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Biomedical subjects

L Miller

Publications and source records attributed to L Miller.

At least 379 records · Page 21Linked to original sources

The Potter sequence: a clinical analysis of 80 cases.

Eighty cases of Potter sequence due to a renal or urologic abnormality were studied retrospectively. The abnormal renal findings were bilateral renal agenesis in 21.25%; cystic dysplasia in 47.5%; obstructive uropathy in 25%; and others in 5.25%. Fifteen patients had multiple congenital anomalies; of these three had aneuploidy, four had autosomal recessive syndromes, and eight were of unknown cause. Results of chromosome analysis in 41 patients and 21 sets of parents were abnormal in three patients, one of whom had a balanced translocation carrier parent; two additional patients and three parents had apparently balanced translocations. There was one recurrence within the study (the first child had bilateral renal agenesis and the second cystic dysplasia). The ultrasound prenatal diagnosis of the renal abnormality was made in eight cases between 18 and 34 weeks. Family histories were suggestive of an autosomal dominant gene disorder with incomplete penetrance in four of 45 families with nonsyndromic bilateral renal agenesis and cystic dysplasia. The evaluation of patients with the Potter sequence should include an examination for nonrenal defects, autopsy, chromosome analysis, and renal ultrasound or urologic evaluation of parents. Ultrasonographic prenatal monitoring of subsequent pregnancies in such families is strongly warranted because of a definite but unknown degree of recurrence risk.

Abnormalities, Multiple↗

Mu-receptor binding in physiological media: comparison with isolated tissue data.

Mu-receptor affinities have been determined for a number of opioid drugs using a combination of isolated tissue and receptor binding techniques. The affinities of antagonists and partial agonists were determined by their ability to antagonise responses to [D-Ala2,MePhe4,Glyol5]enkephalin (GLYOL) on the rat vas deferens preparation. There was little correlation between these results and affinities measured by displacement of [3H]-GLYOL from guinea-pig brain membranes incubated in 50mM Tris buffer. By contrast, affinities measured by displacement of [3H]-naloxone from rat brain membranes incubated in a Krebs/HEPES buffer containing a non-hydrolysable analogue of GTP, agreed very closely with the isolated tissue data.

Animals↗

Mu-receptors in the C57BL mouse vas deferens.

The C57 mouse vas deferens preparation has been shown to be insensitive to mu-opioids. The present study indicates that this tissue possesses mu, d and k-receptors with similar affinities to those found in other isolated tissue preparations, but has a small receptor reserve. Thus partial agonists such as morphine are detected as antagonists.

Animals↗

Effect of oral amrinone on platelet function and survival.

Amrinone is a cardiotonic agent associated with reversible thrombocytopenia in 20% to 50% of patients. The mechanism of thrombocytopenia is not known and it is not clear whether this effect represents a high-frequency idiosyncratic reaction or an overt manifestation of a toxic effect on platelet survival. We prospectively evaluated the effect of oral amrinone on platelet function and survival in seven subjects who participated in a clinical trial of chronic oral amrinone therapy. There was no consistent effect on either platelet function or platelet survival. Data suggest that amrinone does not have a uniform effect on platelet survival and that the development of thrombocytopenia may represent an idiosyncratic reaction.

Administration, Oral↗

Management of penetrating and blunt diaphragmatic injury.

The past 5 years' experience with diaphragmatic injuries at the University of Texas Health Science Center in San Antonio was reviewed to refine the clinical signs and appropriate treatment. During this period 102 patients were treated. Ninety-three patients incurred penetrating trauma to the diaphragm and nine patients suffered blunt trauma. Chest X-rays were normal in 40 patients, a hemo- and/or pneumothorax was present in 57, herniated abdominal viscera in four, and free air in one. Peritoneal lavage was positive in six of seven patients with blunt diaphragmatic injury, but was falsely negative in two of five patients (20%) with penetrating diaphragmatic injury. Eighty-nine patients (87%) experienced 137 associated injuries (excluding hemo- and/or pneumothorax). Nine patients (8.8%) had an isolated diaphragmatic injury. Four patients (4%) had a diaphragmatic injury associated with only a hemo- and/or pneumothorax. All patients, except for three with injuries recognized late, were operated upon immediately. Two patients had a missed diaphragmatic injury at initial laparotomy. There was one death in the series from a consumption coagulopathy. It was concluded that injuries to the diaphragm should be suspected in all patients with severe blunt torso trauma or with penetrating injuries near the diaphragm. Because of the nonspecificity of X-rays and the 20% false negative rate for peritoneal lavage, we believe that missed injuries and morbidity can be minimized by immediate laparotomy for all patients with abdominal and low thoracic penetrating injuries. Care must be taken not to overlook associated injuries.

Adolescent↗

Development of a monoclonal antibody capable of interacting with five serotypes of Staphylococcus aureus enterotoxin.

A monoclonal antibody capable of binding to determinants shared in common by staphylococcal enterotoxin serotypes A, B, C1, D, and E was developed. To accomplish this, BALB/c mice were immunized by alternating injections of serotypes A and D to enrich for spleen lymphocytes programmed to produce antibody to possible common determinants. These cells, fused with mutant myeloma cells (P3-X-63Ag8.653) produced hybrids that formed monoclonal antibodies to either serotype A only or to both serotypes A and D. A cloned hybridoma from the latter group produced an antibody (subclass immunoglobulin G1) which interacted with five serotypes. Highest affinity was to B and C1. An immunomatrix consisting of this antibody cross-linked to protein A-Sepharose CL-4B with dimethyl pimelimidate was capable of binding enterotoxin. Bound toxin was eluted with diethylamine. Because of its ability to interact with all five serotypes, the monoclonal antibody should prove useful in the development of a rapid method for screening foods for the presence of staphylococcal enterotoxin.

Animals↗

Effect of iron-deficiency anemia on hormone levels and thermoregulation during cold exposure.

When exposed to an ambient temperature of 4 degrees C, iron-deficient anemic rats become hypothermic. This lesion is related more to anemia than to tissue iron deficiency, since exchange transfusion to hematocrits over 25 restored normal thermoregulatory performance. Likewise poor cold responses were induced in control rats by transfusion to low hematocrits. Cold sensitivity in all anemic animals was paralleled by poor thyroid responses: there was a significant positive correlation between hematocrit and percent rise in triiodothyronine (r = 0.63) and thyroxine (r = 0.53) during 6 h at 4 degrees C. Basal levels of thyroid-stimulating hormone (TSH) were similar in control and iron-deficient animals: after cold exposure, TSH rose to higher levels in those animals with hematocrits over 25 than in those with lower hematocrits. Diminished O2 delivery to tissues responsible for heat production is probably a major component of the cold sensitivity of anemic rats. The novel finding that thyroid hormone responses are compromised by anemia implies effects on hormonal regulation that may also contribute to this functional lesion.

Anemia, Hypochromic↗

Neuropsychological concepts of somatoform disorders.

Clinical descriptions of somatoform disorders tend to fall largely into the two main categories of conversion disorder and hypochondriasis. These disorders frequently occur in the context of other psychopathology and also tend to have a significant association with CNS disease. Evidence implicating alterations in brainstem reticular arousal and attentional mechanisms in the etiology of these disorders is reviewed. Relevant studies investigating cerebral asymmetry of function have tended to associate right hemisphere information processing style with the sensory, attentional and affective changes that characterize conversion disorders. It is suggested that brain research in the field of somatoform disorders look to the second somatosensory area (SII), which appears to be especially suited to the types of neurophysiological and neuropsychological dynamics that are generally presumed to underlie this class of maladies. Finally, it is argued that a biopsychosocial approach to the understanding of somatoform disorders requires the incorporation of neuropsychological data into a multidimensional conceptual framework.

Arousal↗

Topical corticosteroids.

Topical corticosteroid therapy has revolutionised the management of many dermatological disorders. While treatment usually is effective there are problems associated with inappropriate therapy. This article reviews the availability and use of topical corticosteroid preparations in the treatment of common dermatological conditions.

Administration, Topical↗

X-ray analysis of the eye lens protein gamma-II crystallin at 1.9 A resolution.

We report the X-ray structure analysis and refinement at 1.9 A resolution of calf gamma-II crystallin, a lens-specific protein. The sequence of Croft (1972) has been modified to give a polypeptide chain of 174 residues (cf. 165). The protein has a symmetrical, hierarchical structure of two globular domains each comprising two similar "Greek key" motifs, consecutive along the polypeptide chain, and related by a pseudo 2-fold axis. The two domains pack together with a single connection and are related by a further pseudo 2-fold axis which bisects the angle between the intra-domain dyads. Forty-two pairs of C alpha positions for the two most similar motifs have root-mean-square separation at best fit of 0.69 A. The N and C-terminal domains gave root-mean-square separation of 0.89 A for 82 pairs of C alpha atoms at best fit. In each domain the two Greek key motifs form a pair of four-stranded antiparallel beta-pleated sheets, each sheet composed of three stands from one motif and one from the other. The sheets pack together in a wedge shape, closed at the top by the loops connecting the third and fourth strands of each motif. The first two strands of each motif form an extended beta-hairpin which is folded on to the beta-sheet. The packing of each motif into the globular domains involves a staggered bilayer of side-chains between each pair of beta-sheets which does not preserve the pseudo 2-fold axes observed in the C alpha position topology. In the core of each domain there are interactions between polarizable aromatic groups and sulphur-containing residues which may contribute to stability and may also serve to protect aromatic side-chains from ultraviolet light damage in the lens. At the surface of the molecule over half the ionic side-chains are closely paired, which probably stabilizes the tertiary fold and may reduce the water bound. Crystal lattice interactions are described which may be similar to those occurring in vivo in the lens between crystallins. Seven cysteine residues have been identified in the structure and these may have a role in the thermodynamic stability of the molecule, its intermolecular interactions under the normal reducing conditions of the lens, and also in the aggregation and cross-linking which occur in some forms of cataract. Three of these residues, Cys18, Cys23 and Cys74, form a cluster in the N-terminal domain.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

Multiple opiate receptors in the mouse vas deferens.

The agonist potencies of normorphine and [D-Ala2,D-Leu5]enkephalin (DADL) have been determined on the mouse vas deferens preparation under different conditions. Reducing the temperature at which the assay was performed had little effect on the response to DADL whilst the Emax of normorphine was greatly reduced. Tissues rendered tolerant to either agent exhibited little, if any, cross-tolerance to the other drug. The results suggest the presence of at least two types of opiate receptor in the mouse vas deferens.

Animals↗

A comparison of bupropion, dextroamphetamine, and placebo in mixed-substance abusers.

The subjective, behavioral, and physiological effects of bupropion, a nontricyclic antidepressant, were compared with those of dextroamphetamine and placebo in a randomized double-blind crossover study. The volunteers who participated were multiple-drug abusers. Six acute drug treatments, three doses of bupropion (100, 200, 400 mg), two doses of dextroamphetamine (15, 30 mg), and placebo were administered orally at intervals of not less than 72 h. Results indicated that the subjective effects of amphetamine as measured by the Addiction Research Center Inventory (ARCI) differed markedly from bupropion and placebo. Bupropion, in contrast to amphetamine, had no peripheral sympathomimetic effects and did not reduce appetite or caloric intake.

Adult↗

Effect of 5'-methylthioadenosine on RNA and DNA synthesis in cultured Xenopus laevis cells.

We have examined the effect of 5'-methylthioadenosine (MTA) on RNA metabolism and DNA synthesis in a cultured Xenopus laevis epithelial cell line. Cells incubated in the presence of MTA were transcriptionally less active than controls as measured by the run-off transcription technique. Experiments which measured the percentage of newly-synthesized poly(A)+ RNA and alpha-amanitin-sensitive nuclear transcripts suggested that MTA inhibited transcription by both RNA polymerases I and II. DNA synthesis was observed to proceed normally at times when MTA inhibited RNA synthesis. These results suggest that the well-known anti-proliferative effect of MTA is due indirectly to its initial effects on the transcription of ribosomal RNA (rRNA) and messenger RNA (mRNA) rather than a direct suppression of DNA replication.

Adenosine↗

Divergent structure activity relationships in series of enkephalin agonists and cognate antagonists.

Diallylation of the amino group of [Leu]enkephalin methyl ester yields a moderately potent, delta-selective opiate receptor antagonist. The diallyl congeners of a larger range of potent mu-and delta-selective enkephalin agonists have been prepared and were found to be weak, non-selective antagonists as assessed by their ability to antagonise the effects of normorphine and [Leu]enkephalin on the field-stimulated mouse vas deferens. Conversely, whereas [Gly3 psi (CH2S)Phe4,Leu5]enkephalin and [Gly3 psi(CH2S)-D-Phe4,Leu5]enkephalin are virtually inactive as opiate agonists the corresponding diallyl analogues are moderately potent, highly selective delta-antagonists. Analogues of diallyl[Leu]enkephalin in which the Gly2 and Gly3 residues have been replaced by D- and L- Ala have also been prepared and tested as delta-receptor antagonists. In addition, the empiric energy program ECEPP has been used to derive eighteen low energy conformations of diallyl[Leu]enkephalin and to estimate the effect of the D- and L-Ala substitutions on the conformer energies. Two conformers were identified for which there was a partial correlation between the variations in conformational energy and delta-antagonist potency.

Animals↗

A simplified method of esophageal pH monitoring for assessment of gastroesophageal reflux.

We have found that 24-hour esophageal pH monitoring is clinically useful in the evaluation of reflux-related symptoms but that the application of this diagnostic tool is limited by lack of simplicity and easy portability of equipment, a time-consuming method for data analysis, and the necessity to hospitalize patients for the study. We have resolved the first two problems with the development of a lightweight, portable, solid-state system for recording and analyzing the data. To assess the feasibility of utilizing an 8-hour study applicable to outpatients, we studied 30 unselected patients referred for 24-hour pH monitoring. We separately analyzed the data from the first 8 hours of the study and the data from the entire 24-hour period. The correlation between the results obtained with each analysis was excellent, indicating that the 8-hour study can be used to quantitate reflux accurately. An 8-hour outpatient protocol was developed and applied to 25 healthy volunteers to determine the normal range of values. From this, a simplified scoring system was created for assessing the results of 8-hour pH studies.

Adult↗

Red blood cell and serum selenium concentrations as influenced by age and selected diseases.

Red blood cell and serum selenium concentrations were investigated to determine normal concentrations for our geographic area and if potential differences existed in patients with selected diagnoses (hepatic, renal, malignant, and chronic diseases). Selenium was quantified in samples of red blood cells, serum and urine by neutron activation analysis. The results were analyzed by comparing 1) pooled data from all ages for each disease with normal values, and 2) normal values with age-matched patients in each disease category. Decreases in red blood cell selenium concentrations (P less than 0.05) occurred in normal subjects over 60 years of age without concurrent significant decreases in serum selenium. Although differential results were noted in age-matched groups, overall results showed that decreased concentrations of selenium in both red cells and in serum occurred with alcoholic cirrhosis, malignancies, and chronic renal failure (P less than 0.025). Red blood cell selenium concentrations also were decreased in patients with stable chronic disease. Decreased serum selenium concentrations were positively correlated with albumin concentrations in patients with cirrhosis. There was no correlation between serum selenium and bilirubin concentrations in patients with liver disease or between serum selenium and creatinine concentrations in patients with chronic renal failure whose urinary excretion of selenium was far below control levels.

Adult↗

A comparison of the effects of mezlocillin and carbenicillin on haemostasis in volunteers.

Mezlocillin and carbenicillin were administered intravenously to healthy male volunteers, for six days each, in a double-blind crossover study. Tests to detect abnormalities in haemostasis were performed before, during and after administration. Platelet aggregation studies indicated that both antibiotics interfered with platelet aggregation and secretion resulting in prolonged bleeding times. The effect was dose related and rapidly reversible after discontinuation of the antibiotics. It always occurred earlier and was more profound with carbenicillin than with mezlocillin (P = 0.008). Bleeding times greater than 15 min were observed in 17% of volunteers who received 18 g/day of mezlocillin and 83% of volunteers who received 18 g/day of carbenicillin (P less than 0.05). There were no abnormalities in the coagulation cascade. The risk of acquiring an antibiotic-induced clinical bleeding disorder is lower with mezlocillin than with carbenicillin.

Adenosine Diphosphate↗