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Biomedical subjects

C Moore

Publications and source records attributed to C Moore.

At least 217 records · Page 12Linked to original sources

Priming and recognition of transformed three-dimensional objects: effects of size and reflection.

In 2 experiments exploring memory for unfamiliar 3-dimensional objects, Ss studied drawings under conditions that encouraged encoding of global object structure. Implicit memory for objects was assessed by a judgment of structural possibility; explicit memory was assessed by recognition. The principal manipulation was the relationship between the sizes or the left-right parities of the studied and tested objects. Priming was observed on the possible-impossible object decision task despite transformations of size or reflection. Recognition, by contrast, was significantly impaired by the transformations. These results suggest that a structural description system constructs representations of objects invariant over size and reflection, whereas a separable episodic system encodes these transformations as properties of an object's distinctive representation in memory.

Adult↗

Etoposide plus carboplatin admixture. Phase I study of five- or seven-day continuous infusion.

Thirty-five patients were entered in a Phase I trial of an admixture infusion of etoposide (VP-16) and carboplatin (CBDCA) administered continuously for 5 or 7 days. Because of the compatibility and solubility of the two agents, the treatment program could be administered on an outpatient basis. The dose rate of VP-16 was fixed at 30 mg/m2/day (total dose 150 mg/m2 for 5 days or 210 mg/m2 for seven days) for each cycle. Carboplatin was evaluated at three dose rates: 50, 60, and 75 mg/m2/day on the 5-day infusion and 40, 50, and 60 mg/m2/day on the 7-day infusion with cycles repeated at 28 to 42 days. The dose limiting toxicity was hematologic and followed a pattern typical for carboplatin, that is, delayed neutropenia and/or thrombocytopenia with a protracted leukocyte recovery. Renal toxicity was observed in three patients. The optimum total dose for the infusional carboplatin component was 300 mg/m2 (5-day) and 420 mg/m2 (7-day). The total etoposide dose was 150 mg/M2 and 210 mg/M2, which did not appear to contribute to the hematologic toxicity. Delivery of the admixture of VP-16 and CBDCA was feasible, although cumbersome, as a result of the portable delivery system. Extending the duration of infusion increases the total cumulative dose of carboplatin and etoposide that can be administered without increasing adverse effects.

Aged↗

A novel variant of growth hormone (GH) insufficiency following low dose cranial irradiation.

OBJECTIVE: We aimed to investigate the effect of low dose (1800 cGy) prophylactic cranial irradiation on physiological growth hormone secretion. DESIGN: We performed an analysis of 24-hour serum GH profiles using 20-minute sampling. PATIENTS: Forty-four children were studied, of whom 21 were long-term survivors of acute lymphoblastic leukaemia and 23 were normal children. They were further subdivided into prepubertal, pubertal and post-pubertal groups. MEASUREMENTS: GH profiles were analysed by autocorrelation, Fourier transformation and spectral analysis of stationarized data, and peak detection using the Pulsar peak detection program. RESULTS In the normal children, there was a significant increase in the median (range) area under the curve (AUC) of the GH profile between the prepubertal and pubertal groups (62 (11-124) and 137 (142-158) IU/I/h respectively, (P less than 0.01)). There was also a change in the spectral analysis through puberty. The dominant frequencies were spread widely in the prepubertal and post-pubertal groups but sharply focused in the pubertal group. In the cranially irradiated children there was no significant increase in AUC between the prepubertal (62(13-110) IU/I/h) and pubertal groups (92 (14-163) IU/I/h). The wide range of dominant frequencies persisted in the pubertal cranially irradiated group due to the presence of additional high frequency pulses. The impression of a disturbance of the periodicity of GH secretion in the cranially irradiated pubertal group was further supported by the finding that the autocorrelation function in this group alone was not significantly different from that which would arise from random data. CONCLUSIONS: A novel form of GH insufficiency has been observed after low dose irradiation in childhood in which an abnormality of periodicity and a quantitative reduction in GH secretion appears restricted to puberty.

Adolescent↗

Separation of factors required for cleavage and polyadenylation of yeast pre-mRNA.

Cleavage and polyadenylation of yeast precursor RNA require at least four functionally distinct factors (cleavage factor I [CF I], CF II, polyadenylation factor I [PF I], and poly(A) polymerase [PAP]) obtained from yeast whole cell extract. Cleavage of precursor occurs upon combination of the CF I and CF II fractions. The cleavage reaction proceeds in the absence of PAP or PF I. The cleavage factors exhibit low but detectable activity without exogenous ATP but are stimulated when this cofactor is included in the reaction. Cleavage by CF I and CF II is dependent on the presence of a (UA)6 sequence upstream of the GAL7 poly(A) site. The factors will also efficiently cleave precursor with the CYC1 poly(A) site. This RNA does not contain a UA repeat, and processing at this site is thought to be directed by a UAG...UAUGUA-type motif. Specific polyadenylation of a precleaved GAL7 RNA requires CF I, PF I, and a crude fraction containing PAP activity. The PAP fraction can be replaced by recombinant PAP, indicating that this enzyme is the only factor in this fraction needed for the reconstituted reaction. The poly(A) addition step is also dependent on the UA repeat. Since CF I is the only factor necessary for both cleavage and poly(A) addition, it is likely that this fraction contains a component which recognizes processing signals located upstream of the poly(A) site. The initial separation of processing factors in yeast cells suggests both interesting differences from and similarities to the mammalian system.

Base Sequence↗

Nutrition of the elderly.

The progressively increasing number of elderly people in the Canadian population and the disproportionate expenditure on their health care has stimulated interest in prevention of common illnesses observed in this age group. It is now recognized that nutrition plays an important role in health status, and both undernutrition and overnutrition are associated with greater risk of morbidity and mortality. Nutritional problems in the elderly can be suspected if there are several high-risk factors present--for example, living alone, physical or mental disability, recent loss of spouse or friend, weight loss, use of multiple medications, poverty, and high consumption of alcohol. Physical examination, anthropometry, and measurements of serum albumin levels and hemoglobin and lymphocyte counts are simple but helpful tools in confirming the presence of nutritional disorders. The prevention and correction of nutritional problems is likely to prove beneficial in the management of common geriatric illnesses. In these efforts, it is desirable to have a team approach in which the physician, the dietitian and the nurse each have a defined interactive role. Home care support services are important adjuncts in continuing care. Nutrition should receive a greater emphasis in the training of physicians and other health professionals.

Aged↗

Dual modulation of 5-fluorouracil using leucovorin and hydroxyurea. A phase I trial.

Oral hydroxyurea (HU) was added to a regimen of 5-fluorouracil (5-FU) plus leucovorin (LCV) administered as a continuous 24-hour infusion for 14 days. A previous report of the 5-FU plus LCV infusion established optimal dosages of 200 mg/m2/d and 5 mg/m2/d, respectively, for each agent. Oral HU was added to the regimen in total dosages of 0.5 g/d, 1.0 g/d, 1.5 g/d, or 2.0 g/d. Twenty-two patients received a total of 45 courses of treatment. Stomatitis was the dose-limiting side effect; it occurred in 3 of 14 courses with HU at 0.5 g/d (21%) and 9 of 17 courses with HU at 1.0 g/d (53%). Dosage escalation to 1.5 g/d or 2.0 g/d was possible in only 3 of 22 patients (17%). The median time to stomatitis was 10 days (range, 7 to 12 days). One response was observed in this heavily pretreated population. Phase II trials of HU plus LCV dual modulation of infusional 5-FU should use initial HU dosages of 0.5 g/d for the 14-day regimen described, with dose escalation as tolerated. Variable oral absorption presumably accounts for the small group of patients who can tolerate the higher doses of HU.

Administration, Oral↗

Infusional carboplatin. Phase I studies of 5-day and 14-day infusions.

Twenty-two courses of carboplatin (Paraplatin; Bristol-Meyers, Evansville, IN) (CBDCA) were administered to 15 patients with advanced cancer on a continuous 24-hour per day infusion schedule for either 5 days or 14 days. The objective of the trial was to establish the optimal dose rate and cumulative dose for this treatment schedule. The dose-limiting toxicity was myelosuppression, with leukopenia and thrombocytopenia observed. The optimal dose rate for the 5-day infusion was 75 mg/m2/d or a total cumulative dose of 375 mg/m2/d. The optimal dose rate for the 14-day infusion was 25 mg/m2/d or a total cumulative dose of 350 mg/m2/d. The times to nadir levels of leukocyte and platelet counts were 34 days and 25 days, respectively, with a median time to recovery of 14 days and 7 days, respectively, in patients with Grade 3 or greater marrow suppression. The pattern of hematologic toxicity with infusional CBDCA is comparable to that seen with bolus schedules. There is, therefore, no clinical advantage of the infusional schedule for CBDCA in terms of toxicity and the dose delivered per cycle, and the dose intensity is slightly less than with a bolus schedule. If there is a therapeutic advantage for the infusional schedule, a prospective comparative trial against the standard bolus schedule will be required to establish it. Bolus and infusional schedules for CBDCA are associated with a delayed pattern of thrombocytopenia and prolonged leukopenia, necessitating 5 or more weeks between treatment cycles.

Aged↗

Low incidence of non-A, non-B post-transfusion hepatitis in London confirmed by hepatitis C virus serology.

To see whether the introduction of screening tests for post-transfusion non-A, non-B hepatitis (NANBH) in the UK would be worth while, the incidence of such hepatitis was assessed among patients receiving blood during operations at five hospitals served by the North London Blood Transfusion Centre. 387 patients, who each received blood or blood components from an average of 3 donors were followed up prospectively and blood samples were taken every 2 weeks for 3 months and then each month for a further 3 months. 229 patients also provided a sample at 12 months. All available patient and donor samples were tested for alanine aminotransferase concentrations and for antibody to hepatitis C virus (anti-HCV) by ELISA. Repeatedly anti-HCV positive samples were submitted to supplementary HCV assays. 1 of the 387 patients showed biochemical evidence of acute post-transfusion NANBH after exclusion of non-viral causes. Anti-HCV developed in this patient and the seroconversion was confirmed by recombinant immunoblot assay and polymerase chain reaction. Serum from 1 of the 8 donors whose blood he received was positive for anti-HCV by all three methods. In another patient HCV seroconversion was shown by ELISA but alanine aminotransferase concentrations remained normal throughout follow-up. His samples and those of his 2 donors were negative for HCV by the polymerase chain reaction. A third patient showed rises in alanine aminotransferase compatible with post-transfusion NANBH, but serology and polymerase chain reaction assays for HCV were negative for her samples and those of her donors. Anti-HCV reactivity likely to be false positive (negative by both confirmatory tests and no adverse effects in recipients) was seen in 6 of 1283 donors. This study, despite its being carried out in the part of the UK with the highest frequency of infectious markers in blood donations, has shown a very low incidence of post-transfusion NANBH.

Acute Disease↗

Ifosfamide continuous infusion without mesna. A phase I trial of a 14-day cycle.

Twenty patients received 27 courses of ifosfamide administered as a 24-hour continuous infusion for 14 days without Mesna. The goal of the study was to deliver a dose rate and total cumulative dose of ifosfamide that would be comparable to standard bolus or short-term infusions administered with Mesna. Dose escalations proceeded from 200 to 300, 400, 450, 500, and 550 mg/m2/d. Four patients developed transient microscopic hematuria at 400, 450, and 500 mg/m2/d. There were no instances of macroscopic hematuria. At 550 mg/m2/d, three patients experienced nonurologic toxicity; confusion (1), nausea (1), and Grade 2 leukopenia (1). The recommended dose of 500 mg/m2/d delivers a total dose of 7 g/m2 per cycle, which is comparable to that delivered in clinical practice for bolus or short-term infusion. Because few patients received multiple courses over time, the cumulative effects are indeterminate in the present trial. The frequency and predictability of hematuria are not precise, and at least daily monitoring by urine Hematest is essential, adding Mesna to the infusate in patients with persistent hematuria. The protracted infusion schedule for ifosfamide permits convenient outpatient administration without Mesna and reduces the drug cost of clinical usage of this agent by up to $890 per cycle. Clinical activity was demonstrated in a single patient, but a comparative trial of standard bolus schedules with the protracted infusion schedule will be necessary to determine if the clinical effectiveness of the drug is maintained.

Adult↗

The application of hybrid mass spectrometry/mass spectrometry and high-resolution mass spectrometry to the analysis of fish samples for polychlorinated dibenzo-p-dioxins and dibenzofurans.

A hybrid mass spectrometer operated in low-resolution selected decomposition monitoring (SDM) mode was used for the analysis of whole fish samples for the 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins and poly-chlorinated dibenzofurans (PCDD/Fs). These fish samples were previously analyzed for PCDD/Fs using a high-resolution mass spectrometer following EPA protocols. The hybrid tandem mass spectrometric method using loss of COCl gave similar quantification results to those obtained by high-resolution mass spectrometry and eliminated the interferences attributed to polychlorinated biphenyls that were encountered in the high-resolution mass spectrometric analysis. Comparison of the two methods shows that the high-resolution mass spectrometric method surpasses the tandem mass spectrometric method in other analytical figures of merit, such as detection limit, linearity and reproducibility.

Animals↗

Interaction between cytochrome C and di- and tripeptides.

By observing changes in the absorbance spectrum between 340 and 650 nm, we found that tyrosyltyrosylphenylalanine (TTP) interacts with cytochrome C (CC). TTP caused the characteristic changes of CC reduction, namely, an increased optical density at 524 and 550 nm and a hyperchromic shift at 416 nm. The apparent dissociation constant (Kd) was 2.9 x 10(-3) M. Most of the reducible CC at 20 uM concentration was reduced by 10 mM TTP. TTP was more potent than all other peptides tested, including the previously reported tyrosylphenylalanine. That the carboxyl terminal phenyl group was essential for reduction was shown by comparing variously substituted di- and tripeptides. Reduction by TTP increased with increasing pH and buffer concentration at constant pH. A combination of superoxide dismutase and catalase failed to inhibit the reduction. We found no effect of TTP on O2 consumption of isolated intact mitochondria. Our data demonstrate that small peptides can serve as probes of the topography and electron density of CC and that the TTP-CC interaction may provide insight as an analog of in-vivo processes.

Amino Acid Sequence↗

Infusion of floxuridine plus etoposide plus cisplatin in human malignancies.

36 patients with advanced malignancy were studied in a phase I trial of continuous 24-h infusion of floxuridine (FUdR) plus etoposide plus cisplatin (FEP) administered for 5 consecutive days at 4-week intervals. Study design fixed the dose rate of etoposide and cisplatin with escalation of FUdR only. Dose rate-limiting toxicity related to the FUdR component was stomatitis and diarrhoea and was invariably associated with leukopenia and thrombocytopenia when grade 3 or 4 level gastrointestinal toxicity was observed. Only 3 of 64 courses were associated with transient renal failure related to cisplatin. Drug-related deaths occurred (leukopenia-associated sepsis) in 4 patients with poor performance status (ECOG 3 and 4). Responses occurred in 15 of 26 evaluable patients (all previously treated minimally or untreated) including 5/11 non-small cell lung cancer; 3/3 oesophageal; 2/2 breast; 4/5 gastric; 1 osteogenic sarcoma; and 1 unknown primary (probably ovary). The recommended dose rates for a 5-day infusion of the three agents for good risk patients is 20 mg/m2 per day of each drug. For poor risk patients including age greater than 65 years; performance status 2 or greater; or extensive bone metastases or prior radiation; the recommended starting dose rates are: FUdR 15 mg/m2 per day; etoposide 15 mg/m2 per day; and cisplatin 20 mg/m2 per day. Dose escalation of FUdR to a maximum of 25 mg/m2 daily is feasible in selected patients demonstrating optimal tolerance.

Adult↗

Episodic ACTH and cortisol secretion in normal children.

The aim of this study was to determine the normal relationship between ACTH and cortisol secretion in children. Fourteen children (nine male, five female; median age 11.3 years) were hospitalized and blood samples were taken every 20 min for 24 h. A circadian rhythm was observed with median 0900 h and midnight ACTH values of 1.80 and less than 0.97 pmol/l, and for cortisol 296 and 62 nmol/l respectively. The median (range) areas under the curve for ACTH and cortisol were 29.7 (9.0-53.8) pmol/l/h and 5114 (3562-8630) nmol/l/h respectively. There were no significant differences detected for ACTH and cortisol secretion between males and females, or between prepubertal (n = 9) and pubertal subjects (n = 5). Using a novel form of time series analysis we have shown that both ACTH and cortisol are secreted with a dominant periodicity of 0.7-1.0 h, representing 24-34 secretory episodes of ACTH and cortisol in 24 h. For cortisol, but not ACTH, there is a significant secondary periodicity of 2-3.2 h. To look for shared periodicities we have used the technique of coherency. This reveals that for six of the children ACTH and cortisol are secreted with a significant shared periodicity of 0.8-1.0 h, and for a further five children a similar secondary shared periodicity is present. Therefore in normal children ACTH and cortisol secretion are interdependent and episodic but are not influenced by either pubertal status or gender.

Adolescent↗

Interleukin-1 alpha-induced changes in androgen and cyclic adenosine 3',5'-monophosphate release in adult rat Leydig cells in culture.

Interleukin-1 (IL-1) has been proposed as a paracrine regulator of testicular function. The effect of this cytokine on adult rat Leydig cells in primary culture was investigated. Interstitial cells were purified on a two-step Percoll gradient and cultured in the presence or absence of recombinant human IL-1 alpha (IL-1 alpha). The presence of IL-1 alpha in the culture media resulted in a dose-dependent increase in 24-h basal androgen release (half-maximal effective concentration = 40-50 U/ml). The stimulatory effect of IL-1 alpha peaked on days 3 and 4, and was often still significant after 6 days of culture. Removal of IL-1 alpha was followed by a return of basal androgen release to control levels within 3 days. In contrast, cells treated with IL-1 alpha (100 U/ml) for 3 days released significantly less androgen (per 4 h) in response to 1-100 ng LH/ml than control cells. A similar inhibitory effect on the response to dibutyryl cAMP and pregnenolone was observed. Under basal conditions, IL-1 alpha-treated cells released significantly more cAMP than did control cells. In contrast, the increase in cAMP release seen with LH-stimulated cells was significantly inhibited by treatment with IL-1 alpha. These results suggest that IL-1 alpha has a dual effect on adult rat Leydig cells in culture. It stimulates basal but inhibits LH-induced androgen release with parallel changes in cAMP levels. An additional inhibitory effect appears to lie at the level of the 17 alpha-hydroxylase/C17-20 lyase enzyme.

Androgens↗

Anatomic location and variety of nonmalignant neck masses seen in surgical practice.

During a 10-year interval, 189 patients, comprised of 121 females and 68 males ranging in age from 1 to 98 years, were surgically treated for nonmalignant neck masses. Nonmalignant neck masses were located in the thyroid or submaxillary gland in 60 per cent of these patients. Thyroid adenoma, reactive cervical nodes, and mixed tumor of the submaxillary salivary glands represented the three most commonly occurring nonmalignant pathologic conditions in this series. When stratified by age and sex, thyroid abnormalities, specifically thyroid adenoma, occurred most often in females of all ages. In males, reactive nodes were usually seen before 40 years of age; thereafter, tumors of the submaxillary salivary gland predominated. Most studies of nonmalignant neck masses indicate that reactive nodes are the most common condition in patients of all ages. Thyroid conditions were seen most frequently in this group of patients. The probable explanation is a tertiary referral pattern to surgeons. Patients with nonsurgical conditions were, presumably, identified and managed earlier and not referred further, and therefore did not appear in this group of patients.

Adenoma↗

Comorbidity in the interpretation of dexamethasone suppression test results in children: a review and report.

The dexamethasone suppression test (DST) was administered as part of the initial clinical assessment to 83 children and adolescents who were consecutively referred for outpatient evaluation. All diagnoses were made clinically by a child psychiatrist according to DSM-III criteria. A weight-corrected dose of dexamethasone of 17 micrograms/kg was used. DSM-III diagnoses were made independent of DST results. Patients were stratified into four main diagnostic groups: major depressive disorder (MDD) (N = 27); attention deficit disorder with hyperactivity (ADDH) (N = 22); major depressive disorder plus attention deficit disorder with hyperactivity (MDD + ADDH) (N = 29); and psychiatric controls (PC) (N = 5). Rates of dexamethasone nonsuppression were found to be similarly elevated in children with MDD (29.6%), ADDH (22.7%), and MDD + ADDH (37.9%). All 5 psychiatric control patients had a normal postdexamethasone suppression (0%). A similar pattern of results emerged in a reexamination of the literature on available studies of DST in juveniles which revealed that children with major affective disorders, attention deficit disorder (ADDH), and anxiety disorders had comparable DST results that were significantly higher than the 5.6% rate found in normal controls. These findings provide further support for similarities in DST results between ADDH and MDD in outpatients. Although these results suggest a lack of specificity of the DST as a laboratory aid for the diagnosis of juvenile affective disorders, they are also consistent with findings indicating that the DST may be an index of clinical severity and other findings suggesting a possible association between ADDH and MDD. Despite its limitations, the DST may provide potentially useful clinical and research information regarding the pathophysiology of psychiatric disorders and in alerting clinicians to the presence of serious psychiatric disorders. The findings also stress the relevance of assessing comorbidity in interpreting DST results.

Adolescent↗

Antibody response to P-protein in patients with Branhamella catarrhalis infections.

Branhamella catarrhalis is now recognized as an important cause of lower respiratory tract infections, especially in the elderly. In most instances, pathogenicity is presumed by recovery of the organism in a sputum culture, a method that is less than conclusive. In order to better diagnose B. catarrhalis infections, an enzyme-linked immunoassay has been developed using P-protein as antigen to measure antibodies to B. catarrhalis. In 17 elderly patients with B. catarrhalis pneumonia and 12 with tracheobronchitis, acute-phase serum antibody titers to P-protein were found to be significantly increased when compared with those of normal subjects (both p less than 0.02). There were no differences in antibody titers between patients with pneumonia and tracheobronchitis. Antibody titers of convalescent-phase sera increased over those of acute-phase sera in 46 percent of pneumonia patients and 50 percent of tracheobronchitis patients. The results demonstrated that lower respiratory tract infections with B. catarrhalis promote a significant elevation in antibody response to P-protein of B. catarrhalis.

Aged↗