External rhinoplasty: intact columellar approach.
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Humans↗
Biomedical subjects
S Freeman
Publications and source records attributed to S Freeman.
ABR threshold is a function of blood oxygen level.
In order to determine if there is a relation between auditory threshold and oxygen availability, cats were anesthetized, paralyzed and ventilated with room air and with hypoxic gas mixtures. Auditory nerve-brain stem evoked response (ABR) thresholds and arterial blood oxygen levels [partial pressures (PaO2) and percent saturation (SaO2)] were determined. The ABR threshold was unchanged as long as PaO2 was above 30 mm Hg (SaO2 greater than 45%). Below PaO2 20 mmHg (SaO2 less than 25%) the animal was not viable. Between these values, the hypoxia caused ABR threshold elevations which were reversible when the animal was again respirated with room air. ABR threshold was an inverse function of blood O2 level with an approximate 3.05 dB elevation for every mmHg decrease in PaO2 (2.89 dB/% SaO2). These findings are probably due to hypoxia induced depression of the endocochlear potential. Since ABR could be recorded in premature human neonates after at least 28 weeks gestation and since the human fetus in utero is also hypoxic, these results indicate that the fetus (greater than 28 weeks gestational age) has a sensorineural hearing loss in addition to a conductive loss.
Animals↗
Controlled clinical trial of adjuvant immunotherapy with BCG and neuraminidase-treated autologous tumour cells in large bowel cancer.
A controlled, randomised clinical trial of immunotherapy was performed in 301 patients with stage B or C colorectal cancer. The immunotherapy treatment consisted of 18 vaccinations over a 2 year period following surgery with a combination of BCG given by scarification plus subcutaneous injection of Vibrio cholera neuraminidase (VCN)-modified autologous tumour cells. Five year follow-up has now been completed in all patients. The immunotherapy did not alter either the disease-free interval or the overall survival of patients in comparison with a control group of patients not receiving immunotherapy.
Adenocarcinoma↗
Influence of infusion time on unchanged cisplatin disposition in patients with ovarian cancer.
The disposition of unchanged cisplatin in ten patients with ovarian cancer receiving 2-h infusions of 100 mg/m2 was compared with that of ten patients receiving 6-h infusions. A high-performance liquid chromatographic assay specific for the unchanged drug was used and all collected samples were rapidly processed. Patients were catheterized for urine collections. Cisplatin renal clearance was significantly lower after 6-hour infusions (52.8 +/- 16.2 ml/min per m2) than after 2-h infusions (87.1 +/- 38.2 ml/min per m2) (P = 0.026). Total clearance was also lower and less variable, although not significantly, in patients receiving the longer infusion. No differences in nonrenal clearance, volume of distribution, or half-life were observed between the two groups. There was only a poor relationship between cisplatin renal clearance and creatinine clearance after 2-h (r2 = 0.02; P = 0.66) and 6-h infusions (r2 = 0.18; P = 0.23). A single cisplatin plasma level obtained at the end of the infusion proved to be a good predictor of total cisplatin clearance after both 2-h (r2 = 0.70; P = 0.0096) and 6-h infusions (r2 = 0.97; P = 0.0001). This level was not significantly related to the relatively small changes in creatinine clearance that occurred after three courses of treatment.
Aged↗
EEG mean frequencies are sensitive indices of phenylalanine effects on normal brain.
We previously reported that changes in plasma phenylalanine (PHE) concentrations of 1000 microM or more adversely affected cognitive function and reduced mean frequency of the EEG power spectrum. In the present study, we characterized EEG effects of changes in plasma PHE from physiological to supraphysiological concentrations. Subjects were mentally normal children and adult volunteers with 3 different genotypes for phenylalanine hydroxylase (PHY): homozygous deficient, heterozygous, and homozygous normal. Double-blinded crossover studies were performed at equilibrium during PHE restriction and supplementation. The mean frequency of the power spectrum and the mean across a set of alpha-theta factors showed highly significant, reversible, generalized EEG slowing during PHE supplementation in subjects homozygous for PHY deficiency. Smaller but significant changes in EEG mean frequencies occurred in the heterozygous and normal subjects. Spectral profiles of EEG change were similar in both groups; the mean alpha-theta was more sensitive in the second group. Demonstration of EEG changes with PHE supplementation in normal individuals has important dietary implications.
Adult↗
Tendency to irritation: sensitive skin.
The plausibility of the concept of "sensitive skin" evokes discussion and often amusement, because of the variance of the number of opinions compared with the amount of data, at least until recently. This report presents recent biologically oriented data that suggest that sensitive skin is a reality and is assessable with the use of contemporary methods.
Body Water↗
Phaeohyphomycosis due to Phialophora richardsiae.
Phaeohyphomycosis, an infection characterised by dematiaceous yeast-like cells, hyphae and pseudohyphae in tissue, is an uncommon condition, often affecting immunosuppressed patients. A sixty four year old boat-builder, receiving treatment with prednisone and azathioprine developed multiple cutaneous nodules on the extremities. Histology showed a mixed dermal inflammatory infiltrate with scattered spores and hyphae. Culture revealed two organisms, Phialophora richardsiae and Exophiala jeanselmei. Fluorocytosine was initially given but the organism was found to be resistant. Since side effects have been associated with long term ketoconazole therapy, a less toxic and more potent triazole compound, itraconazole, was used. After three months, the lesions had completely resolved without adverse clinical or biochemical changes.
Antifungal Agents↗
Two- versus 24-hour infusion of cisplatin: pharmacokinetic considerations.
The disposition of unchanged cisplatin was compared after two- and 24-hour intravenous (IV) infusion to eight patients with germ cell cancer (dose, 100 mg/m2), 14 patients with head and neck cancer (dose, seven patients 50 mg/m2; seven patients, 100 mg/m2). Patients were randomized to receive either a two- or 24-hour infusion in the first course of treatment and the reverse in the second course. Cisplatin renal clearance, total clearance, and the percentage of the dose excreted unchanged in urine were significantly lower with the longer infusion. Total clearance was 345 +/- 97.0 mL/min/m2 after the two-hour infusion and 268 +/- 70.7 mL/min/m2 after the 24-hour infusion (P less than .0001). Renal clearance was 79.1 +/- 35.3 mL/min/m2 and 34.1 +/- 14.9 mL/min/m2 (P less than .0001). The percentage of the dose excreted unchanged in urine was 22.9 +/- 6.5% and 12.8 +/- 4.0%, respectively (P less than .0001). The ratio of cisplatin renal clearance to creatinine clearance was 1.95 +/- .96 after the two-hour infusion and .90 +/- .40 after the 24-hour infusion (P less than .001). There was only a poor relationship between cisplatin renal clearance and creatinine clearance after a two-hour infusion (r2 = .05, P greater than .1) or 24-hour infusion (r2 = .18, P greater than .05). The severity of emesis was graded on a four-point scale and was significantly less with the 24-hour infusion than with the two-hour infusion (P less than .05). Twenty-four-hour infusion of cisplatin resulted in greater drug retention in patients due to reduced renal clearance, but was also associated with reduced emetic toxicity, probably as a result of lower peak plasma levels.
Adolescent↗
The stereochemical course of phospho group transfer catalyzed by rat liver 6-phosphofructo-2-kinase.
Adenosine [gamma-(S)-16O,17O,18O]triphosphate was used as substrate in the phosphokinase reaction catalyzed by 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase. The product D-fructose 2,6-[2-16O,17O,18O]bisphosphate was then used as substrate in the alkaline phosphatase-mediated transfer of the phospho groups to (S)-butane-1,3-diol, where the configuration at phosphorus has been determined. Although there was approximately equal transfer by alkaline phosphatase of the labeled 2- and the unlabeled 6-phospho groups, the subsequent assignment of configuration of the chiral phospho group from the 2-position was unambiguous. It was found that 6-phosphofructo-2-kinase proceeds by a pathway that results in net inversion of the configuration at phosphorus. The simplest interpretation of this result is that the phospho group is transferred directly between substrates in a ternary complex by an "in-line" mechanism not involving a phosphoenzyme intermediate. This conclusion is consistent with the fact that the enzyme cannot be labeled by [gamma-32P]ATP and with steady-state kinetic data that suggest an ordered sequential mechanism. This finding also indicates that the adenine nucleotide and sugar phosphate isotope exchange reactions catalyzed by the enzyme are not relevant to the normal catalytic pathway of the kinase.
Adenosine Triphosphate↗
Phosphonate biosynthesis: isolation of the enzyme responsible for the formation of a carbon-phosphorus bond.
The first isolation of a naturally occurring phosphonate in 1959 led rapidly to the discovery of a variety of metabolites containing a phosphorus-carbon bond. Phosphonates have been found in bacteria, fungi, and higher organisms such as the snail schistosome vector Biomphalaria. The biosynthetic path to the P-C bond has, however, remained undefined. Thus although it was shown twenty years ago that the isotope label from [14C]glucose or from [32P]phosphoenolpyruvate is incorporated into 2-aminoethylphosphonate by the protozoan Tetrahymena pyriformis, the presumed stoichiometric transformation of phosphoenolpyruvate to phosphonopyruvate has never been demonstrated. Low conversions of phosphoenolpyruvate into 2-aminoethylphosphonate and the trapping of phosphonopyruvate from phosphoenolpyruvate have been reported, but these reactions have not proved reproducible, and the existence of the critical enzyme, phosphoenolpyruvate phosphonomutase, has remained notional. We now report experiments that resolve this enigma, and describe the isolation and characterization of the pure mutase from T. pyriformis.
Amino Acid Sequence↗
Stereochemistry of phospho group transfer catalyzed by a mutant alkaline phosphatase.
The stereochemical course of the phospho group transfer catalyzed by mutant (S102C) alkaline phosphatase from Escherichia coli was investigated by using 31P nuclear magnetic resonance spectroscopy. Transphosphorylation from 4-nitrophenyl (Rp)-[16O, 17O, 18O]phosphate to (S)-propane-1,2-diol occurs with overall retention of configuration at phosphorus. This result is consistent with the view that the hydrolysis of substrates by this mutant enzyme proceeds by way of a covalent phosphoenzyme intermediate in the same manner as the wild-type alkaline phosphatase.
Alkaline Phosphatase↗
Concomitant changes in the acoustic impedance and the cochlear microphonic potentials during twitch contractions of the middle ear muscles in cats.
The effect of twitch contractions of the middle ear muscles in cats on sound transmission through the middle ear (as measured by the cochlear microphonic potential of the inner ear) was compared with the simultaneous changes in the acoustic input impedance of the middle ear at the same frequency. It was found that decreases in impedance were related to an increase in the amplitude of the cochlear microphonics and vice versa. This may imply that decreases in impedance measured during the initial phase of the acoustic reflex in man are true decreases and are not due to transient decoupling of the ossicular chain at any point.
Acoustic Impedance Tests↗
Perinatal hypoxia and auditory brainstem response thresholds: no evidence of permanent hearing loss.
It has been suggested that pre-natal and or peri-natal hypoxia can cause permanent hearing loss as a result of interference with the generation of the endocochlear potential, especially if this interference occurs during the critical period of endocochlear potential development. This hypothesis was tested in 4 series of experiments: in neonatal rats exposed to pure nitrogen for several minutes; in neonatal and adult cats respirated with hypoxic gas mixture for an hour; in neonatal rats and cats breathing hypoxic gas mixture for several hours; and in neonatal rats in hypobaric chamber for several days. In each experiment, the auditory nerve-brainstem evoked response threshold was elevated during hypoxia in those animals in which it could be measured but was normal when determined several hours to days later. This is evidence for a remarkable ability of the auditory system to recover from periods of hypoxia even during the critical period of endocochlear potential development.
Animals↗
Study of irritant contact dermatitis produced by repeat patch test with sodium lauryl sulfate and assessed by visual methods, transepidermal water loss, and laser Doppler velocimetry.
Eleven subjects received patch tests with 2% sodium lauryl sulfate on a total of 34 anatomic sites. The irritant effect was monitored by visual means, laser Doppler velocimetry, and measurement of transepidermal water loss. After 1 week, repeat patch tests with 2% sodium lauryl sulfate were performed on the same site, and the effect was monitored as before. Although the skin had returned to normal or near normal before the repeat patch test, an augmented response to irritation was generally seen after the repeat patch test, particularly in transepidermal water loss, which showed an augmented response in 29 of the 34 anatomic sites. The clinical implications regarding the healing of contact irritant dermatitis are discussed.
Adolescent↗
Experimental closed head injury in rats: mechanical, pathophysiologic, and neurologic properties.
A model of closed head injury in rats was developed using a calibrated weight-drop device. The development of edema was studied in various brain regions (cerebral hemispheres, brain stem, cerebellum) using a linear specific gravity gradient column. Regional brain tissue density was measured within 1 min, at 15 and 60 min, 18 h, 4 and 10 days after injury to the left cerebral hemisphere, and was compared with values in sham-operated and control rats. Significant edema (i.e., reduced specific gravity) occurred only in the traumatized hemisphere and was maximal at 18 h. A neurologic severity score (NSS) was developed to evaluate the status of the rat after injury. Specific gravity was significantly correlated with NSS at 18 h after injury. The affected hemisphere displayed hemorrhagic lesions as early as one hour post head trauma (HT), which evolved into hemorrhagic necrosis at 18 h. A pathologic score, evaluated 18 h post HT based on size and severity of the lesion, was correlated with the NSS and evaluated for each rat at one hour and 18 h postimpact. This correlation was found to be highly significant. This model of brain injury may be useful in future studies on the effects of therapeutic agents.
Animals↗
Spectacle frame dermatitis due to paraphenylenediamine.
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Dermatitis, Contact↗
Allergic contact dermatitis to Noogoora Burr and Bathurst Burr.
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Adult↗
Melbourne trial of adjuvant immunotherapy in operable large bowel cancer.
A controlled randomized clinical trial was undertaken to assess the ability of combined non-specific and specific immunotherapy to alter the disease-free interval and overall survival of patients with Stage B or C large bowel cancer. The immunotherapy consisted of a 2 year programme of vaccinations with BCG and neuraminidase-treated autologous tumour cells. Three hundred and one patients entered the trial. At 5 years of follow-up there is no evidence that this form of immunotherapy can alter either the disease-free interval or survival in this group of patients.
Antigens, Neoplasm↗