Search PubMed⌕ Search

Biomedical subjects

M Buckley

Publications and source records attributed to M Buckley.

At least 19 recordsLinked to original sources
PubMed1995

Severe hemolytic anemia associated with the homozygous state for an unstable hemoglobin variant (Hb Bushwick).

We have investigated a 13-year-old girl from first cousin parents who presented with severe hemolytic anemia. Hematologic studies showed unstable hemoglobin (Hb) disease (chronic Heinz body anemia), and DNA analysis showed that the patient was homozygous for the previously reported abnormal Hb called Hb Bushwick (beta 74E18 gly-->val). Hb Bushwick is unstable in vitro and in vivo. In addition, using globin chain biosynthetic studies, we show that the beta (Bushwick) chains are unstable. Six members of the patient's family were heterozygous for Hb Bushwick and had a compensated hemolytic disorder. By contrast, the homozygous patient had chronic anemia caused by a combination of hemolysis and ineffective erythropoiesis that was subject to severe exacerbation concomitant with infection. Thus, although unstable Hb disease is correctly regarded as dominant, we clearly see a dosage effect in its expression, whereby the homozygous state is still compatible with life although the red blood cells contain nearly 100% unstable Hb.

Adolescent↗
PubMed1995

The prevalence and technical quality of endodontic treatment in an American subpopulation.

Few data have been collected regarding the prevalence and quality of root canal therapy in American populations. European studies of various populations were used as a model for the evaluation of the prevalence and technical standard of endodontic treatment in a patient group seen for screening at a United States dental school. Full-mouth radiographic series were examined for the presence of root fillings, periapical pathologic conditions, and coronal restorative status. The obturation density and length were also recorded. Of 5272 teeth examined, 5.5% had root fillings. Periapical disease was evident in 4.1% of all teeth and 31.3% of root-filled teeth. Lesser-quality root fillings were more strongly associated with periapical disease than were higher-quality obturations. In addition, only 42% of the obturations could be considered technically satisfactory. Such data suggests that more research must be directed toward the study of factors that affect treatment outcome.

Adult↗
PubMed1992

Evaluation of a stable CCK agonist (A68552) in conditioned avoidance responding in mice, rats, and primates: comparison with typical and atypical antipsychotics.

In a variety of in vivo and in vitro tests, cholecystokinin (CCK) has been shown to produce effects that would suggest a functional antagonism of dopamine. On that basis, it has been hypothesized that CCK could have antipsychotic effects. We compared the CCK agonist, A68552, to the antipsychotics haloperidol (HAL), clozapine (CLOZ) and sulpiride (SULP) in various forms of conditioned avoidance using rats, mice, and cynomolgus monkeys. In rats, HAL disrupted both acquisition of a conditioned shelf-jump avoidance response and performance of the response by previously trained animals. CLOZ and SULP were ineffective in suppressing performance by previously trained rats but blocked acquisition of the response. CLOZ disrupted avoidance responding on the first 3 of 4 consecutive days of acquisition. SULP significantly suppressed avoidance responding on the last 3 days and significantly increased escape failures on day 2. A68552 administered during acquisition failed to significantly suppress avoidance responding. In mice, both HAL and CLOZ blocked performance of two-way shuttle conditioned avoidance at doses (0.1 and 3.0 mg/kg, IP, respectively) that had no effect on escape responding. A68552 at doses up to 1.07 mg/kg IP had no effect on performance. Mice treated with A68552 during acquisition showed a mild but statistically significant suppression of avoidance and an equivalent suppression of escape responding. Cynomolgus monkeys trained in a conditioned avoidance procedure were sensitive to the disruptive effects of HAL at a dose of 0.03 mg/kg IM while A68552 was without significant effect at doses up to those producing emesis (0.214 mg/kg, IM). A68552 does not resemble either HAL or the "atypical" antipsychotics, CLOZ or SULP, in conditioned avoidance tests.

Animals↗
PubMed1992

Interferon alfa-2a and fluorouracil in the treatment of patients with advanced esophageal cancer.

PURPOSE: The trial was undertaken to determine the response rate to and toxicities from the combination of interferon alfa-2a (IFN) and fluorouracil (FU) in patients with advanced esophageal cancer. MATERIALS AND METHODS: In this prospective phase II trial conducted at a large tertiary referral cancer center and university hospital, 40 patients with advanced locoregional, metastatic epidermoid, or adenocarcinoma of the esophagus were given FU 750 mg/m2 by 24-hour continuous intravenous infusion days 1 to 5, followed by weekly outpatient bolus FU 750 mg/m2 and IFN 9 x 10(6) U three times per week from day 1. Dose was attenuated for fatigue, neurotoxicity, gastrointestinal toxicity, and myelosuppression. RESULTS: Complete and partial responses were seen in 10 of 37 assessable patients with esophageal cancer (27%; 95% confidence interval, 0.13 to 0.41). Although substantial, toxicity was tolerable and primarily involved fatigue and mild myelosuppression. The median duration of response was 6.4 months (range, 2.8 to 14+ months). CONCLUSION: The combination of IFN and FU is an active regimen in the treatment of advanced esophageal cancer with a response rate similar to that reported for cisplatin-containing combinations in similar patient populations. Further studies based on this combination are indicated.

Adenocarcinoma↗
PubMed1991

The role of oil and agalactosyl IgG in the induction of arthritis in rodent models.

The proportion of agalactosyl IgG [Gal(O)] is raised in human rheumatoid arthritis and tuberculosis. We report here that injection of pristane into the peritoneal cavities of mice on days 0 and 50, which is known to induce plasmacytomas and arthritis, also induced a rise in the proportion of Gal(O), correlating with a simultaneous rise in the level of IgG antibody binding to the 65-kDa heat-shock protein of Mycobacterium bovis (hsp65). Arthritis developed in a proportion of those CBA/Igb mice with the highest percentage of Gal(O). Pretreatment with 50 micrograms of recombinant mycobacterial hsp65 intraperitoneal (i.p.) on day -10, or with 500 rad irradiation on day -2 before the first of the two injections of pristane reduced the incidence of arthritis from 24% in control animals, to 5.3% and 0.4%, respectively. The reduced incidence of disease correlated with smaller rises in the % Gal(O) at 50-75 days, although levels at 150-200 days were not affected. The arthritogenic effect of oil was not confined to the pristane model, since a single i.p. injection of oil 21 days before immunizing DBA/1 mice with type II collagen reduced the mean day of onset of this arthritis, [which we have previously shown to correlate with raised % Gal(O)], from 38 to 15 days (p less than 0.001). One interpretation is that an autoimmunogenic stimulus, given when % Gal(O) is raised, is more likely to evoke disease. Since oil granulomata are known to secrete interleukin 6, which has B cell-regulatory properties and is secreted by rheumatoid synovial cells, we tested sera from interleukin 6-transgenic mice, and found a strikingly raised percentage of Gal(O). We suggest, therefore, that the role of oil in the induction of arthritis is the dysregulation of cytokine release of which a raised percentage of Gal(O) may be a direct or indirect consequence, associated with an increased susceptibility to autoimmunogenic stimuli.

Animals↗
PubMed1991

Treatment of acute promyelocytic leukaemia relapsing after allogeneic bone marrow transplantation with all-trans-retinoic acid: suppression of the leukaemic clone.

We describe the clinical experience of a male patient with acute promyelocytic leukaemia, relapsing after sex-mismatched allogeneic bone marrow transplantation and treated with all-trans-retinoic acid. Resolution of the coagulopathy was observed by day 7 of therapy. A complete remission was achieved by day 47 after a period of pancytopenia, dysplastic myeloid maturation and bone marrow hypocellularity with necrosis and fibrosis. Serial cytogenetic analyses revealed a progressive loss of the male leukaemic clone [46XY,t(15;17)] and emergence of normal female (donor) cells [46XX] which became completely dominant with remission. Adverse effects of all-trans-retinoic acid included bone pain and a prominent leucocytosis requiring leukaphereses and hydroxyurea therapy. All-trans-retinoic acid can induce complete remission of recurrent acute promyelocytic leukaemia following bone marrow transplantation. The data suggest that remission is due to differentiation and suppression of the leukaemic clone while allowing repopulation of the marrow with non-malignant cells.

Adult↗
PubMed1991

Fournier's gangrene of scrotum in a patient with AIDS.

Fournier's gangrene of the scrotum, a form of necrotising fasciitis, is a rare but potentially fatal disorder. Predisposing conditions include chronic alcoholism and diabetes mellitus, possibly as a result of impaired immunity. Fournier's syndrome, occurring in a patient with AIDS, is described.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Schizophrenia, bipolar disorder and depression. A discriminant analysis, using 'lifetime' psychopathology ratings.

Discriminant and canonical variate analyses were performed using 302 patients, on whom ratings of lifetime psychopathology and course of illness has been made. DSM-III diagnoses were used to form the criterion groups. Bipolar disorder emerged as a distinct grouping, but there are reasons for dissatisfaction with its definition. The remaining patients formed a 'schizodepressive continuum', but this also had a tendency to bimodality. It is possible that the distinction between schizophrenia and depression was obscured by inadequacies in the data and the inclusion of excessive numbers of patients with schizoaffective depression in this study.

Adolescent↗
PubMed1988

Alterations in aortic endothelial cell morphology and cytoskeletal protein synthesis during cyclic tensional deformation.

Previous studies have shown that bovine aortic endothelial cells (ECs) in culture respond to repetitive tensional deformation with an increase in deoxyribonucleic acid synthesis and cell proliferation. This study was designed to determine whether cyclic tensional deformation of ECs in vitro induces different morphologic or protein synthetic responses. ECs from passages 6 through 9 were seeded in 35 mm2 well silicone rubber plates at 2 x 10(5) cells/well and allowed to attach for 24 hours. The experimental group was placed in a vacuum-operated stress-providing device that exerted an elongation of 24% at maximum downward deflection of the culture plate bottom and was subjected to repetitive cycles of 10 seconds of 24% maximum elongation and 10 seconds of relaxation for 5 days. The control group was subjected to similar incubation conditions but without stretch. 35S-methionine (500 muCi/well) was added to the plates 24 hours before harvesting, and two-dimensional gels of the harvested lysates (isoelectric focusing with pH 3 to 10 ampholytes followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis on 12.5% gels) were performed and the labeled proteins visualized by autoradiography. The data indicate that there is a differential synthesis of proteins, with synthesis of some proteins decreased or ablated whereas other proteins were increased in response to cyclic mechanical tension. The actin filament organization was evaluated after staining with rhodamine phalloidin, a fluorescent F-actin probe. The ECs subjected to tension had a more polygonal shape and demonstrated pseudopods and actin stress fibers, whereas ECs cultured under static conditions were more rounded and did not express actin stress cables.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1986

Perioperative and long-term results after electrophysiologically directed ventricular surgery for recurrent ventricular tachycardia.

Thirty-six patients underwent ventricular aneurysmectomy and electrophysiologically directed endocardial resection for treatment of recurrent ventricular tachycardia refractory to antiarrhythmic drug therapy. The surgical mortality rate was 17% and all 30 patients discharged from the hospital were alive at the end of the follow-up period (range 6 to 54 months), yielding a cumulative projected survival rate of 83% by actuarial analysis. Poor systolic function of the nonaneurysmal ventricular segments was the strongest and the only independent predictor of operative mortality among the clinical, hemodynamic, angiographic and electrophysiologic variables analyzed by stepwise logistic regression. Ventricular tachycardia recurred early in four of the six patients in whom the endocardial resection was limited to a small area for technical reasons. Twelve patients, including 10 with sustained ventricular tachycardia still inducible by postsurgical programmed electrical stimulation, were discharged receiving antiarrhythmic drugs that had been tried unsuccessfully before surgery. During a mean follow-up period of 25 +/- 15 months, nonfatal sustained ventricular tachycardia recurred in two patients after discharge. Inadequate endocardial resection was a significant predictor of arrhythmia recurrence.

Actuarial Analysis↗
PubMed1985

Development of a method for rating cognitive responses to a diagnosis of cancer.

The development of a method for rating cognitive responses to the diagnosis of early breast cancer, lymphoma and Hodgkin's disease is described in the context both of recent coping theory and a previous study by this Unit relating outcome to response to diagnosis. The ratings are defined in a manual using simple language and avoiding assumptions about the functions of responses; examples are given.

Adaptation, Psychological↗