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Biomedical subjects

W K Smith

Publications and source records attributed to W K Smith.

At least 19 recordsLinked to original sources

Gestational weight gain, pregnancy outcome, and postpartum weight retention.

OBJECTIVE: To determine whether the risk of maternal overweight associated with an excessive rate of gestational gain needs to be balanced against the risks of impaired fetal growth associated with a low rate of gain. METHODS: Rate of gestational weight gain was measured prospectively in a sample of 274 young, low-income, and primarily minority women (12-29 years old) with pregravid body mass indices (BMI) in the normal range (19.8-26.0). We defined an excessive rate of gain between 20-36 weeks' gestation as one greater than 0.68 kg/week, and a low rate of gain as one less than 0.34 kg/week. Women were followed-up at 4-6 weeks and 6 months postpartum. RESULTS: Rate of measured gestational gain between 20-36 weeks' gestation was associated with total weight gain based on pregravid weight, with infant birth weight and gestation duration, and with maternal overweight (BMI greater than 26) and weight retention postpartum. Infant birth weight and gestation duration were significantly reduced for women with low rates of gain, and there was no significant difference between women with excessive and moderate gains. Despite little difference in pregravid BMI, women with excessive rates of gain retained more weight overall, attained a greater postpartum BMI, and had higher levels of subcutaneous fat and overweight. Maternal anthropometric status showed little change between 4-6 weeks and 6 months postpartum. CONCLUSION: Weight gained at an excessive rate by women with a pregravid BMI in the normal range does not greatly enhance fetal growth and gestation duration, contributing instead to postpartum maternal overweight.

Adolescent

Disease-specific patterns of locus coeruleus cell loss.

Computer visualization techniques were used to map and to quantitatively reconstruct the entire locus coeruleus, including the nucleus subcoeruleus, to compare the topographic patterns of cell loss in postmortem brains from patients with Parkinson's disease, Alzheimer's disease, and Down syndrome. There was comparable cell loss in all three diseases (approximately 60%) compared with aged normal subjects, and there was a significant loss of nucleus subcoeruleus cells specifically in patients with Parkinson's disease (63%). There was a significant positive correlation between the magnitude of locus coeruleus cell loss and the duration of Alzheimer's disease, but no such correlation was found for Parkinson's disease. In patients with Parkinson's disease, there was comparable cell loss throughout the rostral-caudal extent of the nucleus; however, in patients with Alzheimer's disease and Down syndrome, the greatest cell loss always occurred within the rostral portion of the nucleus, with a relative sparing of caudal cells. These data are consistent with the hypothesis that cell loss in Parkinson's disease is the result of a pathological process that attacks the catecholaminergic cells of the locus coeruleus and the subcoeruleus in general; in Alzheimer's disease and Down syndrome, however, the pathological process only affects the rostral, cortical-projecting locus coeruleus cells and spares the caudal, noncortical-projecting cells.

Aged

Analgesic efficacy of bromfenac, ibuprofen, and aspirin in postoperative oral surgery pain.

We recently demonstrated that 25 mg of bromfenac, a new nonsteroidal anti-inflammatory analgesic, is at least as effective as 400 mg of ibuprofen in relieving postoperative oral surgery pain. Our objective in this study was to determine whether higher doses were significantly more effective. Two hundred eighty (280) outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double-blind basis, a single oral dose of 10, 25, 50, or 100 mg bromfenac; 650 mg aspirin; 400 mg ibuprofen; or placebo. Subjects rated their pain and its relief for 8 hours. All active treatments were significantly superior to placebo, and bromfenac and ibuprofen were significantly superior to aspirin. The slope of the dose-response curve of bromfenac was significant. The 100 mg bromfenac dose was significantly more effective than the 400 mg ibuprofen dose and had a significantly longer duration of analgesic action.

Aspirin

Effect of caffeine on ibuprofen analgesia in postoperative oral surgery pain.

Recent studies have demonstrated that caffeine acts as an analgesic adjuvant when combined with acetaminophen, aspirin, or their mixture. Our objective was to determine whether similar enhancement of analgesia could be demonstrated when caffeine is combined with ibuprofen. On a double-blind basis, a single oral dose of ibuprofen (50, 100, or 200 mg), a combination of ibuprofen, 100 mg, with caffeine, 100 mg, a combination of ibuprofen, 200 mg, with caffeine, 100 mg, or placebo was randomly assigned to 298 outpatients with postoperative pain after the surgical removal of impacted third molars. With a self-rating record, subjects rated their pain and its relief hourly for 8 hours. All active treatments were significantly superior to placebo, and the caffeine effect was significant for every measure of analgesia. Relative potency estimates indicated that the combination was 2.4 to 2.8 times as potent as ibuprofen alone. The combination also had a more rapid onset and longer duration of analgesic action. The analgesic adjuvancy of caffeine clearly extends to combinations with nonsteroidal anti-inflammatory drugs other than acetaminophen or aspirin.

Adolescent

Evaluation of aspirin, caffeine, and their combination in postoperative oral surgery pain.

Three hundred fifty outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double-blind basis, to receive a single oral dose of aspirin 650 or 1000 mg, caffeine 65 mg, a combination of aspirin 650 mg with caffeine 65 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 6 hours after medicating. Estimates of summed pain intensity difference, peak pain intensity difference, total relief, peak relief, and hours of 50% relief were derived from these subjective reports. All active treatments except caffeine were significantly superior to placebo. Pairwise comparisons indicated the aspirin-caffeine combination was statistically superior to aspirin 650 mg alone for hours of 50% relief among patients who had severe baseline pain. Adverse effects were transitory and none were serious.

Administration, Oral

Computer-assisted three-dimensional reconstructions of [14C]-2-deoxy-D-glucose metabolism in cat lumbosacral spinal cord following cutaneous stimulation of the hindfoot.

We report on computer-assisted three-dimensional reconstruction of spinal cord activity associated with stimulation of the plantar cushion (PC) as revealed by [14C]-2-deoxy-D-glucose (2-DG) serial autoradiographs. Moderate PC stimulation in cats elicits a reflex phasic plantar flexion of the toes. Four cats were chronically spinalized at about T6 under barbiturate anesthesia. Four to 11 days later, the cats were injected (i.v.) with 2-DG (100 microCi/kg) and the PC was electrically stimulated with needle electrodes at 2-5 times threshold for eliciting a reflex. Following stimulation, the spinal cord was processed for autoradiography. Subsequently, autoradiographs, representing approximately 8-18 mm from spinal segments L6-S1, were digitized for computer analysis and 3-D reconstruction. Several strategies of analysis were employed: 1) Three-dimensional volume images were color-coded to represent different levels of functional activity. 2) On the reconstructed volumes, "virtual" sections were made in the horizontal, sagittal, and transverse planes to view regions of 2-DG activity. 3) In addition, we were able to sample different regions within the grey and white matter semi-quantitatively (i.e., pixel intensity) from section to section to reveal differences between ipsi- and contralateral activity, as well as possible variation between sections. These analyses revealed 2-DG activity associated with moderate PC stimulation, not only in the ipsilateral dorsal horn as we had previously demonstrated, but also in both the ipsilateral and contralateral ventral horns, as well as in the intermediate grey matter. The use of novel computer analysis techniques--combined with an unanesthetized preparation--enabled us to demonstrate that the increased metabolic activity in the lumbosacral spinal cord associated with PC stimulation was much more extensive than had heretofore been observed.

Animals

1-Methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'CH3-MPTP)-induced degeneration of mesostriatal dopaminergic neurons in the mouse: biochemical and neuroanatomical studies.

The neurotoxic effects of 1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'CH3-MPTP), a substituted analog of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, were studied in BALB/cJ mice. Moderate doses of 2'CH3-MPTP produced a greater depletion of dopamine (DA) in the striatum (45%) than in the nucleus accumbens (23%), and in these same animals, there was a 35% loss of midbrain DA neurons. The greatest loss of DA cells occurred within the substantia nigra (43%), and there was also a significant loss of cells within the ventral tegmental area (28%). Higher doses of 2'CH3-MPTP decreased levels of DA more in the axon terminal/forebrain region (72%) than in the cell body/midbrain region (25%). Similar forebrain/midbrain DA depletion ratios were also found in mice that received an electrolytic lesion of the midbrain DA neurons; there was a greater Da depletion in the forebrain (29%) than in the midbrain (8%). In both 2'CH3-MPTP and electrolytically lesioned animals there was a significant increase in DA turnover in the forebrain region, as measured by the homovanillic acid/DA ratio. These data indicate that 2'CH3-MPTP: (1) destroys DA neurons within two midbrain regions containing cells which project to the striatum (i.e. mesostriatal DA neurons), rather than just nigrostriatal DA neurons; (2) produces a greater loss of DA in the axon terminal region than in the cell body region; and (3) influences the mesostriatal DA neurons in the same way as does a lesion to the cell bodies. These data are discussed with regard to the pathophysiology of 2'CH3-MPTP.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Midbrain dopaminergic cell loss in Parkinson's disease: computer visualization.

Computer visualization techniques were used to map the distribution of dopaminergic neurons within midbrain tissue sections from 5 parkinsonian patients and 3 age-matched control subjects. The Parkinsonian brains had over 50% fewer dopaminergic neurons within the midbrain than age-matched normal brains. The cell loss occurred within the combined substantia nigra (dopaminergic nucleus A9) and retrorubral (dopaminergic nucleus A8) areas (greater than 61%) and the ventral tegmental area (dopaminergic nucleus A10) (greater than 42%). The cell loss was greatest within the ventral portion of the substantia nigra zona compacta. The specific pattern of cell loss is very similar to the pattern of cells that project to the striatum (as opposed to cortical and limbic sites) in animal neuroanatomical tracing experiments. These data suggest that Parkinson's disease preferentially destroys midbrain dopaminergic neurons in nuclei A8, A9, and A10, which project to the striatum.

Aged

The human locus coeruleus: computer reconstruction of cellular distribution.

Quantitative neuroanatomical techniques were developed to map the distribution of norepinephrine-containing locus coeruleus (LC) neurons in the adult human brain. These neurons reside in the dorsolateral pontine tegmentum and are identifiable by their neuromelanin pigment content. Five brains, ranging in age from 60 to 104 years, were examined. Outlines of coronal or sagittal sections containing the LC were entered into a computer along with the location of each cell, certain neuroanatomical landmarks, and cell size. Sections were aligned with specific neuroanatomical landmarks so that the computer-generated distribution of cells was representative of the in situ distribution of cells. Analysis of (1) the number of cells in sections throughout the rostrocaudal extent of the nucleus, (2) cell size, (3) 3-dimensional reconstructions of the distribution of cells within the brain stem, and (4) 2-dimensional cell-frequency maps, make it possible to quantitatively characterize the distribution of cells within this large nucleus. The total estimated number of LC cells on both sides of the brain ranged from 45,562 to 18,940 (youngest to oldest), and mean soma area ranged from 835 to 718 micron 2 (youngest to oldest). The nucleus is "tube-like" in shape, has a rostrocaudal extent of approximately 16 mm, and is bilaterally symmetrical. Two-dimensional cell-frequency maps were developed to illustrate the regional distribution of cell frequencies at any rostrocaudal/mediolateral point on the horizontal plane; the total unilateral area of the LC ranged from 32.8 to 17.2 mm2 (youngest to oldest). The techniques developed to characterize the 2- and 3-dimensional distributions of LC neurons can be used in future studies to quantitatively examine the effects of aging and disease on this and other brain nuclei.

Cell Count

The stress analogy.

The author calls attention to the advantages of using the engineering meaning of stress and strain when applying these terms to describe the effects of social and physical forces on people. Such an analogy opens up the possibility of measuring the amount of damage from excess stresses existing in people, as well as estimating their limits and remaining strengths. It also explains why some people are more affected by a given stressor than other people.

General Adaptation Syndrome

Rat medulla oblongata. IV. Topographical distribution of catecholaminergic neurons with quantitative three-dimensional computer reconstruction.

We examined serial 40 micron vibratome, immunoperoxidase-stained sections of the medulla with tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), and phenylethanolamine N-methyltransferase (PNMT) antisera followed by Nissl staining to locate catecholaminergic neurons in cytoarchitectonic regions followed by a three-dimensional (3D) computer reconstruction of these cell groups to determine their spatial organization. Overlay drawings of low and high power photomicrographs showing cell bodies and nuclear boundaries were entered into a digital computer storage system. Every section in the series was plotted to yield an accurate representation of regional densities of cells and location of nuclei, as revealed by two-dimensional plots of individual sections as well as three-dimensional plots of groups of sections. Data files were scanned in a number of ways to obtain total cell counts of TH-, DBH-, and PNMT-immunoreactive cells within a designated area or cell counts of only one type of immunoreactive cell. This combination of data manipulation produced the following results: (1) A1 group is a homogeneous population of noradrenergic neurons at levels caudal to the obex, and at the obex it is mixed with adrenergic cells. The dimensions of the A1 cell group are 1.3 X 2.7 mm, extending from -2.5 to +0.2. Part of this cell group lies in the lateral reticular nucleus. (2) A2 group is not purely noradrenergic as previously suspected. It is a very mixed cell group containing mainly dopaminergic neurons in the area postrema (periventricular region) and the dorsal motor nucleus of the vagus, mainly noradrenergic neurons in the medial subnucleus of the nucleus of the tractus solitarius (nTS), mainly adrenergic neurons in the dorsal strip and dorsal subnucleus of the nucleus of the tractus solitarius, and a mixture of all three catecholaminergic neurons in the other subnuclei of the nTS. The dimensions of this group are 0.4 X 3 mm extending from -2.7 to +0.3. (3) C1 group is a homogeneous population of adrenaline cells extending from +1 to +2.5 with dimensions of 1.5 X 1.5 mm and consisting of scattered neurons some of which occupy the gigantocellular reticular nucleus. (4) C2 group is a homogeneous population of adrenaline neurons extending from +1 to +3 with dimensions of 2.5 X 3 mm. Accurate visual imaging and quantitation of the spatial organization of medullary catecholaminergic neurons within the classical anatomical framework of cytoarchitecture provides an enhanced comprehension of the organization of this region of the central nervous system.

Animals

A renal countercurrent system in marine elasmobranch fish: a computer-assisted reconstruction.

Computer-aided techniques were used to reconstruct the complex renal tubular system in the dorsal kidney region of a marine elasmobranch fish, the little skate (Raja erinacea), from a series of light micrographs of serial sections. It was established that five individual segments of one nephron, consisting of two loops and a distal tubule, are arranged in parallel within an elongated closed tissue sac. Capillaries, which form a network around these nephron segments, enter and exit this sac at the same end. This anatomical arrangement suggests that a complex renal countercurrent multiplier system may be important in fluid regulation in these fish.

Animals

Mucosal nerves and smooth muscle relationships with gastric glands of the opossum: an ultrastructural and three-dimensional reconstruction study.

The precise anatomical relation by which autonomic nerve endings contact gastric epithelial cells to enhance the rate of gastric secretions is not fully understood. The aim of the present study was to clarify this issue by using the technique of serial section reconstruction of areas of the gastric mucosa. The work also explored the possibility of a functional role for a system of smooth muscle strands in the gastric mucosa that emanate from the muscularis mucosa, run in the lamina propria, and are associated in a unique manner with the gastric glands. Electron microscopic serial sections of the gastric mucosa were performed to visualize the entire limiting membrane of gastric epithelial cells to determine any nerve associations (especially varicose endings) with these cells. Evaluation of serial sections of five separate parietal cells showed that their basal membrane did not come in close contact (nearest distance 500 nm) with any nerve axon or varicosity. Moreover, the axons passing in the area of these cells ultimately showed varicose endings associated with smooth muscle cells in the adjacent connective tissue (often separated by only 20 nm), with mast cells or with vascular elements. Additionally, the lateral membrane of these five parietal cells did not contact any endocrine cell in the epithelium, although other parietal cells in the area were adjacent to endocrine cells. Chief cells in the immediate area also did not form any close associations with nerve varicosities. Random analysis of 5,000 additional epithelial cells in these sections showed no close associations to nerve elements with significant accumulations of neurosecretory vesicles (varicosities). Because of the observed existence of innervation to the smooth muscle strands in the area of the gastric glands, serial 1-micron epoxy sections of the gastric mucosa were prepared, and profiles of smooth muscle and gastric glands were entered into a computer-assisted reconstruction system. Three-dimensional reconstruction techniques were employed to reveal the existence of a unique association between the mucosal smooth muscle strands and the gastric glands. The muscle strands arose from the muscularis mucosa at regular intervals and became branched to form an intricate wrap around a series of gastric glands that empty into one gastric pit.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Transfusion-acquired cytomegalovirus infection in cardiac surgery patients.

The incidence of transfusion-acquired primary cytomegalovirus (CMV) infection was studied in 483 cardiac surgery patients. Ninety-six patients (20%) were found to lack antibody to CMV [CMV Ab(-)] as measured by radioimmunoassay. Sixty-eight CMV Ab(-) were followed by viral culture and/or serology from eight weeks to one year after transfusion. Transfusion requirements in CMV Ab(-) patients were as follows: whole blood/packed red blood cells, mean 4.7 +/- 2.6 units; platelets (20 patients), 6.9 +/- 3.8 units; fresh frozen plasma (25 patients), mean 3.3 +/- 1.6 units. Forty-nine percent of 235 donor units tested had antibody to CMV. One donor unit (0.4%) had CMV-specific IgM. This was not associated with CMV infection in the recipient. One patient (1.5%) demonstrated evidence of seroconversion to CMV during the follow-up period. This is significantly less than reported in previously published studies (P less than .01). Serological methods used, the age of the transfused blood, the immune status of the transfusion recipient, and the administration of passive antibody in fresh frozen plasma are factors that may be responsible for the low incidence observed.

Antibodies, Viral

Interferon enhances antibody-dependent cellular cytotoxicity when suboptimal concentrations of antibody are used.

Polymorphonuclear leukocytes (PMN) and killer (K) cells isolated from buffy coats from normal volunteers were tested for antibody-dependent cellular cytotoxicity (ADCC) against chicken erythrocytes (CRBC) with and without the addition of interferon (IFN). Maximum enhancing activity was found when the anti-CRBC antibodies in the ADCC reaction were at suboptimal concentrations. All three species of pure recombinant Escherichia coli-derived interferon were compared for their ability to enhance ADCC in both effector systems. Recombinant IFN-gamma was found to be effective at lower doses than recombinant IFN-alpha A or recombinant IFN-beta, although maximum activity for all three species was similar in the PMN system. IFN-gamma also enhanced K-cell ADCC but to a lesser extent than in the PMN system. There appeared to be individual variation in response of the K-cell ADCC system to IFN-alpha A and IFN-beta at the doses tested.

Animals

The synthesis and accumulation of cholesteryl esters by the developing embryo of the domestic fowl.

A comparative study has been made of the accumulation and synthesis of cholesteryl esters in the liver, yolk sac membrane, and yolk contents of the chick embryo during the last week of development. This involved a comparison of the cholesteryl esters synthesized during incubation in vitro with 14C-cholesterol with those accumulated during incubation in vivo. Results indicated that the considerable accumulation of cholesteryl esters, mainly cholesteryl oleate, that occurred within the liver during embryo development arose from synthesis in the yolk sac membrane. This suggested a specific role in the transport of yolk lipid into the embryo. With the approach of hatching the ability of the liver to synthesize its own cholesteryl esters increased while that of the yolk sac membrane decreased.

Animals