Search PubMed⌕ Search

Biomedical subjects

J Jones

Publications and source records attributed to J Jones.

At least 343 records · Page 19Linked to original sources

Future directions in the adjuvant treatment of colon cancer.

Adjuvant chemotherapy has been shown to alter the natural history of patients with resected colon cancer. Two regimens (fluorouracil [5-FU] plus levamisole (Ergamisol) and 5-FU plus leucovorin) have been found most successful in prolonging disease-free and overall survival. When these two regimens were directly compared in randomized clinical trials, it appeared that a small disease-free survival and overall survival advantage had emerged in favor of 5-FU plus leucovorin. This advantage, in conjunction with an increased understanding of the mechanism of leucovorin's biochemical modulation of 5-FU, makes this regimen a logical choice for studies designed to further optimize and augment the clinical efficacy of chemotherapy for colon cancer. The introduction of oral tegafur and uracil (UFT) and the demonstration of significant antitumor activity with the combination of oral UFT and oral leucovorin, provide an excellent opportunity to optimize treatment with 5-FU plus leucovorin. The National Surgical Adjuvant Breast and Bowel Project has recently implemented a new clinical trial (Protocol C-06) comparing oral UFT plus leucovorin with 5-FU plus leucovorin in the treatment of patients with resected stage II and III colon cancer. The rationale for the design of the trial, inclusion and exclusion criteria, treatment regimens, and statistical considerations are reviewed.

Antidotes↗

Endometrioid adenocarcinoma of the ovary and long-term tamoxifen therapy: a coincidence or a cause for concern?

In recent years, the extensive usage of tamoxifen in patients with breast cancer has led us to acquire a great deal of knowledge of its effects on various organs in the gynecological system, especially the effect on the endometrium and the increased risk of endometrial cancer. Information on the possible potential carcinogenic effect of tamoxifen on the ovary, however, has been limited, mainly because of the overall low incidence of ovarian carcinoma. In addition, there is the confounding variable posed by the diverse here-ditary breast and ovarian cancer syndromes which tend to occur in a younger age group. Here, we present a case of a postmenopausal woman who was treated for six years with tamoxifen for breast cancer before being diagnosed with endometrioid carcinoma of the ovary. We believe that given the age of the patient and the duration of tamoxifen use, the occurrence of ovarian endometrioid carcinoma may be associated with long-term tamoxifen use.

Aged↗

Autoantibodies to nuclear envelope antigens in chronic fatigue syndrome.

We have identified and partially characterized the autoantibodies in sera of 60 patients with chronic fatigue syndrome. Approximately 52% of the sera were found to react with nuclear envelope antigens. The combination of nuclear rim staining observed in immunofluorescence microscopy and immunoblot analysis of highly purified nuclear envelope proteins provided initial characterization of these autoantibodies. Further characterization showed that some sera immunoprecipitated the in vitro transcription and translation product of a human cDNA clone encoding the nuclear envelope protein lamin B1. The autoantibodies were of the IgG isotype. The occurrence of autoantibodies to a conserved intracellular protein like lamin B1 provides new laboratory evidence for an autoimmune component in chronic fatigue syndrome.

Adult↗

Cardiology. Exercise: a review.

There is now little doubt that a lifestyle lacking in exercise can contribute to the development of heart disease. There have been many local and national initiatives to promote exercise and its relation to health and well-being, many linked to the targets set out in The Health of the Nation (DoH 1992).

Exercise Therapy↗

Restoration of alpha v beta 5 integrin expression in neoplastic keratinocytes results in increased capacity for terminal differentiation and suppression of anchorage-independent growth.

Loss of expression of specific integrins is a feature of poorly differentiated oral squamous cell carcinomas (SCCs) and cell lines derived from them. In order to test whether there is a direct link between loss of integrins and abnormal keratinocyte growth and differentiation, we 'repaired' an SCC line, H357, by transfection of its missing integrin subunit, alpha v. We analysed seven independent alpha v-expressing clones and compared them with four empty vector controls and with the parental cell line. alpha v was expressed on the cell surface as a functional alpha v beta 5 heterodimer. The parental cells expressed beta 5 mRNA and introduction of alpha v had no effect on beta 5 mRNA levels nor on cell surface levels of any other integrins examined. Introduction of alpha v had no consistent effect on the growth rate of cells on tissue culture plastic. However, anchorage-independent growth was strongly suppressed and the alpha v-transfectants showed an increased capacity for terminal differentiation, as assayed by expression of involucrin. These results are consistent with the known role of integrins in regulating keratinocyte terminal differentiation and suggest that integrin loss may be directly responsible for the abnormal behaviour of keratinocytes in a subset of oral SCCs.

Carcinoma, Squamous Cell↗

The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus.

OBJECTIVE: To develop and perform an initial validation of a damage index for systemic lupus erythematosus (SLE). METHODS: A list of items considered to reflect damage in SLE was generated through a nominal group process. A consensus as to which items to be included in an index was reached, together with rules for ascertainment. Each center submitted 2 assessments, 5 years apart, on 2 patients with active and 2 with inactive disease, of whom 1 had increased damage and the other had stable disease. Analysis of variance was used to test the factors physician, time, amount of damage, and activity status. RESULTS: Nineteen physicians completed the damage index on 42 case scenarios. The analysis revealed that the damage index could identify changes in damage seen in patients with both active and inactive disease. Patients who had active disease at both time points had a higher increase in damage. There was good agreement among the physicians on the assessment of damage in these patients. CONCLUSION: This damage index for SLE records damage occurring in patients with SLE regardless of its cause. The index was demonstrated to have content, face, criterion, and discriminant validity.

Health Status Indicators↗

EGF stimulates lamellipod extension in metastatic mammary adenocarcinoma cells by an actin-dependent mechanism.

Changes in lamellipod extension and chemotaxis in response to EGF were analysed for MTLn3 cells (a metastatic cell line derived from the 13762NF rat mammary adenocarcinoma). Addition of EGF produced a cessation of ruffling followed by extension of hyaline lamellipods containing increased amounts of F-actin at the growing edge. A non-metastatic cell line (MTC) derived from the same tumor did not show such responses. Lamellipod extension was maximal within 5 min, followed by retraction and resumption of ruffling. Maximal area increases due to lamellipod extension occurred at about 5 nM EGF. Chemotactic and chemokinetic responses, measured using a microchemotaxis chamber, were also greatest at 5 nM. Cytochalasin D inhibited EGF-stimulated responses including lamellipod extension, increases in F-actin in lamellipods, and chemotaxis. Nocodazole affected chemotaxis at higher concentrations but not EGF-induced lamellipod extension. We conclude that polymerization of F-actin at the leading edges of lamellipods is necessary for extension of lamellipods and chemotaxis of MTLn3 cells in response to EGF. The motility and chemotaxis responses of this metastatic cell line have strong similarities to those seen in well-characterized chemotactic cells such as Dictyostelium and neutrophils.

Actins↗

Regional distribution of lead in human milk from Egypt.

Bioaccumulation of lead during chronic exposure and its mobilization and secretion with mother's milk constitute a serious health hazard to the newly born children. Lead levels in human breast milk of 120 Egyptian women representing 20 different governorates throughout Egypt were determined using a graphite furnace Atomic Absorption spectrometer. According to the daily permissible intake (DPI) value established by the WHO of 5.0 micrograms/kg/d in mother's milk, the mean values of lead were around the permissible level in most of the Egyptian governorates. However, lead levels in mother's milk from Alexandria, Assiut and Cairo were significantly higher than the permissible value. Higher lead levels in mother's milk from these governorates may be attributed to heavy automobile traffic using leaded gasoline in addition to the use of lead water pipelines in these areas.

Adult↗

Maximal androgen blockade for patients with metastatic prostate cancer: outcome of a controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy. Casodex Combination Study Group.

OBJECTIVES: To review the outcome of therapy with maximal androgen blockade and compare the efficacy and safety of bicalutamide and flutamide, each used in combination with luteinizing hormone-releasing hormone analogue (LHRH-A) therapy, in patients with untreated metastatic (Stage D2) prostate cancer. METHODS: Randomized, double-blind (for antiandrogen therapy), multicenter study with a 2 x 2 factorial design. A total of 813 patients were allocated 1:1 to bicalutamide (50 mg once daily) or flutamide (250 mg three times daily), plus 2:1 to goserelin acetate (3.6 mg every 28 days) or leuprolide acetate (7.5 mg every 28 days). RESULTS: At the time of analysis (median follow-up, 49 weeks), bicalutamide plus LHRH-A was associated with a statistically significant improvement in time-to-treatment failure, the primary endpoint, when compared with flutamide plus LHRH-A. The results with longer follow-up (median, 95 weeks) support previous findings of an improved time-to-treatment failure with bicalutamide plus LHRH-A; however, the difference between groups was not statistically significant. A treatment failure endpoint was reached by 68% of patients in the bicalutamide plus LHRH-A group, compared with 72% of patients in the flutamide plus LHRH-A group. The hazard ratio of bicalutamide plus LHRH-A to flutamide plus LHRH-A was 0.87 (95% confidence interval [CI], 0.74-1.03; P = 0.10). The upper one-sided 95% confidence limit for survival was 1.00, meeting the definition for equivalence (< 1.25). With longer follow-up, overall mortality was 34%, with equivalent survival between groups: 32% of patients in the bicalutamide plus LHRH-A group died, compared with 35% in the flutamide plus LHRH-A group. The hazard ratio of bicalutamide plus LHRH-A to flutamide plus LHRH-A was 0.88 (95% CI, 0.69-1.11; P = 0.29). The upper one-sided 95% confidence limit for survival was 1.07, meeting the definition for equivalence (< 1.25). Diarrhea occurred in 24% of patients in the flutamide plus LHRH-A group compared with 10% of patients in the bicalutamide plus LHRH-A group (P < 0.001). CONCLUSIONS: In patients with metastatic prostate cancer, bicalutamide plus LHRH-A is effective and well tolerated. Because of its efficacy and tolerability profile, together with its convenient once-daily dosing formulation, bicalutamide represents a prime candidate for antiandrogen of first choice in combination with LHRH-A therapy in the treatment of men with metastatic prostate cancer.

Adult↗

Intramuscular prochlorperazine versus metoclopramide as single-agent therapy for the treatment of acute migraine headache.

To compare the efficacy of intramuscular prochlorperazine and metoclopramide in the short-term treatment of migraine headache in the emergency department 86 eligible adult patients with moderate to severe migraine headache were evaluated prospectively at a university-affiliated community hospital. After randomization, each subject received a 2-mL intramuscular injection of sterile saline, prochlorperazine (10 mg), or metoclopramide (10 mg). No other analgesics were administered during the 60-minute study period; patient assessment of relief was followed using visual analog scales. Reduction in median headache scores was significantly better among those treated with prochlorperazine (67%) compared to metoclopramide (34%) or placebo (16%). Similarly, symptoms of nausea and vomiting were significantly relieved in the prochlorperazine group (chi 2 = 17.1, P < .001). However, rescue analgesic therapy was necessary in the majority of patients treated with prochlorperazine (16/28) and metoclopramide (23/29) after the 60-minute study period. Although intramuscular prochlorperazine appears to provides more effective relief than metoclopramide, these results do not recommend either drug as single-agent therapy for acute migraine headache.

Acute Disease↗

Time of initiation and site of action of the mouse chromosome 11 imprinting effects.

Previous studies have shown that mice with paternal disomy for chromosome 11 are consistently larger at birth than their normal sibs, whereas mice with the maternal disomy are consistently smaller. An imprinting effect with monoallelic expression of some gene/s affecting growth was indicated. Here we show that the size differences become established prior to birth and are only maintained subsequently, indicating that the gene repression is limited to prenatal development. Fetal analysis was limited to 12.5-17.5 days post coitum. However by extrapolating the data backwards it could be calculated that both the maternal and paternal size effects might commence as early as 7 days post coitum, although possibly slightly later. It may be deduced that initiation of expression of the gene/s responsible may occur at about this time in development. The two disomy growth rates were mirror-images of each other, suggesting that expressed gene dosage is the underlying cause. Differential growth of the placentas of the two disomies was also found, and extrapolation of these data backwards suggested that the placental size differences were initiated later in development than those for the fetuses. The differential placental growth of the maternal and paternal disomies may therefore have developed independently or emerged as a consequence of the differential fetal growth. In either event it would seem that the expression of the responsible gene occurs in the fetus itself to cause the anomalies of growth. The data therefore provide information on the temporal and tissue specificity of the gene/s responsible for the chromosome 11 imprinting effects. Possible candidate genes are discussed.

Animals↗

Formulation and antitumor activity evaluation of nanocrystalline suspensions of poorly soluble anticancer drugs.

PURPOSE: Determine if wet milling technology could be used to formulate water insoluble antitumor agents as stabilized nanocrystalline drug suspensions that retain biological effectiveness following intravenous injection. METHODS: The versatility of the approach is demonstrated by evaluation of four poorly water soluble chemotherapeutic agents that exhibit diverse chemistries and mechanisms of action. The compounds selected were: piposulfan (alkylating agent), etoposide (topoisomerase II inhibitor), camptothecin (topoisomerase I inhibitor) and paclitaxel (antimitotic agent). The agents were wet milled as a 2% w/v solids suspension containing 1% w/v surfactant stabilizer using a low energy ball mill. The size, physical stability and efficacy of the nanocrystalline suspensions were evaluated. RESULTS: The data show the feasibility of formulating poorly water soluble anticancer agents as physically stable aqueous nanocrystalline suspensions. The suspensions are physically stable and efficacious following intravenous injection. CONCLUSIONS: Wet milling technology is a feasible approach for formulating poorly water soluble chemotherapeutic agents that may offer a number of advantages over a more classical approach.

Animals↗

The effects of acute administration of ethanol on jejunal protein synthesis and circulating insulin-like growth factor (IGF)-1 and IGF binding proteins in ad libitum fed and nutritionally restricted rats.

The effects of acute ethanol administration (75 mmol/kg body weight) to male Wistar rats (either ad libitum fed or nutritionally restricted) on fractional rates of protein synthesis in the jejunum was assessed together with the changes in IGF-1 and IGF binding protein concentrations. Acute administration of ethanol resulted in significant decreases in fractional rates of protein synthesis in the whole jejunum and jejunal seromuscular layers of both the ad libitum fed and nutritionally restricted animals. The synthesis rate per unit RNA (k(RNA), mg protein/day/mg RNA) in whole jejunum was reduced by 29% and 24% in the nutritionally restricted and ad libitum fed animals, respectively. Mean IGF-1 levels were lower in the nutritionally restricted group (871 +/- 36.9 microg/l) than the ad libitum animals (960 +/- 27.3 microg/l) although this did not reach significance. In contrast, administration of alcohol to both groups markedly reduced circulating IGF-1 levels (ad libitum: 518 +/- 19.8 microg/l, nutritionally restricted: 417 +/- 33.7 microg/l). Furthermore, ethanol treatment resulted in a three-fold increase in the intensity of a 30 kDa IGF binding protein (IGFBP) in the ad libitum fed animals and a fourfold increase in both 30 and 32 kDa IGFBP bands in the nutritionally restricted group as visualized by Western ligand blotting. Decreases in levels of IGF-1 allied with increased circulating small molecular weight IGFBPs may contribute to the reduction in fractional rates of protein synthesis in the gastrointestinal tract of ethanol-treated rats.

Journal Article↗

Comorbidity of juvenile obsessive-compulsive disorder with disruptive behavior disorders.

OBJECTIVE: To examine the full spectrum of psychiatric comorbidity in juvenile obsessive-compulsive disorder (OCD) in a naturalistic manner when no exclusionary criteria are used for sample selection. METHOD: Consecutive referrals to a specialized pediatric OCD clinic were evaluated by means of structured diagnostic interviews and rating scales. No exclusionary criteria were used for sample selection. Findings were compared with those of previously published reports of juvenile OCD. RESULTS: Compared with previous studies, our sample of juveniles with OCD had high rates of comorbidity not only with tic, mood, and anxiety disorders but also with disruptive behavior disorders. CONCLUSIONS: Our findings indicate that in the naturalistic setting, juvenile OCD is heavily comorbid with both internalizing and externalizing disorders. The presence of such a complex comorbid state has important clinical and research implications and stresses the relevance of limiting exclusionary criteria in studies of juvenile OCD.

Adolescent↗

Selection of monoclonal antibodies for the identification of D variants: ability to detect weak D and to split epD2, epD5 and epD6/7.

Red cells from known D variant donors were tested with 41 monoclonal anti-D reagents, 26 IgG and 15 IgM, with the view to selecting a panel to aid the identification of unusual D types. These antibodies gave reaction patterns which allowed the identification of most of the known D category cells, recognizing epD2, epD5, epD6/7, epD8 and epD9, but were unable to distinguish category III from normal D-positive cells. Reactivity with HMi, HMii, DFR, DBT and RoHar cells split epD2, epD5 and epD6/7 into two, three and eight groups, respectively. A panel comprising 15 monoclonal anti-D, 11 IgG and four IgM, was selected as representative of the antibodies tested. Reactivity of monoclonal anti-D was dependent on antibody concentration and antibody avidity. An antibody concentration of at least 12 micrograms/ml was required for optimum reactivity of the two monoclonal antibodies tested. A simple calculation of division of the titre by the antibody concentration provided a relatively simple means of establishing the reactivity performance of the antibody and correlated well with ability to detect weak D (Du) cells. A characteristic variable reduction in reaction strength with all the IgG anti-D was observed with weak D cells. The IgM antibodies, except the high avidity RUM-1, T3D2T6, D9A4 and BS226, performed poorly in detecting weak D. The majority of the IgM antibodies tested reacted with RoHarr cells, while only one IgG antibody was positive.

Antibodies, Monoclonal↗

Advanced life support: role of the rural registered nurse.

This paper provides a human face to advanced life support (ALS) and its assention within rural nursing practice. Over the past 5 years the issue of defibrillation and who performs it has been debated. This paper will add to the discussion. It examines the history surrounding the development of ALS, education within the hospital and isolated rural setting competency testing. It questions the limited role of current nursing practice and makes recommendations for stretching the boundaries of the nursing role in ALS. Emphasis is placed on the rural perspective and its consequent implications for individuals living in a rural environment.

Community Health Nursing↗