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Biomedical subjects

C Matthews

Publications and source records attributed to C Matthews.

At least 55 records · Page 3Linked to original sources
PubMed1992

The variability in circadian phase and amplitude estimates derived from sequential constant routines.

Both the constant routine (CR) and the dim light melatonin onset have been suggested as reliable methods to determine circadian phase from a single circadian cycle. However, both techniques lack published studies quantifying the intercycle variability in their phase resolution. To address this question eight healthy male subjects participated in two CRs, 7 days apart. Circadian phase was determined using 3-min samples of core body temperature and two hourly urinary sulphatoxy melatonin excretion rates. Phase and amplitude were estimated using simple (24 h) and complex (24 + 12 h) cosinor models of temperature data and the onset, offset, and a distance-weighted-least-squares (DWLS) fitted acrophase for the melatonin metabolite. The variability in phase estimates was measured using the mean absolute difference between successive CRs. Using the simple 24 h model of temperature data, the mean absolute phase difference was 51 min (SD = 35 min). Using the complex model, the mean absolute phase difference was 62 min (SD = 35 min). Using the DWLS fitted acrophase for the melatonin metabolite, the mean absolute phase difference between CR1 and CR2 was 40 min (SD = 26 min). The results indicate that for CRs a week apart, the mean absolute difference in an individual's phase estimate can vary by 40-60 min depending on the choice of dependent measure and analytic technique. In contrast to the intraindividual variability, the group results showed considerably less variability. The mean algebraic difference between CRs, using temperature- or melatonin-derived estimates, was less than 5 min, and well within the range of normal measurement error.

Adult↗
PubMed1991

Serial processing and the "phonetic route:" lessons learned in the functional reorganization of deep dyslexia.

A patient with chronic agrammatic Broca's aphasia presented with symptoms of deep dyslexia, in which it is presumed that phonologic processing of the written message is disrupted. Functional reorganization of the "nonlexical" or phonetic route of reading was undertaken according to principles of A. R. Luria, whereby the patient must learn consciously to control behaviors that had formerly been unconscious and automatic. This patient's responses in treatment made it clear that the phonetic route encompasses at least two dissociable functions, grapheme-phoneme conversion and sequential analysis. This is discussed in light of Luria's ideas regarding the functions of the precentral and postcentral regions of sensori-motor cortex.

Adult↗
PubMed1990

Direct electrophysiological actions of pentobarbital at concentrations achieved during general anesthesia.

Pentobarbital and alpha-chloralose are widely used for experimental anesthesia, but their direct electrophysiological actions at anesthetic concentrations are unknown. Trough and peak concentrations measured by high-performance liquid chromatography averaged 27 +/- 3 and 45 +/- 13 mg/l (means +/- SD) for pentobarbital and 41 +/- 15 and 103 +/- 13 mg/l for alpha-chloralose in dogs receiving them for general anesthesia. The direct effects of each agent on papillary muscle action potentials obtained from guinea pigs killed by decapitation were studied in vitro. Pentobarbital increased action potential duration to 95% by 24 +/- 6 and 33 +/- 4% at 25 and 50 mg/l (P less than 0.001 for each), respectively, and caused corresponding increases in effective refractory period. Furthermore, pentobarbital reduced maximum rate of voltage change (Vmax) of phase 0 in a voltage-, rate-, and concentration-dependent fashion, suggesting use-dependent sodium channel blocking actions. The voltage dependence of Vmax was shifted by 3.7 +/- 1.7 (P less than 0.01) and 6.5 +/- 1.8 mV (P less than 0.001) by 25 and 50 mg/l pentobarbital, respectively. In canine ventricular muscle, pentobarbital caused rate- and concentration-dependent decreases in Vmax and increases in action potential duration and refractory period over a concentration range of 5-100 mg/l. alpha-Chloralose was devoid of direct electrophysiological effects in both species. We conclude that pentobarbital has potentially important electrophysiological actions on ventricular tissues at concentrations required for general anesthesia and may confound the results of in vivo studies.

Anesthesia, General↗
PubMed1990

The immunosuppressive action of FK506. In vitro induction of allogeneic unresponsiveness in human CTL precursors.

FK506 is an unusually potent new immunosuppressive agent that inhibits T cell-mediated immunity in vivo and in vitro. In these studies we sought to further elucidate the immunosuppressive mechanism of action of FK506 on human allogeneic MLR-induced CTL activation. FK506 induced suppression of cell-mediated lympholysis by PBMC was optimal at 1-2-nM concentrations, if added at the initiation of 6 day CML cultures. The sensitivity to suppression decreased with time, and fully differentiated effectors were resistant to inhibition by FK506. Suppression of CML was not reversed by washing the cultures, adding exogenous IL-2, or restimulating with fresh cells. Pretreatment of unfractionated or adherent allogeneic PBMC with FK506 blocked the stimulating activity of these cells. Furthermore, addition of FK506-treated stimulator cells to cocultures containing untreated responder and stimulator cells resulted in suppression of CML. The inhibition in the cocultures was greatest if the FK506-pretreated cells were autologous to the original stimulator, suggesting a relative specificity in the suppression obtained under these conditions. These studies suggest that, in addition to suppressing the response of alloreactive CTL precursors, FK506 reduces the ability of irradiated allogeneic PBMC to induce CTL generation.

Anti-Bacterial Agents↗
PubMed1989

The significance of oncogene amplification in primary breast cancer.

Alterations in the gene copy numbers of the proto-oncogenes HER2/neu and c-myc in primary human breast cancer investigated in 73 patients. We detected amplification of HER2/neu in 17 patient samples and amplification of c-myc in 11, while amplification of both was seen in 6 samples. There was no correlation of age, hormone receptor positivity or tumour size with amplification of either proto-oncogene. Amplification of HER2/neu was significantly correlated with the stage of the disease. HER2/neu amplification was observed in 18.5% and 38% of node-negative and node-positive patients, respectively; the association between HER2/neu amplification and advanced stage of the disease was statistically significant (p = 0.05). Since this is a prospective study, the clinical significance of oncogene amplification is not known. The relatively high frequency of HER2/neu amplification points to a functional role in human breast cancer, particularly in the progression of the disease. The method used in our study allows oncogene amplification to be studied in conjunction with hormone receptor determination and thus may be of value in large clinical trials to determine the significance of oncogene abnormalities in breast cancer.

Breast Neoplasms↗
PubMed1989

Concentration dependence of class III and beta-adrenergic blocking effects of sotalol in anesthetized dogs.

Sotalol is unique among beta-adrenergic blocking drugs in possessing significant class III antiarrhythmic actions. The present study was designed to assess the relative concentration dependence of beta-blocking and class III actions of sotalol and to relate the findings to concentrations achieved during oral sotalol therapy in humans. Measurements were made in anesthetized dogs under control conditions, and then in the presence of a series of stable sotalol plasma concentrations produced by sequential loading and maintenance infusions. Beta-blocking effects of sotalol, determined by attenuation of the chronotropic actions of isoproterenol, were seen at the lowest dose used. Increases in atrial and ventricular refractory periods (observed in dogs with autonomic blockade to exclude beta-receptor-mediated or reflex autonomic effects) required much larger doses of sotalol. Half-maximal beta-blocking effects occurred at an average sotalol concentration of 0.8 +/- 0.3 mg/liter, an order of magnitude lower than the concentrations required for half-maximal effects on atrial (6.9 +/- 1.2 mg/liter, p less than 0.01) and ventricular (6.8 +/- 2.8 mg/liter, p less than 0.05) refractoriness. These results show that substantially higher concentrations are needed for the class III effects of sotalol than for its beta-blocking action. These pharmacodynamic differences need to be considered in evaluating the antiarrhythmic efficacy and mechanisms of this unusual drug.

Adrenergic beta-Antagonists↗
PubMed1989

Rapid reduction of severe asymptomatic hypertension. A prospective, controlled trial.

Rapid reduction of severe asymptomatic hypertension with orally administered antihypertensive medication has become a common emergency department practice. To determine if antihypertensive loading prior to initiation of maintenance therapy improved or hastened blood pressure control, 64 asymptomatic patients with severe hypertension were randomized to treatment with (1) hourly doses of clonidine hydrochloride followed by maintenance therapy (group 1); (2) an initial dose of clonidine followed by hourly placebo and subsequent maintenance therapy (group 2); or (3) maintenance therapy without prior loading (group 3). There was no difference between groups 1 and 2 in the time required to achieve acceptable blood pressure control during loading therapy, nor was there a difference at 24 hours in pressure reduction between groups 1,2, or 3. Further follow-up in 44 of these patients at 1 week demonstrated adequate control of systemic blood pressure in all groups, but no difference between groups. In view of the small but reported risk of antihypertensive loading and the burden and expense of prolonged emergency department therapy, these results suggest that the common practice of acute oral antihypertensive loading to treat severe, asymptomatic hypertension should be reconsidered.

Administration, Oral↗
PubMed1988

N-myc amplified in retinoblastoma cell line FMC-RB1.

A recently described retinoblastoma cell line, FMC-RB1, showed a 16-fold N-myc oncogene amplification. The patient from whom the cell line was obtained died from an aggressive disease. It is suggested that N-myc amplification may be an adverse prognostic indicator.

DNA Restriction Enzymes↗
PubMed1988

Wiskott-Aldrich syndrome in identical twins: abnormality of CD4 and CD8 positive lymphocytes.

The rare occurrence of Wiskott-Aldrich syndrome (WAS) in identical twin brothers without a preceding family history of the disease is described. Investigation into the nature of the lymphocyte abnormality in the surviving twin suggests that the frequency of T cell clone forming cells is markedly decreased. Further analysis of the T cell clones showed a deficiency of CD8 positive cytotoxic/suppressor cells. This alteration may be an underlying mechanism in the development of some of the clinical manifestations of WAS.

Antibodies, Monoclonal↗
PubMed1987

Mutation rate of normal and malignant human lymphocytes.

The genetic stability of normal and neoplastic lymphocytes was compared by using base-line mutation frequency and mutation rate/cell generation. Mutations at the hypoxanthine-guanine phosphoribosyltransferase locus were studied by enumerating thioguanine-resistant cells in a clonogenic assay. The base-line ("spontaneous") mutation frequency was 1.52 X 10(-6), 6.38 X 10(-6), and 1.06 X 10(-6) for normal cells from three individuals and was 1.16 X 10(-3), 6.08 X 10(-5), and 3.06 X 10(-5) for the three malignant cell lines, Jurkat (JM), HRIK, FMC-Hu1B, respectively. The mutation cell/generation rate was 24.6 X 10(-8), 15 X 10(-8), and 5.5 X 10(-8) for lymphocytes from the three normal individuals, and 666.4 X 10(-8), 52.8 X 10(-8), and 131 X 10(-8) for the three malignant cell lines. The results suggest that neoplastic lymphocytes are more genetically unstable than normal lymphocytes.

Burkitt Lymphoma↗
PubMed1987

Bevantolol disposition in patients with hepatic cirrhosis.

Bevantolol is a new, cardioselective beta-receptor antagonist that undergoes extensive hepatic biotransformation. To evaluate changes in the disposition of bevantolol produced by liver disease, a single 200-mg oral dose of bevantolol was administered in ten patients who had hepatic cirrhosis and to ten age-matched controls. Cirrhotic patients had a greater plasma bevantolol half-life (6.9 +/- 4.0 hr, mean +/- SD) then did patients with normal liver function (2.8 +/- 1.1 hr, P less than .01), and they also had a longer duration of significant bevantolol-induced heart rate slowing (for 12 hours after oral dose in cirrhotics versus three hours for controls). On the other hand, the peak concentration after the oral dose and the magnitude of bradycardiac effect were similar for both groups. Plasma bevantolol half-life was more variable in cirrhotic patients than in controls. Some of this variability among cirrhotics was attributable to age, which was a significant determinant of bevantolol half-life in the cirrhotic (but not in the control) patient sample. These results indicate that hepatic cirrhosis alters the disposition of bevantolol and suggest that modifications in bevantolol dose should be considered when using this drug to treat patients with liver disease.

Adrenergic beta-Antagonists↗
PubMed1987

In vitro cytotoxic drug sensitivity of human normal and malignant lymphocyte-clone-forming cells.

Cytotoxic drug sensitivity of normal human lymphocytes and malignant lymphocytes was estimated by a clonogenic method. Malignant T and B lymphocytes were relatively more sensitive than normal T lymphocytes to vincristine and Adriamycin. Since no plateau was observed in the clone survival with associated increasing drug concentration, spontaneous mutants could not be detected. It is suggested that the resistance to "natural product" drugs such as vincristine arises from induced mutations and not from the selection of already existing spontaneous mutants.

Burkitt Lymphoma↗
PubMed1987

Epilepsy surgery improves regional glucose metabolism on PET scan. A case report.

A patient with medically intractable complex partial epilepsy was evaluated for epilepsy surgery by electro-encephalograph recording with depth electrodes and 18F-fluorodeoxyglucose positron emission tomography (PET). A small calcified arteriovenous malformation was excised from the left parietal lobe, and the patient became seizure free. Baseline and language stimulation PET scans were obtained preoperatively and 10 months postoperatively. There was a significant increase in glucose metabolism of the left temporal lobe postoperatively, which we interpret as evidence of improved neuronal function. We suggest that this case represents evidence for a functional, and reversible, inhibition of neuronal metabolism by epileptic activity.

Cerebral Cortex↗
PubMed1987

Calcitriol, parathyroid hormone, and accumulation of aluminum in bone in dogs with renal failure.

Accumulation of aluminum in bone is a frequent finding in patients requiring chronic dialysis and is associated with considerable morbidity and/or mortality. Until now, evidence seemed to point to relatively low circulating levels of parathyroid hormone as a contributing factor, but because levels of parathyroid hormone and calcitriol are interrelated, calcitriol might be also involved. In this study we employed an animal model to evaluate the single and combined effects of parathyroid hormone and calcitriol on bone aluminum accumulation. The results show significantly less aluminum accumulation in calcitriol-replete dogs independent of the presence or absence of parathyroid hormone. These results indicate that low levels of calcitriol may play a role in the development of aluminum related bone disease. Further studies are needed to demonstrate whether administration of calcitriol in patients with renal insufficiency will prevent development of aluminum-related bone disease.

Aluminum↗