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Biomedical subjects

R Norris

Publications and source records attributed to R Norris.

At least 37 records · Page 2Linked to original sources

Comparison of effects of thrombolytic therapy on left ventricular function in patients over with those under 60 years of age.

This study examined the effect of age on left ventricular (LV) function, assessed by contrast ventriculography 3 weeks after a first acute myocardial infarction in 312 patients who received thrombolytic therapy within 4 hours of the onset of infarction and in 83 patients who received placebo. Streptokinase was given to 188 patients and recombinant tissue-type plasminogen activator (rt-PA) to 124. Patients were divided into 2 age groups: less than 60 years (n = 244) and greater than or equal to 60 years (n = 151). Thrombolytic therapy improved ejection fraction in both age groups: from 54 +/- 13 to 59 +/- 11% (p = 0.021) in the younger group and from 50 +/- 14 to 57 +/- 13% (p = 0.004) in the older group. Ejection fraction was identical in streptokinase- and rt-PA-treated patients. Multifactor analysis of variance revealed that younger age and thrombolytic therapy were independently associated with improved ejection fraction. Thrombolytic therapy also reduced end-systolic volume (p = 0.001) by 14 ml in the elderly and 9 ml in the younger group. Minor bleeding complications were more frequent in the elderly and 3 serious hemorrhages occurred in patients greater than or equal to 60 years. These findings reveal that thrombolysis improves LV function in all age groups studied. Because increasing age is independently associated with a lower ejection fraction after acute myocardial infarction, thrombolytic therapy may confer greater benefits in older patients.

Age Factors↗

The effects of aerobic and anaerobic training on fitness, blood pressure, and psychological stress and well-being.

To determine whether fitness alters psychological and physiological indices of well-being, male police officers were assigned to either an aerobic or anaerobic training condition or to a no treatment control group. The training groups met three times per week in 45 min sessions aimed at improving either cardiovascular endurance or muscle strength. Aerobic fitness level, heart rate, blood pressure and self-report of stress and well-being were measured prior to and following 10 weeks of training. Post-training fitness measures confirmed the effectiveness of training and between group differences for physiological and self-report measures were found. Subjects undergoing aerobic training evinced larger changes on the self-report measures of well-being and stress than the anaerobic trainers and both groups showed significant improvement when compared to controls. This experiment provides support for the hypothesis that exercise, and in particular aerobic exercise, has positive effects of well-being. It is suggested that future research might usefully explore the particular contribution of different aspects of the training situation to these effects.

Adaptation, Psychological↗

Human breast epithelial xenografts: an immunocytochemical and ultrastructural study of differentiation and lactogenic response.

Fragments of ductal and lobular epithelium ('organoids') produced by collagenase digestion of reduction-mammoplasty specimens were injected into athymic 'nude' mice. These heterospecific tissues were accepted without rejection, and the presence of xenografts was confirmed by cytology, immunocytochemistry and chromatin staining. Lactation, as confirmed by immunocytochemical and ultrastructural criteria, was observed in the grafted human epithelium during murine pregnancy at both intra- and extra-mammary sites.

Actins↗

Serum fructosamine as a screening method for diabetes mellitus in patients with suspected acute myocardial infarction.

It is important to identify diabetic patients in a coronary care population because they have a higher risk of suffering congestive heart failure, dysrhythmias and death following myocardial infarction. In order to determine the most efficient screening method for diabetes, we compared fructosamine and glucose measurements on admission blood specimens from 256 consecutive patients. Of 15 (5.9%) known diabetic patients, 12 had glucose results greater than or equal to 7.8 mmol/l and nine had fructosamine levels greater than 2.87 mmol/l. However, elevated glucose results were also found in a high proportion (49.2%) of patients with no previous history of diabetes. We performed glucose tolerance tests in 107 patients after discharge to determine the frequency of false-positive observations. Fructosamine yielded five (4.6%) false-positive results, whereas plasma glucose yielded 47 (43.9%) false-positive observations. We conclude that serum fructosamine provides a more specific screening method for diabetes in this population because the results are unaffected by stress hyperglycemia.

Adult↗

Irradiation with misonidazole and hyperbaric oxygen: final report on a randomized trial in advanced head and neck cancer.

One hundred and thirty patients with locally advanced squamous carcinoma of the head and neck were treated in a prospective randomized trial to compare conventional irradiation (63.00 Gy in 30 fractions) with a combination sensitizer regimen of misonidazole and hyperbaric oxygen. The drug (2.0 gm/m2) was given with each of six fractions of 6.0 Gy in hyperbaric oxygen at 3 ATA. The results support a previous study and favor the combination at 1 year at better than the 10% level. This regimen could be useful for bulky primary or nodal disease.

Carcinoma, Squamous Cell↗

Delayed paraplegia complicating sublaminar segmental spinal instrumentation.

The cases of two patients with delayed paraplegia after segmental spinal instrumentation with sublaminar wiring are reported. Both patients had complex spinal deformities and had transient neural deficits after the first-stage procedure of anterior release and spine fusion. They had uneventful spinal-cord monitoring during the second-stage procedure of posterior instrumentation and fusion, and function of the lower extremities was present immediately after that operation. Paraplegia then ensued, and was recognized thirty hours later in one patient and six days later in the other. Considering our reproducible and reliable experience (no false-negative results) with spinal cord monitoring in 307 operations, we propose that the delayed onset of paraplegia resulted from a progression of ischemic and edema-producing events that had not developed sufficiently intraoperatively to be reflected by the monitoring. The paraplegia became evident only when the subarachnoid space was obstructed because of progressive postoperative neural edema. The presence of sublaminar implants in narrow, kyphotic segments of the spinal canal probably exacerbated the neural irritation by dural impingement, which was seen myelographically.

Adolescent↗

The pharmacokinetics of fentiazac and its metabolite, p-hydroxyfentiazac, after twice-daily oral administration to male volunteers.

The pharmacokinetics of the anti-inflammatory agent fentiazac and its principal plasma metabolite, p-hydroxyfentiazac, have been investigated after repeated oral administration of fentiazac to male volunteers. Each volunteer received 200 mg of fentiazac twice daily for 15 d. Absorption was quite rapid, though some inter-subject variation in rates of absorption and bioavailability was observed. tmax values after the first dose ranged from 0.75-3 h while Cpmax values were 1050-4880 ng/ml. Elimination of fentiazac from plasma occurred rapidly in curvilinear fashion, so that concentrations were only 1% of their maximum value by 12 h after dosing. Maximum concentrations of p-hydroxyfentiazac after a single dose of fentiazac were 25.6-79.4% of those of fentiazac and were achieved at similar times. The metabolite was more slowly eliminated; the mean concentration of p-hydroxyfentiazac 12 h after a single dose was still 8% of its maximal value. On repeated administration, AUC0-12 h values for fentiazac and hydroxyfentiazac increased, as indicated by accumulation factors of 1.17 +/- 0.11 and 1.30 +/- 0.11 on days 8 and 15, respectively, for fentiazac and 1.72 +/- 0.15 and 1.77 +/- 0.10 for hydroxyfentiazac. There was no significant difference between days 8 and 15 in the extent of accumulation of either compound. Trough concentrations of fentiazac and hydroxyfentiazac on days 12 and 15 were similar to those on day 8. The clinical significance of these observations is discussed.

Acetates↗

Preliminary studies on the fate of 14C-fentiazac in man.

The disposition of the anti-inflammatory drug fentiazac has been investigated in male volunteers after oral administration of single 200 mg doses of the 14C-labelled compound. Excretion took place predominantly via the faeces with approx. 67% of the dose being recovered in the 0-5 d collection. Urinary excretion accounted for a further 18%, most of which was excreted in the first 24 h. Examination of urinary extracts before and after treatment with beta-glucuronidase showed a relatively simple pattern of metabolites, the major excretion product being a conjugate of p-hydroxyfentiazac. No conjugated material was found in faeces. The major components were p-hydroxyfentiazac and fentiazac itself, in a ratio of 3:2; a minor metabolite was also present, accounting for 10% of the faecal radioactivity.

Acetates↗

Immunoglobulin as the major low density lipoprotein binding protein in plasma.

Plasma from normal humans and Chinese hamsters was shown to contain material which binds to low density lipoproteins (LDL). The binding capacity of these plasmas was demonstrated by passive hemagglutination against human LDL-coated red blood cells. The plasmas were fractionated by affinity chromatography, gel filtration and electrophoresis. Immunologic analyses of these fractions showed that IgM and IgA were the major plasma proteins responsible for the LDL binding titers of human and hamster plasmas. The titer of binding protein in diabetic and non-diabetic humans and hamsters was also determined.

Animals↗

Evidence for association-activation effects in reactions of papain from studies on its reactivity towards isomeric two-protonic-state reactivity probes.

4-(N-Aminoethyl 4-pyridyl disulphide)-7-nitrobenzo-2-oxa-1,3-diazole was synthesized and evaluted as a two-protonic-state reactivity probe by kinetic study of its reactions with papain (EC 3.4.22.2) and with benzimidazol-2-ylmethanethiol. Evidence is presented to suggest that: (i) both this probe molecule and its 2-pyridyl isomer bind to papain; (ii) the binding is followed by a change in the environment of the thiol group of cysteine-25; (iii) the striking rate maximum in neutral media observed in the reaction of papain with the 2-pyridyl isomer but not with the 4-pyridyl isomer arises from association of the 2-pyridyl leaving group with the imidazolium ion of histidine-159.

Binding Sites↗

Patient expectation: what is comprehensive health care?

A patient expectation survey was developed and implemented in order to define the spectrum of health care activities expected from the University of Nebraska Family Health Centers. The hypothesis underlying the survey is that patient expectations or opinions vary considerably among the members of any given population. High expectation is present for office visits, emergency services, yearly physical examination, and performance of chest x-ray, blood test, proctoscopy, and eye examination. Psychiatric services, marital counseling, youth counseling, nursing home care, and health education are indicated as not necessary by a plurality of the respondents. Examination of the responses by age, sex, and payment status through canonical correlation reveals a number of strong correlations of specific subgroups and expectations. Factor analysis revealed three independent factors or clusters representating health care issues as perceived by the patient. This study and further similar studies will be helpful in aiding the family physician's understanding of what patients expect. Through a better understanding of patient expectation, patient satisfaction and compliance may be improved.

Adolescent↗

A convenient method of preparation of high-activity urease from Canavalia ensiformis by covalent chromatography and an investigation of its thiol groups with 2,2'-dipyridyl disulphide as a thiol titrant and reactivity probe.

1. A convenient method of preparation of jack-bean urease (EC3.5.1.5) involving covalent chromatography by thiol-disulphide interchange is described. 2. Urease thus prepared has specific activity comparable with the highest value yet reported (44.5 +/- 1.47 kat/kg, Km = 3.32 +/- 0.05 mM; kcat. = 2.15 X 10(4) +/- 0.05 X 10(4)s-1 at pH7.0 and 38 degrees C). 3. Titration of the urease thiol groups with 2,2'-dipyridyl disulphide (2-Py-S-S-2-Py) and application of the method of Tsou Chen-Lu [(1962) Sci. Sin. 11, 1535-1558] suggests that the urease molecule (assumed to have mol.wt. 483000 and epsilon280 = 2.84 X 10(5) litre-mol-1-cm-1) contains 24 inessential thiol groups of relatively high reactivity (class-I), six 'essential' thiol groups of low reactivity (class-II) and 54 buried thiol groups (class-III) which are exposed in 6M-guanidinium chloride. 4. The reaction of the class-I thiol groups with 2-Py-S-S-2-Py was studied in the pH range 6-11 at 25 degrees C(I = 0.1 mol/l) by stopped-flow spectrophotometry, and the analogous reaction of the class-II thiol groups by conventional spectrophotometry. 5. The class-I thiol groups consist of at least two sub-classes whose reactions with 2-Py-S-S-2-Py are characterized by (a) pKa = 9.1, k = 1.56 X 10(4)M-1-s-1 and (b) pKa = 8.1, k = 8.05 X 10(2)M-1-s-1 respectively. The reaction of the class-II thiol groups is characterized by pKa = 9.15 and k = 1.60 X 10(2)M-1-s-1. 6. At pH values 7-8 the class-I thiol groups consist of approx. 50% class-Ia groups and 50% class-Ib groups. The ratio class Ia/class Ib decreases an or equal to approx. 9.5, and at high pH the class-I thiol groups consist of at most 25% class-Ia groups and at least 75% class-Ib groups. 7. The reactivity of the class-II thiol groups towards 2-Py-S-S-2-Py is insensitive to the nature of the group used to block the class-I thiols. 8. All the 'essential' thiol groups in urease appear to be eeactive only as uncomplicated thiolate ions. The implications of this for the active-centre chemistry of urease relative to that of the thiol proteinases are discussed.

2,2'-Dipyridyl↗

A reporter group delivery system with both absolute and selective specificity for thiol groups and an improved fluorescent probe containing the 7-nitrobenzo-2-oxa-1,3-diazole moiety.

1. 4-(N-2-Aminoethyl2'-pyridyl disulphide)-7-nitrobenzo-2-oxa-1,3-diazole (compound I) was synthesized and evaluated as a fluorescent labelling reagent for thiol groups. 2. The design of compound (I) as one example of a general type of reporter group delivery reagent (2-pyridyl-S-S-X, where X contains an environmentally sensitive spectroscopic probe) is discussed. 3. The electronic absorption spectrum of compound (I) was determined over a wide range of pH and the spectral changes that accompany its reaction with low-molecular-weight thiols, e.g. L-cysteine, and with papain (EC 3.4.22.2) and bovine serum albumin are discussed. 4. A new value of epsilon343 for 2-thiopyridone (Py-2-SH) was determined as 8.08 X 10(3) +/- 0.08 X 10(3)M-1-cm-1. 5. Spectral analysis of the reactions of compound (I) with L-cysteine and with papain (in the pH range 3.5-8.0) showed that even under equimolar conditions the reaction (thiol-disulphide interchange to release Py-2-SH) is essentially stoicheimoetric and probably proceeds by specific attack at the sulphur atom distal from the pyridyl ring of compound (I). 6. The fluorescence-emission spectra of compound (I) and of the products of its reaction with papain and with ficin (EC 3.4.22.3) were determined. Compound (I) is highly fluorescent in aqueous solution. Excitation within the intense visible absorption band (lambda max. 481 nm, epsilon max. 2.52 X 10(4)M-1-cm-1) provides green fluorescence with an emission maximum at 540 nm. Both papain and ficin labelled by reaction with compound (I) are characterized by fluorescence-emission maxima (535 nm and 530 nm respectively) of even higher intensity. The fluorescence emission of the product of the reaction of papain with compound (I) was shown to be 25 times more intense than that of the product of the reaction of papain with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (Nbd chloride). 7. The second-order rate constants (k2) for the reactions of compound (I) and of Nbd chloride with GSH, papain, albumin, ficin, 2-benzimidazolylmethanethiol and 2-benzimidazolylethanethiol were determined at 25.0 degrees C and various pH values. At pH4 the values of k2(compound I)/k2(Nbd chloride) are: GSH, 288; albumin, 36; papain 3 X 10(3); ficin, 3 X 10(4). 8. The pH-k2 profiles for the reactions of compound (I) and of Nbd chloride with the two 2-benzimidazolylalkanethiols were determined. Of the four profiles only that for the reaction of compound (I) with 2-benzimidazolylmethanethiol is characterized by a striking rate maximum in acidic media.

Benzimidazoles↗