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Biomedical subjects

R Jones

Publications and source records attributed to R Jones.

At least 253 records · Page 14Linked to original sources
PubMed1999

Expression and function of CXC and CC chemokines in human malignant liver tumors: a role for human monokine induced by gamma-interferon in lymphocyte recruitment to hepatocellular carcinoma.

Chemotactic cytokines (chemokines) play an important role in the recruitment of lymphocytes to tissue by regulating cellular adhesion and transendothelial migration. This study examined the expression and function of CXC (human monokine induced by gamma-interferon [HuMig], interleukin-8 [IL-8], and interferon-inducible protein-10 [IP-10]) and CC (macrophage inflammatory protein-1alpha [MIP-1alpha], MIP-1beta, regulated upon activation normal T lymphocyte expressed and secreted (RANTES), and macrophage chemoattractant protein-1 [MCP-1]) chemokines and their respective receptors on lymphocytes infiltrating human liver tumors. Chemokine and chemokine receptor expression was assessed by immunohistochemistry, flow cytometry, in situ hybridization and ribonuclease (RNAse) protection assays and function by in vitro chemotaxis of tumor-derived lymphocytes to purified chemokines and to HepG2 tumor cell culture supernatants. Tumor-derived lymphocytes showed strong chemotactic responses to both CC and CXC chemokines in vitro and expressed high levels of CXCR3 (HuMig and IP-10 receptor) and CCR5 (RANTES, MIP-1alpha, and MIP-1beta receptor). Expansion of tumor-derived lymphocytes in recombinant IL-2 increased expression of CXCR3. The corresponding chemokines were detected on vascular endothelium (HuMig, IL-8, MIP-1alpha, and MIP-1beta) and sinusoidal endothelium (HuMig, MIP-1alpha, MIP-1beta) in hepatocellular carcinoma. In vitro, HepG2 cells secreted functional chemotactic factors for tumor-derived lymphocytes that could be inhibited using anti-CCR5 or anti-CXCR3 monoclonal antibodies (MoAbs). Thus, lymphocytes infiltrating human liver tumors express receptors for and respond to both CXC and CC chemokines. The relevant chemokine ligands are expressed in hepatocellular carcinoma (HCC), particularly HuMig, which was strongly expressed by tumor endothelium, suggesting that they play a role in lymphocyte recruitment to these tumors in vivo. The ability of HepG2 cells to secrete lymphocyte chemotactic factors in vitro suggests that the tumor contributes to lymphocyte recruitment in vivo.

Aged↗
PubMed1999

Families as full research partners: what's in it for us?

This article describes a children's managed mental health care program that incorporates both a family participation service model and a family-initiated evaluation model. The authors begin by tracing the evolution of the family support and the participatory research movements leading to current developments in children's mental health services research. In the King County Blended Funding Project, three service systems pool funds that are spent flexibly by child and family teams. Family advocates have led efforts to design and implement the project evaluation. During this process, many tensions have arisen between meeting the demands of both scientific rigor and multiple community stakeholders. Examples are given of the issues raised by family advocates and research scientists as together they established a theory of change, identified meaningful outcomes, selected measurement tools, and implemented the evaluation protocol. Guidelines are given for how services research partnerships can be successfully built to better address community needs. This article was selected as a distinguished research paper based on a presentation by the authors at the 1998 11th annual research conference titled "A system of Care for Children's Mental Health: Expanding the Research Base." This conference is sponsored annually by the Research and Training Center for Children's Mental Health, Department of Child and Family Studies, Louis de la Parte Florida Mental Health Institute, University of South Florida, Tampa.

Child↗
PubMed1999

Ex-vivo expansion of hematopoietic progenitor cells: preliminary results in breast cancer.

Ex-vivo expanded progenitor cells have been proposed as a source of cells to support high-dose chemotherapy and to decrease or eliminate the period of neutropenia following transplantation. To date, no clinical studies using ex vivo expanded cells, have demonstrated any decrease in the time to neutrophil or platelet recovery, although a number of clinical studies have been performed using a variety of growth factor cocktails and culture conditions. Over the past 6 years we have developed a static culture system that results in optimal expansion of myeloid progenitor cells. We have initiated a clinical study to evaluate this culture system in breast cancer patients receiving peripheral blood progenitor cells (PBPC) to support high-dose chemotherapy. CD34 selected cells were cultured for 10 days in 800 ml of defined media (Amgen Inc.) containing 100 ng/ml each of rhSCF, rhG-CSF and rhMGDF in 1L teflon bags (American Fluoroseal) at 20,000 to 50,000 cells per ml. After culture the cells were washed with 3 volumes of PBS to remove all media and growth factors and reinfused on day 0 of transplant followed by daily administration of rhG-CSF. On day +1 the patients received an unexpanded PBPC product to ensure the durability of the graft. Patients transplanted with expanded PBPC cells recovered neutrophil counts (ANC > 500/microl) as early as day 4 post transplant with a median of 6 days (range 4 to 14 days). In comparison, our historical control group of patients (N=175) had a median time to neutrophil engraftment of 9 days (range 7 to 24 days). A second cohort of patients were transplanted with expanded cells alone and a similar rapid engraftment was obtained. The first patients are now over 70 days post transplant with durable engraftment. No effect on platelet recovery has been observed in any patients to date. These data demonstrate that PBPC expanded under the conditions defined can significantly shorten the time to engraftment of neutrophils.

Breast Neoplasms↗
PubMed1999

Microvessel precursor smooth muscle cells express head-inserted smooth muscle myosin heavy chain (SM-B) isoform in hyperoxic pulmonary hypertension.

The present study analyzes smooth muscle myosin heavy chain (SMMHC) expression as lung microvascular precursor smooth muscle cells (PSMCs), cells derived from fibroblasts and intermediate cells (immature SMCs), acquire a smooth muscle phenotype in an in vivo model of pulmonary hypertension (PH). Because of the unique contractile properties of the SMMHC isoform SM-B, we analyzed its expression in the microvessels (<100 micrometers diameter) and in larger vessels (100-700 micrometers) quantitatualy by the labeled [strept]avidin-biotin technique (day 1-28), and related this to cell phenotype by transmission microscopy and protein A-gold labeling (at day 28). Airway SMCs of the normal and hypertensive lung uniformly expressed SM-B whereas vascular SMC expression was heterogeneous. Thus, in some large arteries (and veins) SMCs contained cells expressing SM-B while in others all the cells were immunonegative. Microvascular cells expressing SM-B (arteries and veins) were rare in normal lung and numerous in PH, increasing as wall muscle developed in smaller segments with time. As in large vessels, some microvessels had immunopositive cells and others only negative ones. Ultrastructural analysis confirmed that the SMCs of bronchial vessels, and the septal SMCs adjoining alveolar ducts, contained dense filament arrays decorated with SM-B. While the PSMC processes of the normal lung contained sparse filaments decorated with SM-B, these cells expressed dense filament arrays in PH. Fibroblasts migrating to align around the microvessels also expressed SM-B but in the absence of a filament network. For the first time, we demonstrate in vivo that newly developed microvascular PSMCs express the SMMHC SM-B isoform in PH.

Animals↗
PubMed1999

P53 gene protein overexpression predicts results of trimodality therapy in esophageal cancer patients.

BACKGROUND: P53 protein overexpression in esophageal cancer and its correlation with response and survival after chemoradiation was retrospectively investigated. METHODS: Pretreatment and resection specimens were stained by automatic p53 immunohistochemical staining technique. RESULTS: P53 was expressed in 84.0% of esophagoscopy (EGD) biopsies; 71.4% of patients with metastasis of thoracoscopy/laparoscopy lymph nodes (TS/LS LN) identified by hematoxylin/eosin (H/E) were p53 (+); 14.2% of patients with negative TS/LS LN by H/E were p53 (+). Eleven out of 18 patients with p53 (+) in pretreatment EGD remained p53 (+) after chemoradiation; 38.8% of these patients had a pathological complete response (pCR). The median survival of this group was 15 months. Of 4 patients with p53 (-) pretreatment EGD, all of those were still p53 (-) after chemoradiation; 75% of these patients had pCR. The median survival was 30 months. In patients with p53 (+) TS/LS LN, 23% had a pCR after chemoradiation with a median survival of 16 months. In patients with p53 (-) TS/LS LN, 50.0% had a pCR with a median survival of 31.5 months. CONCLUSIONS: P53 protein overexpression in pretreatment EGD and TS/LS LN may predict response to chemoradiation and survival in esophageal cancer patients.

Adenocarcinoma↗
PubMed1999

Outcome for adjustment disorder with depressed mood: comparison with other mood disorders.

BACKGROUND: A review of the research literature on the diagnostic category of adjustment disorder indicates that its construct validity has not been established. Nevertheless, the diagnosis is made frequently, with an estimated incidence of 5-21% in psychiatric consultation services for adults. METHODS: Retrospective data was used to evaluate the construct validity of the adjustment disorder diagnostic category. The data primarily consisted of SF-36 Health Status Survey responses by a large group of adult psychiatric outpatients before treatment and again six months after beginning treatment. Subjects were divided into five diagnostic groups, and MANOVA, MANCOVA and chi square were used to clarify relationships among diagnoses, sociodemographic data and SF-36 scores. RESULTS: Diagnostic categories were significantly different at baseline, but did not differ in terms of outcome at six-months follow-up. There was a significant gender difference at baseline and a significant difference in gender distribution across diagnostic categories. LIMITATIONS: Structured interviews were not used for initial diagnoses, nor is there an estimate of the reliability of diagnoses among the clinicians. The patient attrition rate for six-months follow-up data was about 50%. Finally, patients received individualized treatment, with some patients receiving both medication and psychotherapy. CONCLUSIONS: Female patients were significantly more likely to be diagnosed with major depression or dysthymia than with an adjustment disorder. Females were also more likely than males to score lower on the mental health related scales of the SF-36 at admission. Patients diagnosed with an adjustment disorder scored higher on all SF-36 scales than did the other diagnostic groups at baseline and again at follow-up. There was no significant difference among diagnostic groups with regard to treatment outcome, suggesting that the adjustment disorder group can benefit as much as the other groups from treatment.

Adjustment Disorders↗
PubMed1999

Patient information systems that tailor to the individual.

The potential of computers in patient education has been well described by Skinner et al. One of their recommendations was for more personalized systems. In this article we discuss how computer-based patient information systems can provide material that is tailored to the individual, giving a number of examples of systems developed in Scotland. We review some of the techniques used in developing tailored systems, and consider the evidence to date as to their efficacy.

Computer-Assisted Instruction↗
PubMed1999

Recognition of faux pas by normally developing children and children with Asperger syndrome or high-functioning autism.

Most theory of mind (ToM) tests are designed for subjects with a mental age of 4-6 years. There are very few ToM tests for subjects who are older or more able than this. We report a new test of ToM, designed for children 7-11 years old. The task involves recognizing faux pas. Study 1 tested 7-9, and 11-year-old normal children. Results showed that the ability to detect faux pas developed with age and that there was a differential developmental profile between the two sexes (female superiority). Study 2 tested children with Asperger syndrome (AS) or high-functioning autism (HFA), selected for being able to pass traditional 4- to 6-year level (first- and second-order) false belief tests. Results showed that whereas normal 9- to 11-year-old children were skilled at detecting faux pas, children with AS or HFA were impaired on this task. Study 3 reports a refinement in the test, employing control stimuli. This replicated the results from Study 2. Some patients with AS or HFA were able to recognize faux pas but still produced them. Future research should assess faux pas production.

Asperger Syndrome↗
PubMed1999

High-dose therapy with autologous hematopoietic cell support as salvage treatment for patients with breast cancer who have relapsed after previous high-dose chemotherapy.

Twenty-six patients with breast cancer who had relapsed after previously receiving high-dose chemotherapy and autologous hematopoietic cell support received a second course of high-dose cytoreductive therapy and autologous hematopoietic cell support as salvage therapy. Several different high-dose therapy regimens were employed for the second transplant, including a radiolabeled immunoconjugate. Two patients died of treatment-related complications. The remaining 24 patients relapsed a median of 126 (range 22-635) days after salvage transplant. All have since died. The median survival after salvage transplant was 362 (range 31-931) days. We conclude that second courses of high-dose therapy as salvage treatment are generally well-tolerated but their efficacy is modest. Alternative treatment strategies are needed for these patients.

Adult↗
PubMed1999

Immune modulation in autologous bone marrow transplantation: cyclosporine and gamma-interferon trial.

From March 1994 to November 1994, 16 patients with high risk hematological malignancies were entered in a phase I clinical trial, designed to confirm the toxicity of cyclosporine and gamma interferon given to induce autologous graft-versus-host disease (GVHD) after autologous bone marrow transplantation (ABMT). This trial was based on the results in a rodent model, in which cyclosporine given after ABMT induces an autoimmune syndrome (autologous GVHD) identical to allogeneic GVHD. Further, this autologous GVHD is associated with a graft-versus-tumor effect augmented by interferon that upregulates MHC class II expression on normal and tumor cells, the target of the cytolytic T cells in autologous GVHD. In this trial, cyclosporine 1 mg/kg/day was given from the day of bone marrow reinfusion until the completion of the interferon and gamma-interferon. Gamma-interferon at 0.025 mg/m2 every other day was started when the total white cell count was >200 cells/ml for 2 consecutive days and continued for a total of 10 doses after ABMT. The preparative regimens were busulfan and cyclophosphamide, or cyclophosphamide with total body irradiation. All patients received 4HC-purged marrow grafts. Median age was 45 years (range 19-68). The diagnoses included chemo-resistant non-Hodgkin's lymphoma (10), acute lymphoblastic leukemia (two), chemo-resistant Hodgkin's disease (two), acute myeloid leukemia (one), and multiple myeloma (one). Median absolute neutrophil count recovery was 25.5 days (range 19-46 days). Median platelet count recovery was 40.5 days (range 28-279 days). There were nine deaths, two were related to transplant toxicity (infection), while the other seven were due to relapse. Event-free survival with a median of 964 days (range 19-1441 days of follow-up was 44%. In conclusion, treatment with cyclosporine, and gamma-interferon after ABMT was well tolerated and did not impair engraftment. Further studies with a larger number of patients are required to document any beneficial anti-tumor effect of autologous GVHD induction after ABMT.

Adolescent↗
PubMed1999

Dose intensification and molecular responses in patients with chronic lymphocytic leukaemia: a phase II single centre study.

Chronic lymphocytic leukaemia is a condition which has a median age of 65 years but approximately 10% of patients are younger than 50. Fludarabine has been shown to produce better response rates than conventional single agent or combination chemotherapy but as yet no improved survival. We have treated a series of 10 patients presenting with de novo (six) or relapsed (four) chronic lymphocytic leukaemia (CLL) with fludarabine as cytoreduction treatment and consolidation of the response with CD34 selected peripheral blood stem cell transplantation using cyclophosphamide and total body irradiation (TBI) as conditioning therapy. We report here on the progenitor cell harvest characteristics and clinical and molecular responses to both fludarabine and high-dose consolidation. Our results indicate that at 3 months post transplant clinical remissions were induced in 10/10 patients and molecular responses in 7/8 (88%) evaluable patients. Molecular relapses occurred on long-term follow-up at 6, 9, 12 and 24 months post transplant but patients continued in clinical and haematological remission. Two patients have died from progressive disease and a third patient from aggressive high grade lymphoma. Median survival from the time of transplantation for the group overall was 22 months (range 6-45). There was no procedure-related mortality in the first 100 days.

Adult↗
PubMed1999

Low-dose lansoprazole provides greater relief of heartburn and epigastric pain than low-dose omeprazole in patients with acid-related dyspepsia.

AIM: To compare the relative efficacies of lansoprazole 15 mg o.m. and omeprazole 10 mg o.m. in relieving heartburn and epigastric pain in patients with acid-related dyspepsia. In addition, the study compared the safety profiles of the two treatments. METHODS: This double-blind, parallel group, randomised, multicentre study was conducted in 52 general practices in the UK. A total of 609 patients was recruited, 562 of whom were eligible for inclusion in the intention-to-treat analysis. All of the patients had experienced at least mild heartburn or mild epigastric pain persistently on at least 4 of the previous 7 days; patients with severe symptoms were excluded. 283 patients received lansoprazole 15 mg and 279 received omeprazole 10 mg, both for 4 weeks. The main efficacy measure was relief of symptoms, based on physician assessments. RESULTS: In the intention-to-treat population, a complete relief of overall primary symptoms of dyspepsia was achieved after 2 weeks in 53% of patients receiving lansoprazole and in 41% of patients receiving omeprazole (P = 0.007). After 4 weeks, 59% of the lansoprazole group and 51% of the omeprazole group had achieved complete symptom relief (P = 0. 078). Antacids were taken for additional relief of symptoms in fewer patients given lansoprazole compared to the omeprazole group in the third and fourth weeks (P = 0.035) and also significantly fewer antacids were taken by patients in the lansoprazole group compared with patients in the omeprazole group (P = 0.033). The proportion of patients reporting adverse events was similar in both groups. CONCLUSION: Low-dose lansoprazole is more effective than low-dose omeprazole in the treatment of patients with mild heartburn or epigastric pain in general practice.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1999

Patient-controlled analgesia using remifentanil in the parturient with thrombocytopaenia.

Patient-controlled intravenous remifentanil was used to provide analgesia in labour for three thrombocytopaenic women. The most successful regimen comprised a patient-demand bolus of 0.5 microg x kg(-1) with a lockout period of 2-3 min, allowing for a successful demand with each contraction. There was an initial period during which the patient learned to anticipate the next contraction and to deliver a bolus about 30 s beforehand; subsequently the remifentanil provided excellent analgesia, with a range of consumption of 426-1050 microg x h(-1). Apart from one episode of maternal sedation and fetal heart rate decelerations resulting from an excessive demand bolus, mothers and neonates tolerated the remifentanil without sequelae. Owing to rapid metabolism by tissue esterase, the use of remifentanil allows adequate doses of opioid to be administered to the mother to achieve good analgesia, without its accumulation in the fetus.

Adult↗
PubMed1999

Adoption of Internet technology by UK postgraduate centres: a questionnaire survey.

A survey of UK postgraduate centres during September 1997 found that almost 60% were connected to the Internet, but librarians were still the largest user group, few had more than one access point and support to users was limited. Significant progress was made during the following 18 months--by April 1999 all but one of the remaining sites had Internet access in either the postgraduate centre or in a separate library. Lack of funds and decisive policy were stated to be the most common reasons for delay in connecting. The Internet was rated highly as source of the latest research information and support for evidence-based medicine and continuing education. Expansion of the role of librarians to include assistance with sophisticated searches seemed a logical move to the majority, yet the survey suggests that a significant investment in time and money will be required to support the use of the Internet in continuing medical education in the broadest sense. It is likely that the traditional boundaries between IT departments, libraries and user groups will need to be redrawn if the technology is to be exploited effectively.

Data Collection↗
PubMed1999

Subcutaneous calcification as a late effect of orthovoltage chest wall irradiation.

Adjuvant radiotherapy to the breast or chest wall is given to some patients with breast cancer, to reduce the risk of local recurrence. It is known to be associated with various late sequelae, including subcutaneous fibrosis, telangiectasia and pulmonary fibrosis. Delivering radiotherapy to the chest wall and nodal drainage areas presents the technical problem of matching the glancing and anterior supraclavicular fields. Overlap between these fields will result in underlying tissues receiving a larger dose than intended; similarly, a gap results in an inadequate dose. We present the case history of a patient with subcutaneous calcification occurring as a late sequela of radiotherapy to the chest wall and anterior supraclavicular field. This has not been previously reported and is thought to have arisen from a high dose region in an area of overlap between fields.

Breast Neoplasms↗
PubMed1999

Technique for intraoral inverted 'L' osteotomy.

The technique of intraoral inverted 'L' osteotomy mandibular advancement is technically straightforward and has a low morbidity. It is indicated for mandibular advancement, particularly when the risk of inferior alveolar (dental) nerve damage is unacceptable.

Adolescent↗
PubMed1999

Effect of gender, treatment site and psychiatric comorbidity on quality of life outcome in substance dependence.

Patients receiving treatment for substance dependence frequently endorse high rates of psychological impairment and other measures of reduced quality of life. We conducted a baseline and six-month follow-up study of a series of one hundred and three unselected patients receiving treatment for a substance abuse or dependence problem. Women and patients requiring in-patient detoxification demonstrated the most psychological impairment at baseline, as measured by the mental component summary of the SF-36. Inpatient site of treatment was associated with continued psychological impairment six months following treatment. More aggressive psychiatric and psychological interventions may be indicated for women and for inpatient substance dependence populations.

Adult↗