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Biomedical subjects

M Carroll

Publications and source records attributed to M Carroll.

At least 55 records · Page 3Linked to original sources
PubMed1999

A case-control assessment of risk factors for gallbladder carcinoma.

Gallbladder carcinoma is an uncommon, but highly fatal disease. Its symptoms frequently mirror those of gallstone disease, and in most instances, diagnosis is an incidental finding at surgery. While risk factors have been suggested for this cancer, many may in reality simply be a consequence of the older age of the population. This study is one of the few to approach this question by using a case-control study design comparing gallbladder carcinoma patients with a gallstone population, coupled with multivariate analysis to determine age-independent risk factors. Univariate analyses showed gallbladder carcinoma patients to be older than gallstone patients and to have many age-associated diseases. Following multiple regression adjustment for age, this disease was associated with female gender and with a previous history of gallstone symptoms. Carcinoma patients were less likely to have cholesterol gallstones in their gallbladders at surgery. A previous history of smoking was a substantial risk but of borderline statistical significance. Previous studies report associations that may be due to the older age of the gallbladder carcinoma patient. Our results show that after adjusting for age with multivariate analysis, gallbladder cancer subjects were predominantly female, more likely to report previous gallstone symptomology, and to smoke. While gallstones were not universally isolated from carcinoma patients at cholecystectomy, when present, they were less frequently classified as cholesterol gallstones based on visual inspection. Further cohort studies which target these populations will allow us to gain a more solid consensus on the risk factors for this disease.

Aged↗
PubMed1999

Altered distribution of intraglomerular immune complexes in C3-deficient mice.

We have studied the role of complement in a model of glomerular inflammation induced by the in situ formation of immune complexes along the glomerular basement membrane. In C3-deficient mice, produced by homologous recombination, immune complex formation occurs initially in the subendothelial site and progresses slowly to the subepithelial position, whereas wild-type mice do not develop subendothelial deposits. In addition, the accumulation of electron-dense deposits is greater in the complement-deficient mice. Complement therefore influences glomerular handling of immune complexes, possibly because of changes in the physiochemical characteristics of the immune complexes. However, despite evidence of complement activation in the wild-type mice, as demonstrated by immunohistochemical detection of C3, C4 and C9, the degree of proteinuria was similar in C3-deficient mice. We conclude that, although complement is required for the normal glomerular metabolism of immune complexes, other, complement-independent, factors are involved in the generation of glomerular injury in this model.

Animals↗
PubMed1999

The effect of text coherence and modality on metamemory judgements.

This study examined the effects of text coherence and modality on the metamemory judgements of Ease of Learning (EOL) and Judgement of Learning (JOL), and on the object-level measure of recall. Previous work found that sentence material set in a coherent, ordered text context was not judged as more memorable than that presented in a context of sentences in a disordered sequence, even though an ordered sequence helped recall (Shaddock & Carroll, 1997). The current study modified Shaddock and Carroll's design by changing the texts used from expository to narrative text. The metamemory judgements and recall were now found to be significantly more sensitive to material learned in an ordered sequence than to material learned in a disordered sequence. Also, JOLs and recall were more sensitive to material that was originally learned in an auditory mode (spoken presentation) than in a visual mode (verbal presentation). The results are discussed in terms of a cue-utilisation approach to metamemory judgements.

Adolescent↗
PubMed1999

Molecular and functional characteristics of a protective human monoclonal antibody to serotype 8 Streptococcus pneumoniae capsular polysaccharide.

The structural characteristics and biological activity of human antibodies that are reactive with the capsular polysaccharides of most serotypes of Streptococcus pneumoniae, including serotype 8, are unknown. This paper describes the generation, molecular structure, and protective efficacy of a human monoclonal antibody (MAb) reactive with the capsular polysaccharide of serotype 8 Streptococcus pneumoniae. We generated the immunoglobulin M(kappa) [IgM(kappa)] MAb D11 by Epstein-Barr virus transformation of peripheral lymphocytes from a Pneumovax recipient. Nucleic acid sequence analysis revealed that MAb D11 uses V3-15/V(H)3 and A20/V(kappa) gene segments with evidence of somatic mutation. In vitro studies revealed MAb D11-dependent complement deposition on the capsule of serotype 8 organisms via either the classical or the alternative complement pathway. In vivo, MAb D11 prolonged the survival of both normal and C4-deficient mice with lethal serotype 8 S. pneumoniae infection. Our findings demonstrate that a serotype-specific human IgM with certain structural and functional characteristics was protective in mice lacking a functional classical complement pathway and show that alternative complement pathway activation is an important determinant of pneumococcal protection.

Amino Acid Sequence↗
PubMed1998

Phase I trial of intraperitoneal iododeoxyuridine with and without intravenous high-dose folinic acid in the treatment of advanced malignancies primarily confined to the peritoneal cavity: flow cytometric and pharmacokinetic analysis.

In this Phase I study, the maximally tolerated doses (MTDs) of i.p. iododeoxyuridine (IdUrd) alone and in combination with i.v. calcium leucovorin (LV) were determined. The pharmacokinetics and pharmacological advantage of IdUrd were evaluated, and flow cytometric analysis allowed examination of the extent of incorporation of IdUrd into tumor cells with and without the addition of i.v. LV. Thirty-nine patients with advanced neoplasms primarily confined to the peritoneal space were enrolled in a dose-escalation trial using 4-h dwells of IdUrd administered i.p. daily for 4 days with and without an i.v. infusion of LV 500 mg/m2/day for 4.5 days. Twenty-three patients received single-agent therapy, and 13 patients received i.p. IdUrd in combination with i.v. LV. The MTD of single-agent IdUrd administered on this schedule was 4125 mg/m2/day for 4 days; and that of the IdUrd in combination was 3438 mg/m2/day. Dose-limiting toxicities were myelosuppression and stomatitis. During the period of the dwell, the peritoneal AUC (area under the curve) of IdUrd exceeded the plasma AUC of IdUrd by one or two orders of magnitude in all patients at all doses tested; there was a possible effect of LV on peritoneal AUC. The geometric mean pharmacological advantage (AUCperitoneal/ AUCplasma) was 181 at 625 mg/m2/day and 90 at 4538 mg/m2/day. Flow cytometric analysis suggests saturation of IdUrd measured in DNA at the 2500-3125 mg/m2 dose level, without an increase after the addition of LV. Twelve patients received 4-12 courses of therapy. One patient with recurrent ovarian cancer who received 16 courses of therapy experienced complete resolution of her ascites, near normalization of CA-125 levels, and improved quality of life; two patients with high-risk tumors receiving "adjuvant" therapy are disease-free at 3 and 6 years after treatment; other patients experienced transient clearing of ascites. The recommended Phase II dose of i.p. IdUrd using a 4-h dwell daily for 4 days is 3750 mg/m2/day alone or 3125 mg/m2/day in combination with continuous i.v. LV at 500 mg/m2/day for 4.5 days. Although flow cytometric data suggest that DNA incorporation of IdUrd is not affected by the addition of LV, the cytotoxicity of the combination regimen may be increased due to LV-enhanced, IdUrd-related inhibition of thymidylate synthase. For this reason, we recommend that efficacy studies of the combination continue in parallel with studies of IdUrd alone.

Adult↗
PubMed1998

Enhanced B-1 cell development, but impaired IgG antibody responses in mice deficient in secreted IgM.

The role of endogenous natural IgM in promoting the adaptive Ab response was investigated in newly constructed mutant mice in which B cells do not secrete IgM but still express surface IgM and IgD and undergo class switching to express other Ig isotypes. While the mutant mice had relatively normal numbers of conventional B (B-2) cells in all tissues examined, unexpectedly, B-1 cells in the peritoneum and spleen were approximately threefold more abundant. The elevated levels of B-1 cells were already detectable at 4 wk of age and were stably maintained throughout life. The levels of serum IgG2a, IgG3, and IgA were also elevated in the mutant mice at an early age. IgG2a response to a T cell-independent Ag was augmented, whereas IgG Ab responses to suboptimal doses of a T cell-dependent Ag were impaired. The latter defect was associated with fewer splenic germinal centers, impaired Ab affinity maturation, and less Ag trapping on follicular dendritic cells. Together, these findings demonstrate a physiologic role of natural IgM in the feedback regulation of B-1 cell development, the regulation of IgG2a production, and the promotion of efficient B-2 cell Ab responses.

Animals↗
PubMed1998

Awareness of remembering achieved through automatic and conscious processes in multiple sclerosis.

Fifty multiple sclerosis (MS) and forty-one matched control subjects were administered a word stem completion task and the California Verbal Learning. Test (CVLT). As predicted, priming in a conventional "implicit" task did not differ for MS and control groups, and under "explicit" instructions verbal list recall was significantly lower in the MS group with recognition intact. Application of the process dissociation procedure (Jacoby, Toth, & Yonelinas, 1993) to the word stem task demonstrated that conscious and unconscious processes both contribute to remembering in MS. Exploratory analyses found no group differences in words remembered under inclusion nor exclusion conditions, though preliminary estimates for MS automatic processing exceeded those for controls. As predicted, prospective metamemory judgments reflected subsequent performance for both groups in the inclusion but not the exclusion condition. By contrast, retrospective monitoring for both groups reflected memory performance in both conditions. However post hoc analyses demonstrated that those MS subjects who employed more automatic processing were less aware retrospectively of their successful remembering under exclusion than MS subjects who used less automatic processing.

Adult↗
PubMed1998

Comparison of rocuronium and suxamethonium for use during rapid sequence induction of anaesthesia.

This study was designed to compare the tracheal intubating conditions during a rapid sequence induction of anaesthesia using rocuronium 0.6 (n = 61) or 1.0 mg.kg-1 (n = 130) or suxamethonium 1.0 mg.kg-1 (n = 127) as the neuromuscular blocking drugs. Anaesthesia was induced with fentanyl 1-2 micrograms.kg-1 and thiopentone 5 mg.kg-1 (median dose) and intubating conditions were assessed 60s after the administration of the neuromuscular blocking drug by an observer unaware of which drug had been given. Intubating conditions were graded on a three-point scale as excellent, good or poor, the first two being considered clinically acceptable. The study was carried out in two parts. At the end of the first part a comparison between the two doses of rocuronium was carried out when at least 50 patients had been enrolled in each group. The results showed the intubating conditions to be significantly superior with the 1.0 mg.kg-1 dose of rocuronium (p < 0.01). Final comparison between the 1.0 mg.kg-1 doses of rocuronium and suxamethonium showed no significant difference in the incidence of acceptable intubations (96 and 97%, respectively). The incidence of excellent grade of intubations was, however, significantly higher with suxamethonium (80% vs. 65%; p = 0.02). It is concluded that rocuronium 1.0 mg.kg-1 can be used as an alternative to suxamethonium 1.0 mg.kg-1 as part of a rapid sequence induction provided there is no anticipated difficulty in intubation. The clinical duration of this dose of rocuronium is, however, 50-60 min.

Adolescent↗
PubMed1998

The agenda of the organization. 1: A framework.

It is difficult at times to know if the welfare and well-being of an organization is being best served by the individuals who make decisions on its behalf. Sometimes decisions made are driven more by the needs of individual persons rather than by the needs of the organization. Company politics, conflicts, work relationships, territory and turf, individual status and power and personality issues all influence what happens and how decisions are made. Major decisions in areas such as downsizing, re-organization and corporate strategy are often made by individuals. Do these decisions best suit the agenda of the organization or reflect the agenda of the individual? Who looks after the organizational agenda? Noer's (1993) model is used to illustrate how what is best for the organization, and not just individuals within it, can be attained.

Organizational Culture↗
PubMed1998

The agenda of the organization. 2: Interventions.

Many contemporary organizations, though doing well in productivity, are in chaos. Stress amongst managers and employees is still rampant and the assertion that 'people are our best assets' is confirmed more in words than in actions. What interventions are needed to best add value to the agenda of the organization and influence employee performance for the better? A philosophy of employee care includes looking at how managers take responsibility for performance management, deal with their own and others' stress and how the dynamics within organizations can be understood and harnessed for the welfare of the company. It also includes reviewing, articulating and implementing policies and systems that affect individuals in the organization and the organization as a whole.

Humans↗
PubMed1998

Cellular but not plasma pharmacokinetics of lometrexol correlate with the occurrence of cumulative hematological toxicity.

Lometrexol inhibits the first folate-dependent enzyme in de novo purine biosynthesis and is avidly polyglutamated and retained in tissues expressing folylpolyglutamate synthetase. Although clinical studies have been limited by cumulative toxicity, preclinical studies show that pretreatment with folic acid can protect normal tissue while maintaining tumor cytotoxicity. Therefore, a Phase I study of lometrexol every 21 days preceded by i.v. folic acid was initiated. Lometrexol was studied in six patients at 15 mg/m2, in six patients at 20 mg/m2, in three patients at 25 mg/m2, and in nine patients at 30 mg/m2. Patients received either 5 mg of folic acid 1 h before or 25 mg/m2 3 h before lometrexol. Blood samples were obtained around the first course and weekly thereafter for determination of plasma and erythrocyte (RBC) lometrexol concentrations. Bioactive folates in plasma and RBCs were determined in a subset of patients. Lometrexol pharmacokinetics were best described by a three-compartment model. Mean clearance and volume of distribution were 1.6 +/- 0.6 liters/h/m2 and 8.9 +/- 4.1 liters/m2. Mean half-lives were 0.23 +/- 0.1, 2.9 +/- 1.4, and 25.0 +/- 48.7 h. Pharmacokinetics were independent of either lometrexol or folic acid dose. In the weekly blood samples, RBC lometrexol levels rose, long after plasma lometrexol was undetectable. RBC lometrexol levels were independent of folic acid or lometrexol dose. Bioactive folates measured in plasma and RBCs during this same time period did not accumulate. Rising RBC levels were correlated with a fall in hematocrit, hemoglobin, and platelet count. This study indicates that the cumulative toxicity of lometrexol is related to tissue concentration and not plasma pharmacokinetics. RBC lometrexol may be an indicator of cumulative drug exposure and effect.

Antimetabolites, Antineoplastic↗
PubMed1998

The effect of a video character's smoking status on young females' perceptions of social characteristics.

Despite public warnings of the health risks associated with cigarette smoking, as well as advertising bans and educational programs in schools, the percentage of young females who smoke is on the rise. This study examined the effect of a video character's smoking status on young females' perceptions of social characteristics. University students were shown a video of a young woman in a socially oriented role-play. The video portrayed a smoker for the experimental group and a nonsmoker for the control group; in all other respects the video presentations were identical. Both groups answered a questionnaire pertaining to social characteristics they believed she possessed. The experimental group rated the character as more outgoing, more sophisticated, not as easy to manipulate, and less emotional about breaking up with her boyfriend than did the control group. There were no significant differences in ratings of her uncertainty in a crowd, her degree of unpopularity, her ability to be intimidated, the degree others admire her, and her attractiveness. The results are discussed in the light of previous studies, and implications for future research are explored.

Adolescent↗
PubMed1997

CGP 57148, a tyrosine kinase inhibitor, inhibits the growth of cells expressing BCR-ABL, TEL-ABL, and TEL-PDGFR fusion proteins.

CGP 57148 is a compound of the 2-phenylaminopyrimidine class that selectively inhibits the tyrosine kinase activity of the ABL and the platelet-derived growth factor receptor (PDGFR) protein tyrosine kinases. We previously showed that CGP 57148 selectively kills p210BCR-ABL-expressing cells. To extend these observations, we evaluated the ability of CGP 57148 to inhibit other activated ABL tyrosine kinases, including p185BCR-ABL and TEL-ABL. In cell-based assays of ABL tyrosine phosphorylation, inhibition of ABL kinase activity was observed at concentrations similar to that reported for p210BCR-ABL. Consistent with the in vitro profile of this compound, the growth of cells expressing activated ABL protein tyrosine kinases was inhibited in the absence of exogenous growth factor. Growth inhibition was also observed with a p185BCR-ABL-positive acute lymphocytic leukemia (ALL) cell line generated from a Philadelphia chromosome-positive ALL patient. As CGP 57148 inhibits the PDGFR kinase, we also showed that cells expressing an activated PDGFR tyrosine kinase, TEL-PDGFR, are sensitive to this compound. Thus, this compound may be useful for the treatment of a variety of BCR-ABL-positive leukemias and for treatment of the subset of chronic myelomonocytic leukemia patients with a TEL-PDGFR fusion protein.

Animals↗
PubMed1997

Heat shock protein 70 expression in native and heterotopically transplanted rat hearts.

Heat shock proteins (hsp) are intracellular proteins that are rapidly synthesized in response to a variety of stress factors. Recent studies in rats have shown that these proteins can elicit a lymphocyte response during cardiac allograft rejection. We studied the expression of the inducible (i) and constitutive (c) forms of hsp70 in rat cardiac allograft and isograft recipients to evaluate their utility as indicators of transplant rejection. Heterotopic transplantation of rat hearts was performed, using Lewis to Lewis isografts and ACI to Lewis allografts. Sham-operated rats were used as controls. Transplanted isograft, allograft, and native hearts of the transplant recipients and their livers and spleens were harvested at 5 days posttransplant and analyzed for hsp70 (i) and (c) expression by Western blots. Seven animals were studied in each group. Isografts at 3 and 60 days and allografts at 8 days were also studied. Quantification of band densities was carried out by laser densitometry. Physiological function of the native hearts of the transplant recipients was studied using Langendorff preparations. High levels of hsp70 (i) were noted in the transplanted and native hearts of the transplant recipients but not in their livers or spleens or in the hearts of the sham-operated control animals. Myocardial function of the native hearts of the transplant recipients was not significantly different from that of the controls. Significantly higher levels of hsp70 (c) were present in mild and severely rejecting allografts compared with controls and nonrejecting isografts. In the rat model of heterotopic cardiac transplantation, high levels of hsp70 (i) in the native hearts of the allograft and isograft recipients suggest a transplant-related, cardiac-specific stress process, not previously described. Heat shock protein 70 (c) expression is significantly increased during early and late allograft rejection and may serve as an indicator of transplant rejection.

Animals↗