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Biomedical subjects

E Cooke

Publications and source records attributed to E Cooke.

At least 19 recordsLinked to original sources

Loss of flexor pollicis longus function after plating of the radius. Report of six cases.

Six cases of loss of flexor pollicis longus function after plating of a radius fracture are presented. The exact aetiology of the postoperative deficit is uncertain, but is probably a traction neuropraxia of the anterior interosseous nerve branches to the flexor pollicis longus. All six patients had full recovery within 5 months. An initial conservative approach is recommended if this complication is encountered.

Adolescent

Adjuvant postoperative fluorouracil-modulated chemotherapy combined with pelvic radiation therapy for rectal cancer: initial results of intergroup 0114.

PURPOSE: The combination of radiation therapy with fluorouracil (5-FU)-based chemotherapy is generally accepted as appropriate postoperative therapy for patients with adenocarcinomas of the rectum that extend through the bowel wall or with lymph nodes positive for tumor. We attempted to determine whether the efficacy of this postoperative therapy could be improved by the addition of leucovorin and/or levamisole. METHODS: A total of 1,696 patients were randomized and eligible for treatment with one of four treatment schemes. All patients received two cycles of bolus 5-FU-based systemic chemotherapy followed by pelvic radiation therapy with chemotherapy and two more cycles of the same systemic chemotherapy. Chemotherapy was either 5-FU alone, 5-FU with leucovorin, 5-FU with levamisole, or 5-FU with leucovorin and levamisole. RESULTS: With a median follow-up duration of 48 months, there is no statistically significant advantage to any of the treatment regimens compared with bolus 5-FU alone. There is evidence of increased gastrointestinal toxicity with the three-drug combination compared with bolus 5-FU alone. Statistical analysis suggests it is very unlikely that either levamisole-containing combination will be shown to be of value with further follow-up evaluation. CONCLUSION: There is no evidence at present for a beneficial effect of levamisole in the adjuvant treatment of rectal cancer. Definitive evaluation of the effect of the addition of leucovorin to 5-FU and pelvic radiation will require further follow-up evaluation.

Adenocarcinoma

Large-volume leukapheresis in pediatric patients: processing more blood diminishes the apparent magnitude of intra-apheresis recruitment.

BACKGROUND: Recruitment of progenitors during a large-volume collection, as defined by increasing relative and absolute numbers of progenitors (colony-forming units-granulocyte-macrophage [CFU-GM] of CD34+ cells), has been reported previously. STUDY DESIGN AND METHODS: To ascertain whether intra-apheresis recruitment occurs in pediatric patients who have undergone mobilization with chemotherapy and granulocyte-colony-stimulating factor (G-CSF), each hour's portion of a 4-hour leukapheresis was collected into separate bags, and assessed by complete blood count, CFU-GM, and CD34+ cell assays. Seven pediatric patients (median age, 7; range, 2-19) were studied in connection with 2 to 4 collections each, for a total of 21 collections (with hourly samples). The collections lasted for 4 hours, at an inlet rate of 1 to 3 mL per kg per minute, for daily processing totals of 5 to 12 blood volumes. (One blood volume [mL] is estimated by the patient's weight in kg x 70 mL/kg.) Smaller (younger) patients had inlet rates exceeding 2 mL per kg per minute, and larger (older) patients had rates of 1 to 1.5 mL per kg per minute. CFU-GM and CD34+ cell counts obtained each hour of the collection and divided by the first hour's value were compared by nonparametric repeated-measures ANOVA. RESULTS: Second-, third- and fourth-hour CD34+ progenitor cell counts were arithmetically higher than first-hour counts, but the trend did not reach significance (p = 0.1561). Second-hour counts were higher than first-hour counts in the overall analysis (mean +/- standard error [SE], 1.00 and 1.39 +/- 0.1, respectively; p = 0.0525) and in children older than 5 years (1.00 vs. 1.70 +/- 0.30, respectively; p = 0.0259), but not in children younger than 5 years (p = 0.8125). CFU-GM counts did not differ among the 4 hours of collection (p = 0.1717) or between the first and second hour (p = 0.9587). CONCLUSION: In larger (older) patients, from whom fewer blood volumes were collected, there is a trend toward intra-apheresis recruitment, although less than reported previously. In the smaller (younger) patients, from whom more blood volumes were collected, no trend was observed. Lack of (or submaximal) prior mobilization in previously reported studies may have facilitated intracollection recruitment. Alternatively, the larger number of blood volumes collected from the smaller (younger) patients may have masked intra-apheresis recruitment. The study documents the feasibility of large-volume, 4-hour leukapheresis in pediatric patients.

Adolescent

Women's knowledge of emergency contraception.

BACKGROUND: More widespread use of emergency contraception could help to reduce the number of unwanted pregnancies. AIM: The objective of this study was to assess women's knowledge of emergency contraception. METHOD: A questionnaire was distributed to 1290 women aged between 16 and 50 years attending 14 general practice surgeries in London over a two-week period in 1990. RESULTS: The response rate was 70%. Over three quarters of the women had heard of emergency contraception; these were mainly women who used contraception, who had higher educational qualifications or who were not Muslim. Women who were the most likely to need and to use emergency contraception--those using barrier methods--had no more accurate knowledge than women using any other method of contraception. Only 53% of barrier method users knew emergency contraception could be used as a backup when other methods failed. Only one fifth of women had heard about this method from their general practitioner or any other health professional, while half had obtained their information from the media. CONCLUSION: These results suggest that including information on emergency contraception in consultations with users of barrier methods of contraception is a small step which general practitioners and practice nurses could take to increase the use of emergency contraception.

Adolescent

Meconium testing for cocaine metabolite: prevalence, perceptions, and pitfalls.

OBJECTIVES: We determined the prevalence of prenatal cocaine use in a racially mixed sample of urban and suburban mothers and correlated its use with maternal demographics and newborn measurements. STUDY DESIGN: Meconium from 621 consecutive newborns delivered at two university-affiliated urban hospitals were assayed for benzoylecgonine. Maternal and infant characteristics were linked anonymously with the results. Statistical analysis included t test, Fisher's exact test, Duncan's multiple range analysis, and analysis of covariance, with a value of p < 0.05 considered significant. RESULTS: We found that 3.4% of meconium samples had benzoylecgonine levels exceeding 0.1 micrograms/ml. Its presence was statistically correlated with maternal and neonatal characteristics. A nurse's opinion of cocaine use was correct 22% of the time. CONCLUSIONS: Prenatal cocaine use was statistically associated with multiparity, multigravidity, late-onset and clinic-based prenatal care, public assistance, nonwhite race, and low academic achievement. A nurse's opinion was a poor predictor of maternal cocaine use. Cocaine-exposed infants were significantly smaller, and this correlated best with nonwhite background.

Birth Weight

Potent and comparable vasodilator actions of A- and B-calcitonin-gene-related peptides on the superficial subcutaneous vasculature of man.

1. Vasoactivity of human A- and B-calcitonin-gene-related peptides was studied in normal subjects, using reflectance plethysmography to measure relative changes in blood flow produced by superficial subcutaneous injections of the peptides. 2. Injection of 10(-11) mol of either peptide caused an immediate 200% increase in local blood flow and prolonged hyperaemia lasting up to 3 h. The hyperaemic response to 10(-13) mol of each peptide was significantly (P less than 0.01) smaller and shorter in duration than that elicited by 10(-11) mol of the same peptide, and 10(-15) mol of both peptides produced no hyperaemia other than that attributable to needle insertion alone. 3. At all three dosages examined, there were no significant differences between A- and B-calcitonin-gene-related peptides in magnitude or time course of the hyperaemic response. 4. Human A- and B-calcitonin-gene-related peptides are therefore potent vasodilators in man, causing comparable dose-related vasodilatation in the superficial tissues.

Adolescent

Diacylglycerol kinase inhibitor, R59022, potentiates neutrophil oxidase activation by Ca2+-dependent stimuli. Evidence for two separate but convergent pathways.

An inhibitor of diacylglycerol kinase, R59022, enhanced activation of the neutrophil oxidase stimulated by the Ca2+-ionophore, A23187 (1 microM), and by N-formyl-methionyl leucyl-phenylalanine (1 microM). The enhancement was reversed by two inhibitors of c-kinase, retinal (10 microM), and gossypol (20 microM). Activation by phorbol-myristyl-acetate and unopsonised latex beads were not enhanced. It was concluded that the chemotactic peptide generated diacylglycerol, but that maximum activation of c-kinase by this route was not achievable. The role of diacylglycerol in activation by beads remained unclear.

Animals

Inhibition of protein kinase C mediated signal transduction by tamoxifen. Importance for antitumour activity.

Recent studies have demonstrated tamoxifen inhibition of the enzyme protein kinase C (PKC) in vitro. The aim of this study was to investigate the effects of tamoxifen on PKC function in intact human cells. As PKC activates the neutrophil oxidase mechanism the neutrophil was chosen as an experimental model to assess PKC-tamoxifen interaction in these experiments. Neutrophils from healthy volunteers were separated by centrifugation through Ficoll Hypaque. Two separate parameters of oxidase activation; oxygen consumption and reactive oxygen metabolite production were monitored by a Clark electrode chamber and luminol dependent chemiluminescence respectively. Neutrophil chemiluminescence was markedly stimulated by 4 Phorbol-12 myristate-13 acetate (PMA). This stimulation was inhibited by tamoxifen; IC50 = 6.1 +/- 1.6 microM (means +/- S.E.M.) N = 6. Neutrophil oxygen consumption was similarly stimulated by PMA and inhibited by tamoxifen. The tamoxifen inhibition was not due to cell toxicity as assessment of cell integrity by the exclusion of trypan blue and measurement of intracellular concentrations of ATP showed no significant differences before and after treatment. Tamoxifen also inhibited neutrophil chemiluminescence which was stimulated by oleoyl acetyl glycerol and mezerein excluding interaction with PMA as an explanation of its inhibitory effect. These results are consistent with tamoxifen inhibition of PKC function in intact human cells. This may be central to its antitumour action.

Diglycerides

The role of C-kinase in the physiological activation of the neutrophil oxidase. Evidence from using pharmacological manipulation of C-kinase activity in intact cells.

The role of C-kinase in the triggering of the neutrophil oxidase by two stimuli (latex beads and the chemotactic peptide fMet-Leu-Phe), representative of endocytotic and exocytotic routes of activation, were investigated by using experimental agents that activate, or inhibit C-kinase, in intact cells. The activation by the phagocytotic stimulus latex beads was mimicked by C-kinase activators giving the same characteristic lag (20-30s), followed by a constant oxygen consumption rate with the same maximum rate and affinity for oxygen (Km approx. 13 microM), competed with activation by PMA (4 beta-phorbol 12-myristate 13-acetate) in a simple common-target manner, and was inhibited by retinal, an inhibitor shown to inhibit activation by PMA. In contrast, activation by chemotactic peptide was not mimicked by C-kinase activation alone, chemotactic peptide inducing biphasic oxygen consumption with a Km for oxygen of the second prolonged phase of 3.9 microM, did not compete with activation by PMA, and was not inhibited by retinal. However, PMA and retinal produced slight enhancements of activation by chemotactic peptide and production of monophasic oxygen consumption. It was concluded that C-kinase activation plays a simple central transducing role in activation of the oxidase by latex beads, but that its role in activation by chemotactic peptide is a part of a more complex set of interactions that involve other Ca2+-activated and non-Ca2+-activated processes.

Animals

Subcutaneous aprotinin causes local hyperaemia. A possible mechanism by which aprotinin improves control in some diabetic patients.

Local changes in blood flow at the subcutaneous injection site of the proteinase inhibitor aprotinin and its diluent were measured by photoelectric plethysmography. Aprotinin, but not its diluent, caused local hyperaemia in five normal subjects and in five stable and five brittle insulin-dependent diabetic patients, local blood flow increasing by 80%-180%. The duration of the hyperaemic response was shorter in the brittle diabetic patients than in the other two groups, but there was wide individual variation. Aprotinin is known to enhance subcutaneous insulin absorption in normal subjects and in some brittle diabetic patients. The basis for this might be through increasing blood flow near the injection site rather than by inhibition of insulin breakdown.

Adult

Changes in blood flow close to subcutaneous insulin injection sites in stable and brittle diabetics.

Photoelectric plethysmography (PPG) was used to investigate blood flow changes close to superficial subcutaneous injection sites. As a validation procedure, the PPG response to subcutaneous injection of a known hyperemic agent, prostaglandin E1 (10(-5) M), was shown to correlate strongly with subcutaneous blood flow changes estimated by the established technique of 133Xe washout. Changes in blood flow over the subcutaneous injection sites of insulin (Actrapid) and insulin diluent were measured by photoelectric plethysmography in six nondiabetics and in six stable and seven brittle insulin-dependent diabetics. In all subject groups, an acute increase in local blood flow was seen within 2 min of both insulin and diluent injections, probably caused by injection trauma. At diluent injection sites, this acute hyperemia faded rapidly, blood flow returning to preinjection levels within 15-20 min, and there was no further increase in blood flow in any of the subjects. Insulin injected into the nondiabetics and stable diabetics caused a pronounced increase in local blood flow, sustained for at least 60 min after injection. In the brittle diabetics, however, there was no prolonged local hyperemia, the response being significantly less than that seen in both the nondiabetics and the stable diabetics. Insulin-related hyperemia close to injection (or infusion) sites may be important in subcutaneous insulin absorption. Its near-absence in brittle diabetics may contribute to the impaired response to subcutaneous insulin characteristic of these patients.

Adult

Electrodermal activity in the affective disorders and schizophrenia.

Electrodermal activity was measured bilaterally at rest and during stimulation in 22 schizophrenic, 11 depressed and 12 anxiety state patients, and in 32 normal volunteers. No group showed a distinctive pattern of lateral asymmetry. The frequency of spontaneous fluctuation in electrodermal activity was greater in the anxiety state and schizophrenic groups and in those patients who reported auditory hallucination during recording. Few schizophrenic subjects failed to respond to visual stimulation but substantial minority failed to habituate. The implications of these findings are discussed.

Adolescent

Habituation of physiological responses in anxiety.

In the first study, 20 male and 20 female volunteers were studied under threat-of-shock and no-threat conditions with respect to anxiety levels, skin conductance, EEG auditory evoked response, and alpha-blocking variables. The threat-of-shock increased anxiety levels, skin conductance level, and fluctuations. The P300 component of the AER was greater in anxious individuals and habituation of the alpha-blocking response was retarded. In the second study, 12 anxious patients were compared with 12 normal subjects under threat-of-shock and 12 normal subjects under no-threat. Anxiety was associated with increased skin conductance fluctuations, larger P300 AER components, and impaired habituation of the alpha response.

Adult