the glomerular basement membrane (GBM), and also to immune deposits. Type IV collagen was specifically identified as being modified by MDA adducts, using a variety of techniques. Collagenase pretreatment of GBM extracts indicated that the NC-1 domain of type IV collagen was a site of adduct formation. When LPO was inhibited by pretreatment of PHN rats with the antioxidant probucol, proteinuria was reduced by approximately 85%, and glomerular immunostaining for dialdehyde adducts was markedly reduced, even though the formation of immune deposits was not affected. By contrast, lowering of the serum cholesterol levels had no influence on the development of proteinuria. These findings are consistent with the premise that ROS-induced glomerular injury in PHN involves LPO and that this results not only in damage of cell membranes but in modification of type IV collagen in the GBM as well. The close temporal correlation of the occurrence of LPO with proteinuria and the ability of probucol to inhibit proteinuria support a causal role for LPO in the the alteration of the glomerular permselectivity which results in proteinuria.

Aldehydes↗
PubMed1994

Transforming growth factor beta 1 can induce CIP1/WAF1 expression independent of the p53 pathway in ovarian cancer cells.

Transforming growth factor beta (TGF beta) is an important regulator of cellular proliferation. In normal ovarian epithelial cells, TGF beta acts to inhibit growth. However, in ovarian cancer cell lines, this effect is usually lost. Although the regulatory pathway of TGF beta remains unclear, TGF beta-treated cells arrest late in G1. This inhibition appears to involve blocking of the cyclin-dependent kinase phosphorylation of the retinoblastoma protein. Recently, a general inhibitor of cyclin-dependent kinases, CIP1/WAF1/p21, was identified. Expression of CIP1 is positively regulated by binding of wild-type p53 to a consensus response element upstream of the CIP1 gene. Overexpression of the CIP1 protein causes growth suppression, analogous to TGF beta and wild-type p53. We have examined the induction of CIP1 by TGF beta 1 in ovarian cancer cell lines that have been previously characterized for their proliferative response to TGF beta 1. OVCA420, a cell line that is dramatically growth inhibited by TGF beta 1, significantly induced CIP1 expression in response to TGF beta 1. CIP1 induction was accompanied by a decrease in cdk2 kinase activity and cdk2 protein levels. In three other cell lines that respond weakly to TGF beta 1, CIP1 expression was not induced. To determine if TGF beta 1 induction occurs via p53, regulation of p53 RNA and protein was examined. No differences in p53 transcription, steady-state protein level, de novo synthesis, phosphorylation, or subcellular accumulation were noted. Furthermore, TGF beta 1 could not induce transcription from a consensus p53 DNA binding site in the TGF beta 1-response cell line.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1994

Management of acute and chronic lateral ligament injuries of the ankle.

Acute and chronic lateral ligament injuries of the ankle represent a common but persistent problem to orthopedic specialists. A comprehensive physical examination and classification system were proposed as an approach to this problem. Guidelines for both conservative and surgical management for acute and chronic injuries are described. A comparison of the most common lateral ligament repairs is provided, with emphasis on the benefits of the so-called anatomic repair.

Ankle Injuries↗
PubMed1993

Response to neoadjuvant chemotherapy in children with pineoblastoma.

BACKGROUND: The outlook of children with pineoblastoma treated with radiation therapy alone is extremely poor, but neoadjuvant chemotherapy has been tried only in a few cases of this rare childhood brain tumor with poor prognosis. METHODS: Three consecutive children 3 to 7 years of age received neoadjuvant chemotherapy consisting of etoposide 100 mg/m2 days 1 to 3, cisplatin 100 mg/m2 day 1, and vincristine 1.5 mg/m2 day 1, repeated every 4 weeks. After four courses of chemotherapy, patients underwent craniospinal irradiation. The radiation doses to the primary site ranged from 5040 to 5440 cGy and craniospinal axis radiation dose was 2520 to 3060 cGy. RESULTS: After chemotherapy, mild myelosuppression occurred in all three and mild to moderate bilateral high-frequency sensorineural hearing loss occurred in two of the three patients. One patient remains in near complete resolution of the tumor at 2 years after diagnosis and another remains in CR for 5 years. One patient achieved PR for 5 months but eventually died of progressive tumor. CONCLUSIONS: This study suggests that the neoadjuvant chemotherapy as used here is effective and has acceptable toxicity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

PAC-1: a mitogen-induced nuclear protein tyrosine phosphatase.

Tyrosine phosphorylation of proteins is required for signal transduction in cells and for growth regulation. A mitogen-induced gene (PAC-1) has been cloned from human T cells and encodes a 32-kilodalton protein that contains a sequence that defines the enzymatic site of known protein phosphotyrosine phosphatases (PTPases). Other than this sequence, PAC-1 is different from several other known related PTPases exemplified by PTP-1b. PAC-1 is similar to a phosphatase induced by mitogens or heat shock in fibroblasts, a yeast gene, and a vaccinia virus-encoded serine-tyrosine phosphatase (VH1). PAC-1 was predominantly expressed in hematopoietic tissues and localized to the nucleus in transfected COS-7 cells and in mitogen-stimulated T cells.

Amino Acid Sequence↗
PubMed1993

Age does not influence taxol dose intensity in recurrent carcinoma of the ovary.

BACKGROUND: In the treatment of advanced-stage ovarian cancer, it is common practice to treat elderly patients in a less aggressive fashion than young patients. This approach is based on the notion that age is associated with poor patient tolerance to aggressive chemotherapy. Relatively little data exist to support this contention. The most exciting new chemotherapy agent to be developed in the last 10 years is taxol, a diterpeniod derivative of the Northwestern yew Taxus brevifolia. METHODS: The ability to administer dose-intensive taxol to adult patients with recurrent ovarian cancer was assessed retrospectively, and the question was asked whether the administered dose intensity of taxol was unfavorably influenced by age. Forty-eight patients with recurrent ovarian carcinoma received taxol at an initial dose of 250 mg/m2 every 3 weeks. Age in this cohort ranged from 26 to 74 years, with a median of 55. Twenty-nine percent (14 of 48) of the patients treated were 61 years of age or greater. Criteria for administration of taxol included a creatinine clearance of > 45 ml/minute, minimal abnormalities in liver function tests, good performance status, and the absence of substantial comorbid disease. RESULTS: Elderly patients in this cohort (age > 60 years) did not differ from younger patients with respect to administered dose intensity, number of cycles of therapy administered, or the occurrence of serious or mild toxicities.

Adult↗