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Biomedical subjects

D Harrison

Publications and source records attributed to D Harrison.

At least 109 records · Page 6Linked to original sources
PubMed1990

Effects of truncal vagotomy and partial gastrectomy on the pharmacokinetics of propranolol enantiomers in dogs.

The effect of partial gastrectomy on the pharmacokinetic parameters of (+)- and (-)-propranolol were investigated in six dogs. (+/-)-Propranolol (3 mg/kg body weight) was administered orally before and after surgery and the plasma concentrations of (+)- and (-)-propranolol were determined using an indirect enantioseparation technique. There were significant differences (p less than or equal to 0.05, paired t-test) in the area under the concentration-time curves (AUCs) and the maximum plasma concentration (Cmax) between (+)- and (-)-propranolol. The ratio AUC(+):AUC(-) was 1.73 +/- 0.28. These differences between the enantiomers remained unchanged after surgery. Other pharmacokinetic parameters showed no stereoselectivity. After partial gastrectomy, there was a slight, but nonsignificant decrease in time to reach maximum plasma concentration (tmax) and in the absorption half-life for both enantiomers. The maximum plasma concentration increased slightly. The elimination half-life and the mean residence time remained unchanged before and after surgery. Therefore, it is unlikely that there are any clinically relevant changes in the pharmacokinetics of (+)- and (-)-propranolol after partial gastrectomy.

Animals↗
PubMed1990

Theophylline absorption and gastric emptying after partial gastrectomy in dogs.

The pharmacokinetic parameters of theophylline, administered orally as a solution (4 mg/kg body weight), were studied in six dogs before and after two different kinds of gastric surgery in which part of the stomach was removed. The theophylline absorption rate was slightly increased after this antrectomy, whereas other pharmacokinetic parameters, such as area under the concentration time curve (AUC) and the elimination half-life (t1/2), remained unchanged. Gastric emptying was quantified using radionuclide imaging; after antrectomy, it was accelerated for liquids and delayed for solids.

Animals↗
PubMed1990

Effect of aging on epidermal dendritic cell populations in C57BL/6J mice.

The density and function of epidermal dendritic cell populations were investigated in aged C57BL/6J mice. The densities of both Langerhans cells (LC) and Thy-1+ dendritic epidermal cells were found to decrease with age. Epidermal cell suspensions from aged mice showed impaired immunologic function as assessed in vitro by the skin-lymphocyte reaction assay and by measuring the ability of epidermal cell suspensions to stimulate the proliferation of sensitized T cells in the presence of the sensitizing antigen. However, the capacity of LC to transport antigen from the skin to the draining lymph nodes was found in vivo to be comparable to that of young mice. Results of transplantation of bone marrow cells from young and old donors into irradiated recipients indicate that the decreased Langerhans cell density found in old mice may result from a deficiency in Langerhans cell bone marrow progenitors.

Aging↗
PubMed1990

Ultrastructural localization of cytochrome b in the membranes of resting and phagocytosing human granulocytes.

Affinity-purified rabbit anti-neutrophil cytochrome b light or heavy chain antibodies were used to immunocytochemically and biochemically localize cytochrome b in neutrophils and eosinophils. The antibodies were monospecific, recognizing polypeptides of 91 and 22 kD, respectively, on Western blots of whole neutrophil extracts. The antibodies were used in Western blot analysis of subcellular fractions of purified neutrophils to confirm that the distribution of cytochrome b spectral absorbance matched that of the two subunits. Thin sections of cryofixed, molecular distillation-dried granulocytes were labeled with the anti-cytochrome b antibodies, followed by incubation with biotin-conjugated secondary antibody, and final labeling with streptavidin-conjugated colloidal gold. Electron microscopy revealed that the cytochrome b light and heavy chains were localized primarily (80%) to 0.1-0.2-micron round or elliptical granule-like structures in neutrophils and 0.4-0.5-micron granules in eosinophils. Approximately 20% of the cytochrome b was localized to the surface, confirming the subcellular fractionation studies. Double staining experiments on the neutrophils, using polyclonal rabbit anti-lactoferrin antibody, indicated that the cytochrome-bearing structures also contained lactoferrin and thus were specific granules. When the analysis was performed on neutrophils that had phagocytosed Staphylococcus aureus, cytochrome b was found in the phagosomal membrane adjoining the bacterial cell wall.

Animals↗
PubMed1990

1990 Ogura memorial lecture: moral dilemmas in head and neck cancer.

Neither morality nor dilemma can be defined meaningfully in the concept of the practical management of head and neck cancer. Although both have important implications, particularly with regard to ethnic and social factors, they play a relatively minor role in determining management policy. With little knowledge of the intrinsic causes of cancer and with a treatment strategy limited to radiotherapy and surgery, our desire for cure must be tempered by concern to avoid any increase in patient privations. My philosophy, based upon the care of more than 3500 patients over almost 30 years, reflects some of the difficulties of applying the concept "do nothing that may cause harm," while offering each patient the opportunity for long-term cure.

Disclosure↗
PubMed1989

Fructosamines in uraemia and renal replacement therapy.

Serum fructosamines and glycosylated haemoglobin have been examined in groups of patients with (n = 27) and without (n = 39) diabetes mellitus and chronic renal failure, or undergoing renal replacement therapy. Elevated values of fructosamines were found in nondiabetic haemodialysis patients as compared to the other non-diabetic patients. The relationship between fructosamines and glycosylated haemoglobin appeared to be attenuated by uraemia. Successful pancreatic transplantation returned fructosamine and glycosylated haemoglobin values to normal.

Adult↗
PubMed1989

Predictors of death from chronic graft-versus-host disease after bone marrow transplantation.

Chronic graft-v-host disease (chronic GVHD) is a frequent cause of late morbidity and death after bone marrow transplantation (BMT). The actuarial survival after onset of chronic GVHD in 85 patients was 42% (95%Cl = 29%, 54%) at 10 years. Baseline characteristics present at the onset of chronic GVHD (before therapy) in 85 patients were reviewed to determine which were risk factors for death. In a multivariate proportional hazards analysis, three baseline factors emerged as independent predictors of death: progressive presentation (chronic GVHD following acute GVHD without resolution of acute GVHD; hazard ratio of 4.1, 95% Cl = 2.1 to 7.8), lichenoid changes on skin histology (hazard ratio of 2.2, 95% Cl = 1.1 to 4.3), and elevation of serum bilirubin greater than 1.2 mg/dL (hazard ratio = 2.1, 95% Cl = 1.1 to 4.1). Actuarial survival of 23 chronic GVHD patients with none of these risk factors was 70% at 6 years (95% Cl = 38%, 88%). Thirty-eight patients with one of these risk factors had a projected 6-year survival of 43% (95% Cl = 21%, 63%). The 29 patients with any combination of two or more of these factors had a projected 6-year survival of only 20% (95% Cl = 8%, 37%). Identification of baseline risk factors should facilitate design of trials of chronic GVHD therapies and assignment of high-risk patients to more aggressive innovative therapeutic regimens.

Actuarial Analysis↗
PubMed1988

The use of intravenous pancuronium bromide to produce fetal paralysis during intravascular transfusion.

Intravascular fetal transfusion can be complicated by difficulty in maintaining vascular access because of fetal movements. Treatment by intramuscular pancuronium bromide has been proposed as a means of arresting fetal movements, although this treatment requires a separate puncture for injection. We report in this article our experience with intravenous fetal injection of pancuronium bromide to produce muscular paralysis during fetal transfusion.

Blood Transfusion, Intrauterine↗
PubMed1988

Hypofractionation reduces the therapeutic ratio in early glottic carcinoma.

From 1969-1985 two types of fractionation schedules with similar time, dose, and fractionation factor (TDF) values were used to treat 197 patients with Tis, T1, and T2 squamous cell carcinoma of the vocal cord. One hundred and thirty-one patients were treated with conventional daily 2.0 Gy fractions, and 66 patients were treated once per week with large (5.5-6.6 Gy) fractions (hypofractionated group); both groups were treated over a period of approximately 6 weeks. The local failure and complication rates for patients completing treatment in the two groups were compared; a patient was regarded as having suffered a serious complication of treatment if laryngectomy or tracheostomy had to be performed in the absence of active disease, or if antibiotics and/or corticosteroids had to be prescribed for laryngeal oedema and/or necrosis. In patients with Tis and T1 disease, the failure rate was worse in the hypofractionated group than in the conventionally treated group (p = 0.06). In the smaller group of T2 patients, no significant difference was found in the failure rates between the hypo- and conventionally fractionated groups. Complication rates were similar in Tis/T1 and T2 patients, but significantly higher in the hypofractionated group (p less than 0.001). Neither stage nor fractionation schedule had an effect on survival, but laryngectomy/tracheostomy free survival was significantly worse in Tis/T1 patients receiving hypofractionated treatment, (p = 0.008) although not in T2 patients. These results indicate that in Tis/T1 glottic cancer, hypofractionation of radiotherapy produces a reduction in the therapeutic ratio.

Adult↗
PubMed1987

Renal brush border glutamine transport: comparison between in situ and isolate membrane vesicle uptake.

Glutamine uptake by renal cortical brush-border vesicles was compared to transport expressed by the functioning isolated kidney. Comparisons were made with regard to sodium dependency and the adaptive increase induced by chronic metabolic acidosis in the rat. The results show an absolute dependency upon a sodium gradient; sodium-independent glutamine uptake has no counterpart in situ. In addition, acidosis-induced adaptive increase in vesicle glutamine uptake has no counterpart in situ. Rather, the apparent adaptation reflects extravesicular gamma-glutamyltransferase-mediated conversion to glutamate and subsequent accumulation; acidosis-induced adaptation of this enzyme largely explains the apparent adaptation in glutamine uptake. Consequently the role of membrane transport in glutamine flux regulation can be assessed providing metabolic conversion is controlled.

Acidosis↗
PubMed1987

Effect of precisely identified mutations in the spoIIAC gene of Bacillus subtilis on the toxicity of the sigma-like gene product to Escherichia coli.

Yudkin (1986) has shown that the spoIIAC gene of Bacillus subtilis cannot be cloned in Escherichia coli in such an orientation that it is expressed. This toxicity of the gene product has been attributed to its close homology with the sigma subunit of the E. coli RNA polymerase. The effect of six individual mutations in spoIIAC has now been studied. All six mutant genes could be cloned in E. coli in an orientation that does not allow expression. When in the orientation that permits expression, one mutant gene could not be cloned, and a second substantially hampered growth; both mutations lie in the region that is believed to encode the DNA-binding domain of the protein. By contrast, two missense mutations in the region of the gene thought to encode the domain that binds to the core RNA polymerase rendered the protein harmless in E. coli, as did two nonsense mutations.

Bacillus subtilis↗
PubMed1987

Hematopoietic effects of continuous intravenous infusion of mice with growth factors produced by the WEHI-3 cell line.

A method for continuous intravenous infusion of unanesthetized adult C3H/HeJ or Wx/Wv anemic mice was designed using cage immobilization and a tail vein catheter connected to a model 940 Harvard infusion pump. Infusates included: WEHI-3 cell line dialyzed, 5 times concentrated conditioned medium containing multi-colony-stimulating factor (C-SF) interleukin 3 (IL-3); purified murine IL-3; bacterial endotoxin; serum-free medium, or normal saline. Mice were monitored at days 5-7 after infusion for complete peripheral blood counts and production of granulocytes in vitro by explanted marrow in long-term bone marrow cultures. We observed a stimulatory effect of WEHI-3 conditioned medium infusion that was not attributable to endotoxin and produced significant increases in peripheral blood WBC count and neutrophils, colony-forming units in spleen and numbers of granulocyte/macrophage colony-forming unit culture responsive to both C-SF-1 (L cell C-SF) and multi-C-SF in vitro. This infusion method should prove valuable for test of the in vivo effects of purified growth factors and molecularly cloned hematopoietins.

Animals↗
PubMed1987

Once-daily sustained-release theophylline reduces diurnal variation in spirometry and symptomatology in adult asthmatics.

In 22 adult asthmatics (mean age, 55.2 +/- 15.4 yr), we compared Uniphyl given once a day to Theo-Dur given twice a day using a randomized, double-blind, two-phase crossover trial. All patients demonstrated acute bronchodilator responsiveness (FEV1 increase greater than 15%) to inhaled salbutamol and were dependent upon both orally administered theophylline and inhaled salbutamol at time of entry. Each phase lasted 9 days, the first 2 days of which were a theophylline washout. Uniphyl was given once a day at 8 P.M. and Theo-Dur was given twice a day at 8 A.M. and at 8 P.M. For each patient, the total daily theophylline dose was the same during both phases. Asthma symptoms, drug side effects, and PEFR were recorded at 8 A.M. and at 4 and 8 P.M. each day. On Days 7, 8, and 9 of each phase, serum theophylline concentrations were measured and spirometry was performed at 8 A.M. and at 4 and 8 P.M. The results demonstrated significant differences in both pharmacokinetic and clinical efficacy between the 2 drugs. Uniphyl produced greater "peak" and lower "trough" theophylline concentrations than did Theo-Dur, although both lower "trough" theophylline concentrations than did Theo-Dur, although both drugs maintained concentrations within the accepted therapeutic range. In contrast to the pharmacokinetic findings, Uniphyl was associated with significantly less fluctuation in pulmonary function throughout the day, and the values at 8 A.M. for FEV1, PEFR, and wheeze demonstrated significant clinical efficacy in favor of Uniphyl.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Biological characterization of cloned permanent stromal cell lines from anemic Sl/Sld mice and +/+ littermates.

Permanent cloned bone marrow stromal cell lines, designated Sld1, Sld2, Sld3, were derived from long-term bone marrow cultures (LTBMC) of Sl/Sld mice and littermate WCB6F1 mice (designated +/+1, +/+2, +/+1.10, and +/+2.4). Production of extracellular matrix proteins by these cell lines was detected using specific antibodies. Fibronectin, laminin, and collagen type IV were detected in all clonal cell lines tested. Each cloned stromal cell line or parent stromal cell culture was also tested in vitro for support of engrafted hemopoietic stem cells. Engrafted hemopoietic stem cells from C57BL/6J LTBMCs forming CFU-GEMM and BFUe colonies were supported at 76% and 44% efficiency by lines +/+2.4 and +/+1.10, respectively, compared to the number recovered from parent uncloned C57BL/6J stromal cell cultures. In contrast, cell lines Sld1 and Sld3 were significantly less supportive of CFU-GEMM progenitor cells (14% and 18% efficiency, respectively) and erythroid progenitors (6% and less than 0.1% efficiency, respectively). Some Sld lines also showed reduced support compared to +/+ cell lines of a clonal multipotential erythroid cell line B6SUtA. These permanent stromal cell lines should be useful in elucidation of the specific microenvironmental factors required for support of multilineage and erythroid progenitor cells.

Anemia, Macrocytic↗
PubMed1986

Relation between electrocardiographic and enzymatic methods of estimating acute myocardial infarct size.

The extent of initial acute myocardial infarction (AMI) and subsequent patient prognosis were studied using 2 independent indicators of AMI size. Two inexpensive, readily available techniques, the complete Selvester QRS score from the standard 12-lead electrocardiogram and the peak value of the isoenzyme MB of creatine kinase (CK-MB), were evaluated in 125 patients with initial AMI. The overall correlation between peak CK-MB and QRS score was fair (0.57), with marked difference according to anterior (0.72) or inferior (0.35) location. The prognostic capabilities of each measurement varied. Peak CK-MB provided significant information concerning hospital morbidity or early mortality (within 30 days) for both anterior (chi 2 = 9.83) and inferior (chi 2 = 7.68) AMI locations; however, the QRS score was significant only for anterior AMI (chi 2 = 9.50). For total 24-month mortality, the QRS score alone provided the most information (chi 2 = 10.0, p = 0.0016), which was not improved with the addition of CK-MB (chi 2 = 0.07, p = 0.79). This study shows a good relation between these 2 independent estimates of AMI size for patients with anterior AMI location. Both QRS and CK-MB results are significantly related to early morbidity and mortality; however, only the QRS score is related to total 24-month prognosis.

Aged↗