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Biomedical subjects

M Hamilton

Publications and source records attributed to M Hamilton.

At least 127 records · Page 7Linked to original sources

Multiple idiopathic external root resorption.

An unusual case of multiple idiopathic root resorption involving all of the maxillary and mandibular incisor, canine, and premolar teeth is presented. A review of the literature reveals that this case is unusual in that, although other cases of multiple idiopathic root resorption have been described, the site of the resorption has been at the cervical margin in most reports, not at the apices as in this case. In other reports in which the resorption did affect the apices, the resorption usually affected only one, two, or three teeth. The pattern of resorption in this case, affecting only teeth with deciduous precursors, appears to be unique.

Adolescent↗

Placental transfer and fetal distribution of fluoxetine in the rat.

Previously conducted reproduction and teratology studies in rats (unpublished observations) exposed to fluoxetine have revealed no compound-related adverse effects on fertility and no teratogenic effects. In order to confirm embryonic/fetal exposure to fluoxetine and/or metabolites, dissection and whole-body autoradiographic techniques were utilized to determine the placental transfer and fetal distribution in 12- and 18-day-pregnant Wistar rats 1, 4, 8, and 24 hr following a single oral 12.5 mg/kg dose of [14C]fluoxetine. On gestation Days 12 (organogenesis) and 18 (postorganogenesis), peak concentrations of radiocarbon occurred 4-8 hr after dose administration in the placenta, embryo/fetus, amniotic fluid, and maternal kidney, brain, and lung, and declined slightly at 24 hr postdose. Maternal lung contained the highest tissue concentration of radiocarbon at all time points. Placenta and maternal brain, kidney, and liver contained moderate levels of radioactivity, while embryonic/fetal tissue, amniotic fluid, and maternal plasma contained low levels of radioactivity. Mean fetal concentrations of radiocarbon at 4, 8, and 24 hr on gestation Day 18 were higher than mean embryonic concentrations on Day 12 of gestation. Analytical characterization of radioactivity indicated that combined fluoxetine and norfluoxetine concentrations accounted for 63-80% of the total radiocarbon concentrations in embryonic/fetal tissue. Results indicated that embryonic/fetal and maternal tissue levels of fluoxetine were greatest at early time points and declined with time, while norfluoxetine tissue levels were highest at the 24-hr time point. Whole-body autoradiographic techniques demonstrated that radioactivity associated with [14C]fluoxetine and/or its metabolites traversed the placenta and distributed throughout the 18-day fetus 4 hr following dose administration. Visual and quantitative evaluations of the autoradiograms indicated that the highest fetal concentrations of radiocarbon were associated with brain and thymus. Results from these studies indicate that fluoxetine and norfluoxetine traverse the placenta and distribute within the embryo/fetus during the periods of organogenesis and postorganogenesis and confirm embryonic/fetal exposure of parent and metabolite in previous negative rat teratology and reproductive studies.

Animals↗

Frequency of symptoms in melancholia (depressive illness)

Symptoms of depression were quantitatively recorded using a rating scale, for 239 men and 260 women. The frequency of the various symptoms were similar for the sexes, with a high frequency for anxiety, both psychic and somatic. The results show that the symptoms of depressive patients differ from those found in the classic descriptions.

Affect↗

Clinical pharmacology of a novel diarylsulfonylurea anticancer agent.

LY186641 (diarylsulfonylurea, [DSU]) is a novel anticancer agent because of its unique diarylsulfonylurea chemical structure, broad-spectrum antisolid-tumor activity in preclinical models, presumed novel mechanism of action and preclinical toxicities of methemoglobinemia (Met Hgb) and decreased red blood cell (RBC) survival. In this study, the in vitro drug sensitivity of human tumors as well as clinical pharmacology and toxicology of DSU in patients with cancer were examined. DSU was administered orally, daily for 7 days with a 3-week treatment cycle. Dose-limiting toxicities were Met Hgb and RBC hemolysis. The maximum-tolerated dose was found to be 1,200 mg/m2/d for 7 days. In pharmacokinetic studies, DSU was found to have a prolonged serum half-life (approximately 30 hours) and a large area under the plasma disappearance curve (8,883.3 micrograms.hr/mL at 1,200 mg/m2/d). A partial remission was observed in one patient with refractory ovarian cancer. In conclusion, DSU can be safely administered to cancer patients and does display antitumor activity. Potential means of obviating the toxicities of this compound are discussed.

Adult↗

Pancreatic amylase measured in serum by use of a monoclonal antibody immunochemically immobilized to a solid phase.

We studied a method for measuring the pancreatic isoenzyme of amylase (EC 3.2.1.1) by use of a mouse monoclonal antibody against human salivary-type amylase (Clin Chem 1985;31:1283) coupled indirectly to particles of polyvinylidene fluoride via polyclonal goat anti-mouse immunoglobulin. These particles, in 200 microL of a suspension, could remove salivary amylase (activity 2200 U/L) from an equal volume of serum in 5 min. Measurement of amylase activity in the supernatant fluids from treated sera thus provided an assay of pancreatic amylase. Precision studies at three activity concentrations yielded within-run CVs of 1.6% to 1.7% (n = 25) and total CVs of 2.2% to 5.1% (20 days). Salivary amylase added to each of 10 sera was completely (99.8%, SD 1.6%) removed. The new method (y) showed the following regression statistics when compared with an electrophoretic method (x): slope = 0.989 (SD 0.019), intercept = -0.220% (SD 1.48%), SEE 4.0%, n = 51. Similar respective regression values were found for urine samples: slope = 0.934 (SD 0.053), intercept = 2.3 U/L (SD 3.2), SEE 8.4 U/L, n = 26. The following respective values were found when the new method (y) was compared with the previously described immunoprecipitation assay (x): slope = 1.02 (SD 0.02), intercept = 2.2% (SD 1.4%), SEE 3.3%, n = 23 sera. Reference intervals for pancreatic amylase activity in serum were established for three different substrates: maltotetraose, maltopentaose, and p-nitrophenylheptaoside.

Acute Disease↗

Cellularly defined minor histocompatibility antigens are differentially expressed on human hematopoietic progenitor cells.

Previously, five CTL lines directed against minor histocompatibility (mH) antigens designated HA-1-5 have been established from peripheral blood of patients after allogeneic bone marrow transplantation (BMT), and have been characterized using population and family studies. All cell lines showed specific HLA class I-restricted lysis of PHA-stimulated peripheral blood target cells from donors positive for the particular mH antigens. After 4 h of incubation of the mH antigen HA-3-specific CTL line with bone marrow cells from HA-3+ donors, complete class I-restricted inhibition of colony growth of the hematopoietic progenitor cells was observed even at low E/T ratios, indicating that the HA-3 antigen is strongly expressed on hematopoietic stem cells. Therefore, this antigen may be a target structure in the immune-mediated rejection of the hematopoietic graft in case of incompatibility for this determinant between donor and recipient in allogeneic BMT. In contrast, incubation of bone marrow cells with the antigen-specific anti-HA-1, -2, -4, and -5 CTL lines did not result in growth inhibition of the hematopoietic progenitor cells tested. After a prolonged incubation time and using a very high E/T ratio, progenitor cells from HA-2+ or HA-5+ donors were killed to some extent by the anti-mH-specific CTL lines, although the growth inhibition observed was minor and variable. Our results show that mH antigens are differentially expressed on human hematopoietic progenitor cells. Therefore, only some of these antigens may be targets in immune-mediated rejection of the bone marrow graft.

Cell Line↗

Liquid chromatographic determination of indolidan and its dehydro metabolite in plasma. Use of the Varian AASP for solid-phase extraction.

A method is described for the determination of indolidan and its dehydro metabolite in human plasma. Two procedures are given, one manual and one which is semi-automated by use of the Varian AASP (Automated Analytical Sample Processor). The method involves solid-phase extraction to isolate the drug, metabolite, and an internal standard from plasma. The manual procedure requires elution of the analytes from the extraction column with methanol, evaporation of the methanol to dryness, and reconstitution in mobile phase prior to injection into a reversed-phase liquid chromatographic system. Using the AASP (semi-automated procedure), the analytes are eluted from the extraction column directly into the chromatographic system, resulting in substantial savings in sample preparation time. The limit of detection for both drug and metabolite is 0.25 ng/ml in plasma. Detection was made by ultraviolet absorbance, using wavelength programming to optimize the sensitivity of the assay for each compound.

Autoanalysis↗

Abnormal sperm morphology and other semen parameters related to the outcome of the hamster oocyte human sperm penetration assay.

A new method for evaluation of sperm morphology using strict criteria is currently used in the andrology laboratory at the Eastern Virginia Medical School. A prospective study was designed to evaluate the following semen parameters in samples of all patients over a set period of time: sperm concentration and motility, and normal sperm morphology. These factors were correlated with results of the hamster zona-free oocyte/human sperm penetration assay (SPA). One hundred patients with a sperm concentration ranging from 2 to 219 X 10(6)/ml, a motile sperm fraction ranging from 6.9 to 87%, and normal sperm morphology ranging from 1 to 39%, were evaluated. The statistical analysis system general linear model was used to judge the influence of the different variables. There was a statistically significant relationship between the per cent of sperm with normal morphology and penetration rate in the SPA (P = 0.001). Outcome of the SPA was also correlated with in vitro fertilization, retrospectively, in 84 patients. Thirty-eight patients had an SPA less than 10%, with no fertilization in vitro in 13 patients (33.3%) and fertilization in 25 (66.7%). Forty-five had an SPA greater than 10% with fertilization in 37 (82.2%) and no fertilization in eight (17.8%) patients.

Animals↗

Evolution of a highly successful in vitro fertilization-embryo transfer program.

During the first 2 1/2 years of operation of the University of California at Los Angeles in vitro fertilization-embryo transfer program, 47 clinical pregnancies were achieved in 154 laparoscopies for oocyte aspiration (31%). Two of these pregnancies were achieved through transfer of cryopreserved embryos when ongoing pregnancy did not result from embryo transfer in the stimulated cycle. An increase in clinical implantation was noted with a reduction of transfer volume and proportion of air, with 34% of laparoscopies being followed by clinical pregnancy over the last 18 months. No difference in the rate of clinical pregnancy was noted relative to uterine depth or position. The high rate of multiple implantation (47%) suggested a high level of embryo quality. The success rate was attributed to a strong ovarian, human menopausal gonadotropin stimulation, accurate timing of human chorionic gonadotropin, a high oocyte retrieval rate, meticulous laboratory technique, atraumatic, high-fundal transfer of embryos, and initiation of embryo cryopreservation.

Embryo Transfer↗

Liquid chromatographic determination of pinacidil, a new antihypertensive drug, and its major metabolite, pinacidil N-oxide, in plasma.

Two procedures are described, one for the determination of pinacidil, the other for the determination of both pinacidil and its metabolite, pinacidil N-oxide, in plasma. When only parent drug levels are required, the plasma proteins are precipitated with acetonitrile, the solids discarded and the supernatant is evaporated to dryness. The residue is then reconstituted for analysis. For the determination of both drug and metabolite, the analytes are selectively retained from plasma on a solid-phase extraction column and eluted with methanol. After evaporation to dryness, the residue is reconstituted in mobile phase. Both procedures utilize reversed-phase liquid chromatographic separations with ultraviolet detection. The limits of detection are 10 ng/ml pinacidil in plasma and 5 ng/ml each of pinacidil and pinacidil N-oxide in plasma for the two procedures, respectively.

Antihypertensive Agents↗

Effect of cirrhosis and debrisoquin phenotype on the disposition and effects of pinacidil.

Pinacidil is an investigational vasodilator currently undergoing clinical trials as an antihypertensive agent. It is metabolized in humans to pinacidil N-oxide. To determine whether pinacidil's metabolism or effects were influenced by either liver disease or the subject's debrisoquin phenotype, eight patients with chronic stable cirrhosis and 13 healthy subjects were studied. Seven of the healthy volunteers were extensive metabolizers of debrisoquin, whereas six were of the poor metabolizer phenotype. Neither the clearance of pinacidil nor the production of the N-oxide was altered by the subjects' debrisoquin phenotype. Cirrhosis produced a 50% reduction in pinacidil's clearance (20.7 +/- 1.4 vs. 42.1 +/- 5.1 L/hr; P less than 0.0005) and a prolongation in the elimination t1/2 from 3.9 +/- 0.3 to 6.1 +/- 0.6 hours (P less than 0.01). Less pinacidil was metabolized to the N-oxide metabolite in the patients with cirrhosis than in the normal individuals. Thus pinacidil's metabolism and clearance are reduced in patients with cirrhosis but are independent of debrisoquin phenotype.

Adult↗

Electroconvulsive therapy. Indications and contraindications.

The indications for convulsive treatment are such that, when it is properly used, it is one of the most effective treatments in the whole of medicine. Its chief indication is for depressive illness that shows predominantly biological features. It is particularly useful for patients who have not responded to other treatments and for those who are actively suicidal. Research on the prediction of response has yielded very little information beyond that already based on clinical experience. In the right conditions it is remarkably safe and has few contraindications. In a way it corresponds to a "surgical" treatment and, therefore, it is to be hoped that when its mode of action is adequately elucidated, it will be replaced by "medical" treatments.

Bipolar Disorder↗

Depression in the fifties.

'Depression in the fifties' is assumed to signify 'involutional melancholia', a diagnosis which was once much used but is now disappearing. It has been proposed that this category arose from what was essentially a comparison between unipolar and bipolar depressions but which ignored the differences in the modal age of onset.

Age Factors↗