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Biomedical subjects

R B Jones

Publications and source records attributed to R B Jones.

At least 217 records · Page 12Linked to original sources

New treatments for Chlamydia trachomatis.

Standard regimens of tetracycline, doxycycline, or erythromycin, if compiled with, appear to be effective against Chlamydia trachomatis infections under most circumstances. However, the organism may sometimes persist despite what would seem to be adequate therapy. How often this occurs, to what extent noncompliance is the issue, and the role antibiotic resistance plays remain to be determined. Among newer antibiotics, azithromycin appears to be effective in the treatment of uncomplicated urogenital C. trachomatis infections. Single-dose therapy with azithromycin may be especially useful in overcoming compliance problems associated with the treatment of sexually transmitted disease.

Anti-Bacterial Agents↗

Genetic and experiential manipulation of fear-related behavior in Japanese quail chicks (Coturnix coturnix japonica).

We examined effects of environmental enrichment and regular handling on fear-related responses in chicks of Japanese quail (Coturnix coturnix japonica) selected over several generations for short or long tonic immobility (STI and LTI, respectively). STI chicks froze less, vocalized and walked sooner and more in an open field, emerged sooner from a hole-in-the-wall box, and showed shorter TI reactions than did chicks of the LTI line. Similarly, environmental enrichment reduced silence and inactivity in the open field, accelerated emergence, and attenuated TI. Regular handling promoted open-field vocalization and reduced the duration of TI but exerted no other significant effects. Principal component analysis showed that the responses in the 3 tests were not independent, which implies that they measured the same underlying factor. The genetic and experiential manipulation of stimulus-specific fears and of general fearfulness is discussed.

Age Factors↗

BCNU treatment of marrow stromal monolayers reversibly alters haematopoiesis.

The marrow stromal microenvironment is essential for maintaining normal haematopoiesis. Chemotherapy drugs, such as the nitrosoureas, may impair the ability of the stroma to support haematopoiesis. To assess the effects of 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) on in vitro haematopoiesis, stromal monolayers were treated with BCNU, 5 micrograms/ml weekly for 3 weeks, then seeded 24 h after the third treatment with haematopoietic progenitors. Three weeks after seeding, total adherent and non-adherent cell numbers were similar in treated and control flasks as were adherent granulocyte/macrophage colony forming cell (GM-CFC) numbers. In contrast, non-adherent GM-CFC were significantly reduced in treated flasks, to 40-60% of controls. However, no reduction in non-adherent GM-CFC number was seen if seeding was delayed for 7 d following BCNU treatment, suggesting the effects are reversible. Conditioned media from treated and control monolayers, harvested at a time corresponding to the time of seeding, showed no difference in colony stimulating activity. In addition, extracts of bound growth factors from treated and control monolayers also showed no differences in colony stimulating activity. Thus, BCNU can alter haematopoiesis through a reversible effect on the marrow stroma and this effect does not appear to be mediated by a change in stromal growth factor production.

Bone Marrow↗

Computer literacy among medical, nursing, dental and veterinary undergraduates.

Universities need to ensure that clinical undergraduates are educated in the use of computers in medical, nursing, dental and veterinary practice. We surveyed 875 students at Glasgow University to determine their computer literacy and attitudes to the use of computers. One in five students had not used a computer during the last year and 16% thought themselves to be a complete novice with computers. Medical students were more likely to have used a computer recently compared to dental and nursing students. For one in four students, the idea of working with a computer makes them anxious. Seventy per cent of students wanted more use of computers in the curriculum and 30% applied to attend an optional computing course in the summer. Although a third of students had not used a computer at school, the proportion had increased a little in recent years. At Glasgow University, changes need to be made to the undergraduate curriculum to teach students the use of computers in clinical practice. With a few exceptions, there is no reason to believe that this does not apply to other British universities.

Attitude of Health Personnel↗

4-Hydroperoxycyclophosphamide purging of breast cancer from the mononuclear cell fraction of bone marrow in patients receiving high-dose chemotherapy and autologous marrow support: a phase I trial.

We designed an ex vivo bone marrow treatment for breast cancer patients receiving high-dose chemotherapy and autologous bone marrow support (ABMS), using 4-hydroperoxycyclophosphamide (4-HC), an active derivative of cyclophosphamide with known activity against breast cancer. This phase I bone marrow purging trial used ficoll-separated mononuclear cells (MNC) (devoid of granulocytes and RBCs), as opposed to the buffy coat. Twenty-five patients with metastatic breast cancer were studied. Patients received three cycles of the Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), fluorouracil, and methotrexate (Duke AFM) regimen, followed by marrow harvest. An MNC fraction of marrow was prepared and treated with 4-HC in concentrations of 20 micrograms/mL (four patients), 40 micrograms/mL (four patients), 60 micrograms/mL (nine patients), or 80 micrograms/mL (eight patients) and cryopreserved. Patients then received high-dose systemic cyclophosphamide, cisplatin, and carmustine, followed by infusion of the purged marrow. The study end point was marrow engraftment, defined as WBC count greater than 1,000 cells per microliter. At the first three dose levels (20, 40, and 60 micrograms/mL 4-HC), there was no significant delay in time to engraftment (19, 20, and 23 days, respectively) compared with the unpurged historical controls (17 days). At 80 micrograms/mL, engraftment was significantly delayed compared with the lower concentrations (P = .027), and further escalation of 4-HC was not attempted. A significant correlation was observed between the time of leukocyte engraftment and the 4-HC concentration (P = .017). With a methylcellulose-based tissue culture assay, we demonstrated a statistically significant correlation between the colony-forming unit-granulocyte-macrophage (CFU-GM) content in the purged marrow and the days to engraftment. Ninety-five percent of patients responded clinically to the entire program, 55% of them completely. Longer follow-up is required to assess the ultimate benefit of intensive therapy on long-term survival.

Adult↗

Out of hours work in primary care: audit of an urban co-operative deputising service.

The White Paper and discussions about the GP contract have reinforced an interest in the audit of the demand for and the quality of out-of-hours cover. We audited deputising service records for the North East Deputising Service in Glasgow over one year. Six thousand eight hundred and thirty-four calls were received from a catchment population of 37,300. A sample of 468 (7%) calls was used to estimate the appropriateness of calls. A classification, based on diagnosis, classified calls as emergency, 'reasonable' or 'unnecessary'. One hundred and eighty-three out-of-hours calls were made per 1,000 patients per year, with 40 of these being at night. Twenty-three per cent of calls were considered unnecessary, 65% reasonable and 12% genuine emergencies. People living in areas of deprivation were more likely to call and more likely to make an inappropriate call. Only 1% of calls ended with telephone advice. Five per cent had to wait more than two hours after calling. The rate of calls in this study was high compared to other studies and the use of telephone advice low. Attempts should be made to make more use of telephone advice and to educate patients to make more appropriate use of services. However, the high demand from areas of deprivation should be borne in mind when calculating GP budgets.

Adolescent↗

Immunomagnetic purging of breast cancer from bone marrow for autologous transplantation.

Intensive chemotherapy with autologous bone marrow transplantation is a promising approach for the treatment of breast cancer, provided that clonogenic tumor cells do not contaminate the patient's bone marrow. We have previously demonstrated that a combination of 4-hydroperoxycyclophosphamide (4-HC) and immunomagnetic purging (IMP) with monoclonal antibodies and microspheres could remove 4-5 logs of clonogenic breast cancer cells from a 10-fold excess of human bone marrow cells. In the present report we have evaluated an apparatus for separating tumor cells from a large volume of human marrow. This apparatus will permit preparation of large volumes of purged marrow for use in studies of intensive therapy with autologous marrow support. Bone marrow progenitor cell (CFU-GM) recovery following this IMP technique was 85% of the unpurged control, and suggests that marrow recovery following high dose systemic chemotherapy will not be adversely affected. A phase I study to evaluate marrow reconstitution following IMP is underway. Preliminary data suggest that this IMP method will not delay engraftment in breast cancer patients receiving high-dose chemotherapy and autologous bone marrow support, but further study is required.

Adenocarcinoma↗

The Duke AFM Program. Intensive induction chemotherapy for metastatic breast cancer.

Forty-five patients have completed treatment with AFM, an intensive induction chemotherapy regimen composed of Adriamycin (doxorubicin, Adria Laboratories, Columbus, Ohio), 5-fluorouracil, and methotrexate with folinic acid rescue. This regimen was designed to produce rapid and extensive tumor shrinkage prior to high-dose alkylating agent chemotherapy with autologous marrow support. The overall response rate was 91%, and 38% of patients achieved complete clinical responses after a mean of 70 days on treatment. Hematologic and mucosal toxicity were extensive, but no toxic deaths were noted. AFM is a potent remission induction regimen for metastatic breast cancer, but its considerable toxicity suggests caution in its use for routine breast cancer treatment.

Adult↗

Autologous bone marrow transplantation and factor XII, factor VII, and protein C deficiencies. Report of a new association and its possible relationship to endothelial cell injury.

Four patients who underwent treatment with high-dose chemotherapy (HDC) and autologous bone marrow transplantation (ABMT) and in whom posttreatment deficiencies of Factor XII and protein C subsequently developed are reported. Factor VII or Factor X deficiencies also developed in several of these patients. Three of these patients experienced chemotherapy-related cardiac, hepatic, or pulmonary toxicity. It is believed by many that endothelial cell injury may be the underlying lesion responsible for these various organ system toxicities seen in the setting of ABMT, although direct evidence of this is lacking. It is proposed that the factor deficiencies described in this report may be an additional consequence of endothelial cell injury or dysfunction. These coagulation factor deficiencies may therefore serve as both a marker to follow these organ system toxicities with and as a useful tool to better study and understand the mechanisms underlying these events. Additionally, deficiencies of either Factor VII or Factor X developed in several patients that were of a sufficient magnitude such that factor replacement therapy would be indicated before any invasive procedures or in the event of significant hemorrhage.

Adolescent↗

Appropriateness of hospital referral for hypertension.

OBJECTIVE: To examine the efficiency of referral to an outpatient clinic and particularly the differences between referrals from general practitioners practising in health centres and those from other general practitioners. DESIGN: Retrospective audit of referral letters and case notes by comparison with externally set standards of appropriateness of referrals over two years. SETTING: Outpatient hypertension clinic at Western Infirmary, Glasgow. PATIENTS: 306 Consecutive new referrals of patients over two years (1 May 1986 to 30 April 1988), for whom case notes were available in 298. MAIN OUTCOME MEASURES: Congruence of referrals with each of two standards of appropriateness based on published opinion on specialist referral (standard 1 was stricter than standard 2) and completeness of referral letters. RESULTS: Of the 298 referrals, those from general practitioners accounted for 205, from other hospital departments 68, and from other sources 25. Overall, 84 referrals of the 205 from general practice met the first standard and 134 met the second, more lenient standard. 58 Referral letters from outside the hospital had some item missing. Referrals from general practitioners working in health centres (a fifth of the total) were significantly more likely to meet both standards (p less than 0.01) and to send a complete referral letter (p less than 0.001) than the 145 referred by other general practitioners. CONCLUSIONS: According to the standards used, general practitioners in health centres made more appropriate referrals, and further investigation is needed to identify the underlying factors responsible.

Ambulatory Care↗

In vivo biliary excretion and in vitro cellular accumulation of thyroxine by rats or cultured rat hepatocytes treated with a novel histamine H1-receptor antagonist.

Rats treated with temelastine (SK&F 93,944), a novel histamine H1-receptor antagonist, develop thyroid lesions characterized by hypertrophy and colloid depletion. To investigate the mechanism underlying the lesion the biliary clearance and hepatocellular accumulation of radio-labelled iodothyronines was measured in rats or cultured rat hepatocytes. Treatment with temelastine increased both the biliary clearance (approximately 300% of control) and hepatocellular accumulation (approximately 200%) of thyroxine (T4) but had little or no effect on tri-iodothyronine (T3). Chromatographic analysis of bile samples from temelastine-treated rats showed that the majority (approximately 78%) of T4 was present in the unconjugated form. This contrasted with data from phenobarbitone-treated rats which showed that approximately 80% of T4 in the bile was present as the glucuronide conjugate. Studies with cultured hepatocytes showed that the hepatocellular accumulation of T4 was energy dependent. At 4 degrees C the treatment-related increases in accumulation of T4 were abolished, suggesting that temelastine is specifically affecting the high affinity, energy dependent system which preferentially transports thyroxine into hepatocytes. Because temelastine is metabolized extensively, investigations were undertaken to discover if the hepatic effects were caused by the parent compound or an oxidative metabolite. The results showed that the hepatocellular accumulation of T4 remained increased in hepatocytes co-incubated with temelastine and 1-aminobenzotriazole (a suicide inhibitor of cytochrome P450), even though no measurable P450 could be found in the cells. Also, in studies with two major "rat" metabolites of temelastine, i.e. 93,944-Met I or 93,944-Met VIII, treatments failed to reproduce the responses seen with the parent compound.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

High-dose carboplatin, cyclophosphamide, and BCNU with autologous bone marrow support: excessive hepatic toxicity.

Intensive doses of carboplatin, cyclophosphamide, and BCNU with autologous bone marrow support were given to four patients with advanced melanoma. Three developed clinically diagnosed, severe veno-occlusive liver disease, which was fatal in two cases. The dose of carboplatin (450 mg/m2) was comparable with that used in ambulatory regimens. At the doses and schedule employed, this three-drug combination produced excessive hepatic toxicity. Caution is suggested when giving carboplatin in combination with intensive doses of other chemotherapeutic agents with known hepatotoxic potential.

Adult↗

The specific psychosocial effects of orthognathic surgery.

This study was to test the validity of patients' opinions and provide a more accurate method than previously reported of assessing the specific psycho-social effects of orthognathic surgery. Questionnaires were used preoperatively and postoperatively providing a longitudinal sample, while those patients who only completed questionnaires either before or after surgery provided cross-sectional samples. Different questionnaires were used to provide data on a 'Body Satisfaction Scale', 'Fear of Negative Evaluation', 'Social Avoidance and Distress', and a 'General Health Questionnaire'. The results indicate that surgery produced an improvement in body image, particularly in the evaluation of facial attractiveness.

Adult↗

Partial characterization of Chlamydia trachomatis isolates resistant to multiple antibiotics.

In vitro susceptibility testing was done on urogenital isolates of Chlamydia trachomatis from five patients, four of whom were suspected treatment failures. At least one isolate from each patient was resistant to tetracycline at concentrations greater than or equal to micrograms/ml, although less than 1% of a population of organisms showed high-level resistance. Fully resistant populations selected by passage through 8 micrograms/ml tetracycline either died or lost their resistance on further passage in antibiotic-free medium. Relatively large inocula were required to demonstrate resistance, and morphology of inclusions was altered at high tetracycline concentrations. The observed resistance may be a new characteristic of the organism or merely newly recognized. Isolates resistant to tetracycline were resistant to doxycycline, erythromycin, sulfamethoxazole, and clindamycin but sensitive to rifampin, ciprofloxacin, and ofloxacin. Thus, resistance to tetracycline, erythromycin, and clindamycin occurs in C. trachomatis and may be a factor in some treatment failures.

Acute Disease↗

Interferon-gamma in endocervical secretions of women infected with Chlamydia trachomatis.

Although interferon-gamma has been associated with control of chlamydial infections in mice, no direct evidence links it to human chlamydial infections. Therefore, interferon-gamma was assayed by ELISA in endocervical secretions and plasma of women cultured for Chlamydia trachomatis. Women with positive endocervical chlamydial cultures had increased levels of interferon-gamma in endocervical secretions (6.7 +/- 2.8, mean +/- SE, n = 47) compared with uninfected women (1.4 +/- 0.4, n = 52) (P = .002). Interferon was also present in secretions of women with gonorrhea. Higher levels were seen in secretions from older women with positive chlamydial cultures. Interferon levels in secretions did not correlate with simultaneous plasma levels, the number of organisms recovered in tissue culture, or clinical correlates of inflammation. These data suggest that interferon-gamma is present at the site of chlamydial infection; however, further experiments are needed to determine whether interferon is specifically involved in protection or is a nonspecific indicator of inflammation.

Cervix Uteri↗

Quantitative culture of endocervical Chlamydia trachomatis.

We examined the number of Chlamydia trachomatis inclusions produced in the initial passage of cell cultures of endocervical specimens from 1,231 women with positive chlamydial cultures who attended a sexually transmitted diseases clinic. Youth, white race, oral contraceptive use, and concurrent infection by Neisseria gonorrhoeae were associated with high chlamydial inclusion counts. Youth, white race, and oral contraceptive use were independent determinants of a high chlamydial inclusion count in women without concurrent gonorrhea but not in women with gonorrhea. Results of our study suggest that the degree of chlamydial excretion from the infected cervix may be influenced by characteristics of the patient being tested and may affect the ability to detect C. trachomatis in different patient groups.

Adult↗

Omeprazole in the treatment of erosive oesophagitis refractory to high dose cimetidine and ranitidine.

Forty five patients with refractory oesophagitis, defined as persisting erosive changes or ulceration despite a minimum of three months' treatment with cimetidine 3.2 g daily or ranitidine 0.9 g daily, were treated in an open trial with omeprazole 40 mg daily for up to eight weeks. Endoscopically defined healing was observed in 73% of patients after four weeks' treatment and in 91% after eight weeks' treatment. Symptoms were completely relieved in 60% of patients, improved in 34%, unchanged in 4%, and worsened in 2%. After healing patients returned to maintenance treatment with cimetidine 1.6-3.2 g daily, depending on the severity of their illness before treatment with omeprazole. By six months and 12 months only 55% and 33% of patients respectively were still in remission. This study suggests that when erosive oesophagitis is refractory to treatment with high dose cimetidine or ranitidine, treatment with omeprazole 40 mg daily for up to eight weeks is effective in inducing healing and relieving symptoms.

Adult↗