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Biomedical subjects

A Radcliffe

Publications and source records attributed to A Radcliffe.

14 recordsLinked to original sources
PubMed2006

Can the results of anorectal (abdominoperineal) resection be improved: are circumferential resection margins too often positive?

Carefully executed surgery for rectal cancer has reduced the incidence of local recurrence after restorative resection. Three recent large prospective series have confirmed the perception of a higher positive circumferential resection margin (CRM) rate after abdominoperineal resection. Tumour spread is different for low tumours and the surgical technique of abdominoperineal resection, perhaps better known as anorectal excision, may vary between surgeons. There is a need to redefine the place of anorectal excision and the contribution that can be made by pre-operative chemoradiation and/or extended surgery to reduce local recurrence and increase survival. Defined surgery, validated by histopathological assessment, as applied to TME surgery, would determine whether the perceived higher rates are due to the differences in routes of tumour spread or to surgically related variables. Unnecessary R1 or R2 resections and operative perforation can be minimized by an understanding of the surgical anatomy, the pattern of spread and difference in operative technique between anorectal excision and a low restorative operation. Surgical technique to maximize R0 resection should be based on a detailed understanding of the pelvic fascia and the levator ani and the use of pre-operative imaging to define lines of excision. With the adoption of even lower restorative resection (intersphincteric) there is a need to reassess the method of anorectal excision. This may be achieved by histopathological assessment of CRM positivity and MDT audit to improve results. Clinical trials are essential.

Abdomen↗
PubMed1996

The Southern California Kaiser-Permanente Chemical Dependency Recovery Program evaluation: results of a treatment outcome study in an HMO setting.

This report presents the methodology and outcomes of an evaluation of the Chemical Dependency Recovery Program (CDRP) of Southern California Kaiser-Permanente, a large group model HMO. CDRP treatment includes specialized detoxification inpatient facilities, day treatment and outpatient services. Substance use outcomes in a population of 1,986 patients consecutively entering treatment were obtained via telephone at six and twelve months post intake. For patients who consumed only alcohol at baseline (N = 621), significantly higher six month point prevalence abstinence rates were found among those who remained in treatment for a minimum of three months (89%), compared to those patients who failed to return for treatment after their intake (31%). For polydrug users (N = 1365), as contrasted with patients who utilized services only on their intake date, significantly higher six month point prevalence rates were restricted to those who remained in treatment for a minimum of six months (74% versus 21%). The evaluation documented the need for CDRP services, validated program effectiveness and highlighted areas for systematic improvement.

Adult↗
PubMed1994

New dimensions in behavioral health/primary care integration.

The case is made for the integration of primary care and behavioral health services in the HMO. Key features of a successfully integrated behavioral health service are offered, along with brief reports of integration efforts at a number of HMOs across the United States. The author believes that better value and cost efficiencies result from integration.

Continuity of Patient Care↗
PubMed1991

Cross-resistance of an amsacrine-resistant human leukemia line to topoisomerase II reactive DNA intercalating agents. Evidence for two topoisomerase II directed drug actions.

HL-60/AMSA is a human leukemia cell line that is 50-100-fold more resistant than its drug-sensitive HL-60 parent line to the cytotoxic actions of the DNA intercalator amsacrine (m-AMSA). HL-60/AMSA topoisomerase II is also resistant to the inhibitory actions of m-AMSA. HL-60/AMSA cells and topoisomerase II are cross-resistant to anthracycline and ellipticine intercalators but relatively sensitive to the nonintercalating topoisomerase II reactive epipodophyllotoxin etoposide. We now demonstrate that HL-60/AMSA and its topoisomerase II are cross-resistant to the DNA intercalators mitoxantrone and amonafide, thus strongly indicating that HL-60/AMSA and its topoisomerase II are resistant to topoisomerase II reactive intercalators but not to nonintercalators. At high concentrations, mitoxantrone and amonafide were also found to inhibit their own, m-AMSA's, and etoposide's abilities to stabilize topoisomerase II-DNA complexes. This appears to be due to the ability of these concentrations of mitoxantrone and amonafide to inhibit topoisomerase II mediated DNA strand passage at a point in the topoisomerization cycle prior to the acquisition of the enzyme-DNA configuration that yields DNA cleavage and topoisomerase II-DNA cross-links. In addition, amonafide can inhibit the cytotoxic actions of m-AMSA and etoposide. Taken together, these results suggest that the cytotoxicity of m-AMSA and etoposide is initiated primarily by the stabilization of the topoisomerase II-DNA complex. Other topoisomerase II reactive drugs may inhibit the enzyme at other steps in the topoisomerization cycle, particularly at elevated concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Amsacrine↗
PubMed1991

Epstein-Barr virus shedding in breast milk.

One hundred healthy women already donating to the Children's Hospital Breast Milk bank consented to provide a sample of breast milk for this study. Using a DNA-DNA hybridization dot-blot assay Epstein-Barr virus (EBV) genome (Bam HIW region) was detected in cells shed into breast milk of 46 out of 100 women studied and in 60 out of 132 (46%) of samples donated overall. The prevalence of EBV shedding increased postnatally to a peak of 74% (26/35 positive samples) between 3 and 12 weeks postdelivery. Women delivering prematurely had an initially lower prevalence of shedding with only six out of 30 (20%) positive samples in the first week after delivery, compared to 16 out of 35 (46%) for women delivering at term. Of the 18 women donating more than one sample, 13 showed consistently positive (n = 8) or negative (n = 5) results, and the remaining five had intermittent shedding detected. Only seven out of 42 (17%) breast milk samples studied were EBV-IgG antibody positive, and none showed IgM or IgA-EBV antibodies. Further studies and prospective followup of infants are needed to confirm that breast milk is a significant source for early EBV infection of infants, as indicated by serologic studies.

Antibodies, Viral↗
PubMed1989

Characterization of an amsacrine-resistant line of human leukemia cells. Evidence for a drug-resistant form of topoisomerase II.

HL-60/AMSA is a human leukemia cell line that is 100 times more resistant to the cytotoxic actions of the antineoplastic, topoisomerase II-reactive DNA intercalating acridine derivative amsacrine (m-AMSA) than is its parent HL-60 line. HL-60/AMSA cells are minimally resistant to etoposide, a topoisomerase II-reactive drug that does not intercalate. Previously we showed that HL-60 topoisomerase II activity in cells, nuclei, or nuclear extracts was sensitive to m-AMSA and etoposide, while HL-60/AMSA topoisomerase II was resistant to m-AMSA but sensitive to etoposide. Now we show that purified topoisomerase II from the two cell lines exhibits the same drug sensitivity or resistance as that in the nuclear extracts although the magnitude of the m-AMSA resistance of HL-60/AMSA topoisomerase II in vitro is not as great as the resistance of the intact HL-60/AMSA cells. In addition HL-60/AMSA cells are cross-resistant to topoisomerase II-reactive intercalators from the anthracycline and ellipticine families and the pattern of sensitivity or resistance to the cytotoxic actions of the various topoisomerase II-reactive drugs is paralleled by topoisomerase II-reactive drug-induced DNA cleavage and protein cross-link production in cells and the production of drug-induced, topoisomerase II-mediated DNA cleavage and protein cross-linking in isolated biochemical systems. In addition to its lowered sensitivity to intercalators, HL-60/AMSA differed from HL-60 in 1) the susceptibility of its topoisomerase II to stimulation of DNA topoisomerase II complex formation by ATP, 2) the catalytic activity of its topoisomerase II in an ionic environment chosen to reproduce the environment found within the living cell, and 3) the observed restriction enzyme pattern on a Southern blot probed with a cDNA for human topoisomerase II. These data indicate that an m-AMSA-resistant form of topoisomerase II contributes to the resistance of HL-60/AMSA to m-AMSA and to other topoisomerase II-reactive DNA intercalating agents. The drug resistance is associated with additional biochemical and molecular alterations that may be important determinants of cellular sensitivity or resistance to topoisomerase II-reactive drugs.

Adenosine Triphosphate↗
PubMed1980

The effect of different calorific doses of carbohydrate on nitrogen excretion after surgery.

The protein-sparing effect of different calorific regimens [0.025 MJ (6 kcal); 0.105 MJ (25 kcal); 0.167 MJ (40 kcal) per kg body weight per 24 h] of postoperatively infused glucose has been studied in 18 patients undergoing operations of intermediate severity. Carbohydrate infusion has a progressive nitrogen-sparing effect. However, the increased negative nitrogen balance associated with surgical stress could not be prevented completely.

Adult↗
PubMed1980

The serum sodium concentration after surgical operation: precision permits predictions.

In view of previous conflicting reports, the distribution of a water overload was investigated in 6 healthy volunteers. The fall in serum sodium was predictable from prior measurement of total body water (tritium) confirming that the induced hyponatraemia was dilutional. Using a standard intravenous fluid regimen, a prospective study for 6 days on 50 patients undergoing major abdominal surgery established a confidence band for change in serum sodium concentration. This band not only enables precise prediction of whether observed sodium values in patients are "normal' for that point in their postoperative course, but also demonstrates that changes are more prolonged than was at first thought. Their dilutional nature following uncomplicated surgery is supported by linear relationships between serum osmolality and serum sodium (s-Osm = 1.86 [s-Na+] + 18:74; (P < 0.001) and between observed and calculated osmolality (Obs-Osm = 0.97 [Calc-Osm] + 15.11; P < 0.001). More detailed investigation of 14 patients by isotope dilution provided independent evidence of dilutional change. This conclusion is additionally supported by lesser changes in patients on a more restricted fluid regimen. As a practical confirmation of the utility of this approach, departures from the simple dilutional relationships were observed in 7 critically ill patients whose postoperative course was complicated. In this group osmolal "gags' of 20-50 mosmol/kg were identified. Current standard postoperative fluid regimens cause dilutional changes; these are predictable and provide a yardstick for use in management of both the healthy and the ill surgical patient.

Adult↗
PubMedDate not supplied

Ultrasonic homogenization of expressed human milk to prevent fat loss during tube feeding.

Effective use of expressed human milk in infant feeding requires proper handling, processing, storage, and administration in order to maintain its unique nutritional properties. One of the problems with expressed human milk is the separation of fat during processing, storage, and administration to the infant. Administration by continuous nasogastric infusion, either by intermittent gravity flow or by continuous mechanical pump, resulted in significant loss of fat and variation in the constitution of the milk delivered. Homogenization by ultrasonic treatment prevented changes in fat concentration during infusion and essentially eliminated loss of this nutrient during administration. The conditions necessary to achieve fat dispersion and stabilization of fat particles in human milk by ultrasonic treatment are described.

Animals↗