Antibiotic prophylaxis in surgery.
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Anti-Bacterial Agents↗
Biomedical subjects
M Jones
Publications and source records attributed to M Jones.
Preclinical antitumor evaluation of bis-acetato-ammine-dichloro-cyclohexylamine platinum(IV): an orally active platinum drug.
The cytotoxicity of a novel platinum(IV) complex, bis-acetato-amminedichloro-cyclohexylamine platinum(IV) (JM216), has been evaluated in vitro against a panel of human tumor cell lines (predominantly ovarian) representative of models of intrinsic and acquired to cisplatin. In addition, the activity of JM216 administered by the p.o. route has been determined in vivo using the murine ADJ/PC6 plasmacytoma and four human ovarian carcinoma xenograft lines. In vitro, against seven human ovarian carcinoma cell lines, JM216 showed similar cytotoxicity and pattern of cytotoxicity to cisplatin (mean 50% inhibitory concentrations of 3.5 microM for cisplatin and 1.7 microM for JM216). The cytotoxicity of JM216 was more dependent on the time of drug exposure than that of cisplatin, suggesting that extended split-dosing rather than a single bolus administration might be a more appropriate schedule in patients. Using six pairs of acquired cisplatin-resistant and parent human tumor cell lines (four ovarian, one testicular, and one cervical) JM216 exhibited non-cross-resistance (resistance factor of < 1.5) in three whereas tetraplatin exhibited partial or full cross-resistance in all six pairs. Notably, in two of the acquired cisplatin-resistant lines (41McisR and HX/155cisR) where JM216 retained activity, resistance has previously shown to be due primarily to reduced platinum uptake. In vivo, following p.o. administration using the cisplatin-sensitive murine ADJ/PC6 plasmacytoma, JM216 showed antitumor selectivity far superior to that observed for either cisplatin, carboplatin, or tetraplatin. Across four human ovarian carcinoma xenografts of widely differing sensitivity to cisplatin and carboplatin, JM216 exhibited p.o. activity, broadly comparable to that observed for i.v. administered cisplatin and carboplatin and markedly superior to i.p. administered tetraplatin. These antitumor properties suggest that JM216 provides a structural lead to platinum complexes which may circumvent transport-determined acquired resistance to cisplatin and is a suitable candidate as an p.o. administrable platinum complex for phase I clinical trial.
Animals↗
Screen detected high blood pressure under 40: a general practice population followed up for 21 years.
OBJECTIVE: To assess hypertension detected under 40 in a general practice population. DESIGN: Prospective case-control study. SETTING AND SUBJECTS: Former coal mining community in south Wales. Systematic case finding for hypertension and associated risk factors applied to a mean total population of 1945 from age 20 on a five year cycle through 21 years. Mean population aged 20-39, 227 men and 213 women. Case criteria: age < 40 and mean systolic pressure > or = 160 mm Hg or diastolic pressure > or = 100 mm Hg. Age and sex matched controls randomly sampled from the same population. MAIN OUTCOME MEASURES: Mean initial pressures and pressures at follow up in 1989 or preceding death, and all cardiovascular events. RESULTS: 25 men and 16 women met criteria. Estimated five yearly inceptions were 26/1000 for men and 18/1000 for women. Male group mean initial blood pressure was 164/110 mm Hg for cases, falling to 148/89 mm Hg at follow up. Five male cases died at mean age 47.8, compared with two controls at 49.5. Female group mean initial pressure was 172/107 mm Hg for cases, falling to 145/86 mm Hg at follow up. One female case died aged 50, no controls. 10 male cases had non-fatal cardiovascular events at mean age 40.2, compared with two controls at mean age 50.5. Four female cases had non-fatal events at mean age 47.2, compared with one control aged 58. Male differences were statistically significant. CONCLUSIONS: Hypertension under 40 is dangerous, commoner in men than women, rarely secondary to classic causes, and may be controlled in general practice on a whole community basis.
Adult↗
Lymphatic endothelium isolation, characterization and long-term culture.
Using a collagenase trypsin-EDTA treatment, we have been able to successfully isolate and grow primary cultures of the lymphatic endothelium (LEC) that were subcultured, frozen for storage, subsequently thawed with good recovery and growth, and serially subcultured. The morphological features of cultured LEC were consistent with that observed for the endothelium of intact lymphatic vessels. A prominent feature of growing cultures was the appearance of large vacuoles in the perinuclear region of the cytoplasm, which became filled with fluid and cell debris engulfed from the culture medium. The basal cell surface lacked a well defined basal lamina and anchoring filaments were observed extending from the basal plasmalemmal surface into the underlying substratum. LEC in cultures were also positive for Factor VIII-related antigen. However, specific granules, characteristic of Weibel-Palade bodies were not observed in ultrathin sections of confluent cultures. F-actin was identified in LEC cultures using fluorescein phalloidin, and in confluent cultures actin filaments were located at the periphery of the cell as a continuous circumferential thin band and short filamentous bundles in the central part of the cell. By using heparin and endothelial cell growth supplement in the culture medium we have been able to grow stable cultures of lymphatic endothelial cells that could be maintained when serially subcultured for over two years. These LEC cultures provide an in vitro model for investigating the function and biochemical properties of the lymphatic endothelium.
Animals↗
Cardiovascular flow velocity measurements by 2D Doppler imaging for assessment of vascular function.
Clinical two-dimensional (2D) Doppler ultrasound flow velocity measurement is important for determination of arterial wall shear stress, blood-tissue exchange, myocardial and valvular function. Such 2D Doppler flow velocity images are usually displayed in color, superimposed on the gray-scale, cross-section structural images of the tissue. There are several limitations to this technique of flow measurement, some due to the instrumentation and some to the way the measurement is made. In this report we concentrate on the latter, identifying the main causes of errors and distortion, and outlining the methodology for minimizing them. The suggested method takes into account the spatial location and orientation of both the ultrasound transducer and the blood vessel. It allows quantification of vascular flow patterns, thus enhancing the usefulness of this important non-invasive diagnostic tool.
Arteries↗
Modes of neuronal arbor enlargement in the ear of a postembryonic fish, Astronotus ocellatus.
New hair cells are added during postembryonic life in several species of fishes and birds. The production of new hair cells appears to require enlargement of eighth nerve arbors during growth since, at least in fish, eighth nerve neurons are added more slowly than hair cells or not at all. This situation provides an intriguing opportunity to study the mechanisms of growth of the neuronal arbors. In this paper, we report the results of studies on the postembryonic growth of eighth nerve dendritic arbors in the saccular epithelium of the cichlid fish Astronotus ocellatus. Arbor sizes and shapes were compared in small and large fish using the axonal tracer cobaltous lysine. Our data suggest that postembryonic eighth nerve arbors enlarge in 2 ways. First, arbors add new terminal endings to their distal ends. Second, whole new branches appear to be added at locations up to hundreds of micrometers proximal to the terminal endings. These 2 modes of growth suggest that more than one mechanism may be operative in controlling arbor enlargement.
Animals↗
Comment on the Nottingham Prognostic Index.
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Breast Neoplasms↗
Communication styles of children of mothers with affective disorders, chronic medical illness, and normal controls: a contextual perspective.
Research has demonstrated impaired parent-child relationships in families with affective disorders. The present study examines the association of children's interactional style during a direct conflict-solving task to both the mother's interactional style and the child's diagnostic status. The sample includes 63 children, ages 8 to 16, of mothers with affective disorders, chronic medical illness, and normal controls. Children's dominant coping style profile (CS) (autonomous, neutral, or critical) was related to their mother's affective style (AS) (benign or negative). Affective disorder in the child at 6-month followup was associated with a critical CS profile at intake, while the child's nonaffective symptomatology was unrelated to CS. Findings indicate that children's affective disturbance is linked to interpersonal deficits in affectively charged situations. Results suggest that the child's CS is more strongly predicted by maternal AS than by either the child's or the mother's diagnostic status.
Adaptation, Psychological↗
Accuracy of flow convergence estimates of mitral regurgitant flow rates obtained by use of multiple color flow Doppler M-mode aliasing boundaries: an experimental animal study.
The proximal flow convergence method of multiplying color Doppler aliasing velocity by flow convergence surface area has yielded a new means of quantifying flow rate by noninvasively derived measurements. Unlike previous methods of visualizing the turbulent jet of mitral regurgitation on color flow Doppler mapping, flow convergence methods are less influenced by machine factors because of the systematic structure of the laminar flow convergence region. However, recent studies have demonstrated that the flow rate calculated from the first aliasing boundary of color flow Doppler imaging is dependent on orifice size, flow rate, aliasing velocity and therefore on the distance from the orifice chosen for measurement. In this study we calculated the regurgitant flow rates acquired by use of multiple proximal aliasing boundaries on color Doppler M-mode traces and assessed the effect of distances of measurement and aliasing velocities on the calculated regurgitant flow rate. Six sheep with surgically induced mitral regurgitation were studied. The distances from the mitral valve leaflet M-mode line to the first, second, and third sequential aliasing boundaries on color Doppler M-mode traces were measured and converted to the regurgitant flow rates calculated by applying the hemispheric flow equation and averaging instantaneous flow rates throughout systole. The flow rates that were calculated from the first, second, and third aliasing boundaries correlated well with the actual regurgitant flow rates (r = 0.91 to 0.96). The mean percentage error from the actual flow rates were 151% for the first aliasing boundary, 7% for the second aliasing boundary, and -43% for the third aliasing boundary; and the association between aliasing velocities and calculated flow rates indicates an inverse relationship, which suggests that in this model, there were limited velocity-distance combinations that fit with a hemispheric assumption for flow convergence geometry. The second aliasing boundary with an aliasing velocity, of 102 cm/sec, (which was achieved by use of a 4 kHz pulse repetition frequency, a 3.75 MHz transducer, and no color baseline shift), provided the closest fit to the actual regurgitant flow rates (r = 0.99; y = 0.95x + 0.07). The averaged calculated flow rates from all aliasing velocities also resulted in excellent correlation (r = 0.97; y = 0.99x + 0.5). A hemispheric flow convergence method that is based on color Doppler M-mode echocardiography is a feasible and automatable method for quantifying mitral regurgitant rate.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Mood state as a predictor of treatment outcome after in vitro fertilization/embryo transfer technology (IVF/ET).
The association between mood state and treatment outcome after In Vitro Fertilization/Embryo Transfer (IVF/ET) was assessed in a prospective sample of 330 women, of whom 113 were first time participants (inductees) and 217 were repeat cycle women (veterans). Initial evaluation of mood state indicated a significantly higher level of depression amongst veterans than inductees and a significantly greater proportion of veterans (25%) with clinically elevated depression scores compared with inductees (15%) and community norms (approx. 12%). Up to 12 months after initial assessment and after controlling for the number of treatment cycles, a significant difference was observed in the course of pregnancy over time between depressed and non-depressed women. Depressed women exhibited a lower pregnancy rate for the first treatment cycles than non-depressed women. The results and their implications are discussed.
Adult↗
Audit of nutritional advice given to bone marrow transplant patients in the United Kingdom and Eire.
OBJECTIVE: To determine the dietary advice, catering practices, anthropometry and nutritional support given to bone marrow transplant (BMT) patients in the United Kingdom and Eire and to compare current advice with published literature recommendations. DESIGN: Questionnaire survey completed by consultants and dietitians. SETTING: 43 hospitals undertaking autografts and/or allografts. PARTICIPANTS: Consultant Haematologists and Senior Dietitians. RESULTS: A 75% response rate was achieved. There is a wide variation in both dietary advice and nutritional support given to BMT patients. CONCLUSION: The wide variations in clinical practice reflect the lack of research in this area. The current problems of giving advice are discussed and some specific suggestions are made. Advice needs to be consistent and within the limitations of existing research.
Journal Article↗
Acquisition of platinum drug resistance and platinum cross resistance patterns in a panel of human ovarian carcinoma xenografts.
In vivo models of acquired resistance to the platinum-based agents cisplatin (CDDP), carboplatin (CBDCA), iproplatin (CHIP) and tetraplatin have been established using a panel of six parent human ovarian carcinoma lines, two (HX/110 and PXN/87) being derived from previously untreated patients. Resistance has been generated to CDDP (three lines), CBDCA (one line), CHIP (three lines) and tetraplatin (one line) either by treatment in vivo or (for one line to CDDP) through exposure in vitro and subsequent transfer to mice. With the four tumours where resistance was generated using CDDP or CBDCA, a complete cross-resistance to the remaining platinum agents studied was observed. In contrast, in one of three lines with derived resistance to the platinum (IV) agent, CHIP, (PXN/951) a retention in sensitivity was observed with CDDP and CBDCA. Only one of the six parent tumour lines (PXN/100) was markedly sensitive to tetraplatin. Where resistance was generated to tetraplatin (PXN/100T) there was some retention of activity by CDDP. For the CDDP-resistant line established in vitro, there was a close agreement between the cross-resistance profile obtained in vitro vs that obtained in vivo. This tumour panel may be useful in the elucidation of cellular and molecular resistance mechanisms to platinum drugs operative in vivo. Moreover, as they appear to mimic the clinical observations of shared cross-resistance between CDDP, CBDCA and CHIP, they may represent valuable preclinical evaluation models for the discovery of drugs capable of conferring responses in CDDP-refractory ovarian cancer.
Animals↗
Preclinical, phase I and pharmacokinetic studies with the dimethyl phenyltriazene CB10-277.
Decarbazine is an imidazole dimethyltriazene with reproducible activity in patients with metastatic melanoma. CB10-277 is a phenyl dimethyltriazene which, like dacarbazine, requires metabolic activation to its corresponding monomethyl species for antitumour activity. In preclinical models (human melanoma xenografts and transplantable rodent tumours) CB10-277 showed a similar spectrum and level of activity when compared to dacarbazine. Pharmacokinetic studies were performed with CB10-277 in mice treated i.v. at the LD10 (750 mg m-2) and plasma analysed by HPLC. The parent drug area under the plasma concentration vs time curve (AUC) was 142 mM x minutes. Drug metabolism occurred as evidenced by the HPLC identification of the monomethyl species (AUC = 8 mM x minutes) as well as other metabolites. A Phase I trial using a short infusion with doses repeated every 21 days has been performed. Thirty-six patients received 80 courses over a dose range of 80-6,000 mg m-2. The dose limiting toxicity was nausea and vomiting which occurred in 80% of the evaluable courses > or = 900 mg m-2. The only other common side effect was a flushing or warm sensation, which occurred in over 75% of courses at > or = 1,350 mg m-2. There were no hemodynamic consequences. Responses occurred in patients with melanoma (one complete, two partial, one mixed/11), sarcoma (one mixed/6) and carcinoid (one partial/l). Pharmacokinetics were performed in 46 courses. The CB10-277 AUC increased linearly with dose (r = 0.9203, P < 0.001) up to 700 mM x minutes at 6,000 mg m-2). Evidence of CB10-277 metabolism was observed, as in mice, by detection of the monomethyl species and other metabolites. However, the plasma levels of the monomethyl species in patients (1.8 and 3.7 mM x minutes at 6,000 mg m-2) were less than those predicted from studies in mice. Despite this, antitumour activity in dacarbazine sensitive histologies was observed and additional studies with CB10-277 are recommended.
Adult↗
Raised adenine nucleotide concentrations in erythrocytes of patients with cystic fibrosis.
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Adenine Nucleotides↗
Application of breath pentane analysis to monitor age-related change in free radical activity.
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Adolescent↗
Evaluation of rooms with negative pressure ventilation used for respiratory isolation in seven midwestern hospitals.
OBJECTIVE: To determine the number and efficacy of respiratory isolation facilities in St. Louis hospitals and to assess the mechanisms in place for evaluating function of hospital ventilation systems. DESIGN: A prospective multi-hospital surveillance study using direct observation and a standardized questionnaire. SETTING: Seven hospitals (including university-affiliated large teaching, private community, private teaching, and private nonteaching adult hospitals, and one pediatric teaching hospital) in St. Louis, Missouri. MEASUREMENTS: Actual direction of airflow in rooms designated for respiratory isolation was measured using smokesticks. Hospital demographic information, respiratory isolation policies, and frequency of ventilation tests were provided by infection control personnel. RESULTS: One hundred twenty-one (3.4%) of 3,574 hospital rooms were designed to have negative pressure ventilation suitable for respiratory isolation. The percentage of isolation rooms in each institution ranged from 0.4% (92 of 486) to 93% (39 of 42). Only three (43%) of seven hospitals had intensive care respiratory isolation rooms, and none had isolation rooms in the emergency department. No hospital had tested routinely the efficacy of the negative pressure ventilation, and two (28%) of seven had tested airflow for the first time in the past year. We tested 115 (95%) of 121 isolation rooms. With the doors closed, 52 (45%) of 115 designated negative pressure rooms actually had positive airflow to the corridor. The number of negative pressure rooms and the presence or absence of anterooms did not predict correct direction of airflow. There was a significant difference among hospitals in the percentage of designated isolation rooms that had truly negative pressure (P < 0.0001). Hospital age, size, and type correlated with correct direction of airflow (P < 0.0001). CONCLUSION: In the hospitals studied, only a small number of rooms were designated for respiratory isolation, and the performance of these was not tested routinely. High-risk areas including intensive care units and emergency rooms were not equipped to provide respiratory isolation. The direction of airflow in respiratory isolation rooms was not always correct and should be evaluated frequently.
Cross Infection↗
A prospective randomized trial comparing manual and automated endoscope disinfection methods.
OBJECTIVE: To compare the efficacy of endoscope disinfection using automated and manual systems. DESIGN: Prospective randomized trial. SETTING: A 1,000-bed tertiary care referral center. METHODS: All endoscopes underwent a three-stage decontamination process including brushing and cleaning with water and detergent, manual or automated disinfection with 2% glutaraldehyde, and 70% alcohol rinse with forced air drying. Cultures were obtained from endoscopes from both groups before and after alcohol rinse and then after overnight storage. RESULTS: Cultures from 8/30 (27%) automated and 11/30 (37%) manually disinfected (P = 0.58) endoscopes grew gram-negative bacteria and/or nontuberculous mycobacteria before the alcohol rinse. After alcohol rinse, 3 (10%) of 30 automated and 8 (27%) of 30 manually disinfected endoscopes remained contaminated (P = 0.28). Manually disinfected endoscopes were contaminated more frequently with coliform bacteria, whereas endoscopes undergoing automated disinfection were more frequently contaminated with nontuberculous mycobacteria, but the differences were not statistically significant. After alcohol rinse and forced air drying, there was no difference in contamination rates between freshly disinfected endoscopes and those stored overnight (7/30 (23%) versus 4/30 (13%), P = 0.50). Colonoscopes and duodenoscopes were contaminated more often than gastroscopes (P = 0.00001). CONCLUSION: The persistent endoscope contamination after manual and automated disinfection indicates the importance of developing more reliable and effective disinfection methods.
Automation↗
The impact of interleukin-2 on survival in renal cancer: a multivariate analysis.
The purpose of this analysis was to compare the survival of patients with advanced renal carcinoma treated with intravenous recombinant interleukin-2 to the survival of matched patients taken from the large and well characterised database of the Eastern Cooperative Oncology Group (ECOG). Recombinant interleukin-2 (rIL-2) given by continuous intravenous infusion was used to treat 387 patients with advanced adenocarcinoma of the kidney in five multi-centre studies and 327 of these patients fulfilled the study eligibility criteria and were evaluable for response, toxicity and survival. The survival of patients treated with rIL-2 was compared in a multi-variate survival analysis taking account of all identified prognostic factors to 390 control patients receiving chemotherapy derived from the database. Thirteen patients treated with rIL-2 achieved a complete remission of their disease and 32 a partial remission giving an overall response rate of 14%. Remissions were durable with a median duration of 357 days for partial remissions and a median duration in excess of 926 days for complete remissions. Most patients experienced fever or mild to moderate hypotension and other toxicities are described. However, only 11 patients required admission to intensive care and in only five cases was this judged to be due to treatment toxicity. There were three deaths judged to be probably due to treatment toxicity. rIL-2 treatment was associated with significantly prolonged survival compared to the ECOG control patients. Patients with good prognostic features appeared to have a greater survival benefit from rIL-2 than those with poor prognostic features. This analysis provides the first evidence that rIL-2 prolongs survival in patients with advanced renal cancer but cannot provide proof which should be sought in randomised prospective trials drawing on the hypotheses generated herein.
Adult↗