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Biomedical subjects

D L Smith

Publications and source records attributed to D L Smith.

At least 325 records · Page 18Linked to original sources

Clinical differences among nonsteroidal antiinflammatory drugs: implications for therapeutic substitution in ambulatory patients.

The practice of therapeutic substitution, i.e., replacing one drug with another chemically different drug from the same therapeutic class, represents an important therapeutic modification with potential clinical significance far beyond that of generic substitution. Adverse consequences following therapeutic substitution of nonsteroidal antiinflammatory drugs (NSAID) is of special concern because of substantial differences among these agents in pharmacokinetic, pharmacological, and clinical properties. Therapeutic substitution of NSAID for ambulatory patients may result in compromised clinical outcome because (1) patient response is unpredictable and selection of the optimal agent must be tailored for each patient; (2) substantial differences exist in adverse reaction profiles; (3) drug interaction studies are lacking; and (4) selection of an agent must be individualized to ensure compliance with the dosing regimen. Cost savings achieved through therapeutic substitution of NSAID may be lost by additional overall treatment costs due to adverse reactions or suboptimal therapy. The occurrence of adverse or suboptimal effects in ambulatory patients is more likely if NSAID are substituted without full knowledge of the patient's medical history and clinical status. Communication between the pharmacy and prescribing physician regarding a patient's specific needs is essential for rational substitution among NSAID.

Ambulatory Care↗

Absorption of calcium and magnesium from fortified human milk by very low birth weight infants.

Absorption of calcium and magnesium endogenous to human milk, as well as calcium and magnesium added as an exogenous supplement to human milk, was determined in 9 very low birth wt infants. Human milk, intrinsically labeled with stable isotopic tracers of calcium and magnesium, was prepared by administering isotopic tracers intravenously to a lactating woman. Different isotopic tracers, which were representative of calcium and magnesium in the supplement (Enfamil Human Milk Fortifier, Mead Johnson Nutritional Div.), were added to the intrinsically labeled milk. The fortified milk, which was labeled with two calcium tracers and two magnesium tracers, was given orally to the test subjects in a single feeding. True absorption of calcium and magnesium was determined from differences between the doses of tracer ingested and the quantities of tracer excreted in the feces. Stable isotopic tracers were quantified by fast atom bombardment mass spectrometry. These results demonstrate that the fractional absorptions of calcium in the human milk and the added mineral supplement are 80 and 82%, respectively. A total of 89% magnesium endogenous to human milk and 86% of magnesium derived from the mineral supplement was absorbed by the VLBW infants.

Biological Availability↗

Release of somatic embryogenic potential from excised zygotic embryos of carrot and maintenance of proembryonic cultures in hormone-free medium.

Excised zygotic embryos, mericarps ("seeds") and hypocotyls of seedlings of cultivated carrot Daucus carota cv. Scarlet Nantes were evaluated for their ability to generate somatic embryos on a semisolid hormone-free nutrient medium. Neither intact zygotic embryos nor hypocotyls ever produced somatic embryos. However, mericarps and broken zygotic embryos were excellent sources for somatic embryo production (response levels as high as 86%). Somatic embryo formation was highest from cotyledons, but was also observed on isolated hypocotyls and root tips of mature zygotic embryos. On media containing unreduced nitrogen, somatic embryo formation led to the generation of vigorous cultures comprised entirely of somatic embryos at various stages of development which in turn proliferated still other somatic embryos. However, a medium was devised which when 1-5 mM NH4+ was the sole nitrogen source, led only to a proliferation of globular proembryos. Sustained subculturing of these proembryos at 2-3 week intervals enabled establishment of highly uniform cultures in which no further development into more mature stages of embryonic development occurred. These have been maintained, without decline, as morphogenetically competent proembryonic globules for over ten months. A basal medium containing from 1-5 mM NH4+ as the sole nitrogen source appears not to be inductive to somatic proembryo formation. Instead, such a medium is best thought of as permissive to the expression of embryogenically determined cells within zygotic embryos. By excising and breaking or wounding zygotic embryos, constituent cells are probably released from positional or chemical restraints and thus are able to express their innate embryogenic potential. Once a proembryonic culture is established, this medium containing 1-5 mM NH4+ as the sole nitrogen source provides a nonpermissive environment to the development and growth of later embryonic stages, but it does allow the continued formation and multiplication of globular somatic proembryos. The sequence of events leading from excised broken zygotic embryos to the formation of somatic embryos and the maintenance of somatic proembryos are demonstrated by scanning electron microscopy and histological preparations. Germination levels from intact zygotic embryos on media with varying levels and ratios of unreduced vs. reduced inorganic nitrogen were determined as well and provided baseline or control data on the type of response obtained from nonwounded material.

Ammonium Chloride↗

Synovial fluid lymphocytes in eosinophilic fasciitis.

Arthritis is an uncommon manifestation of eosinophilic fasciitis. We report a patient who developed arthritis of his left knee, followed 2 weeks later by skin lesions which evolved into histologically proven eosinophilic fasciitis. Synovianalysis on 2 occasions demonstrated a mildly inflammatory fluid with more than 90% lymphocytes. These lymphocytes were shown to be primarily activated suppressor/cytotoxic T cells.

Adult↗

Treatment of nonseptic olecranon bursitis. A controlled, blinded prospective trial.

We enrolled 42 patients with nonseptic olecranon bursitis in a double-blind prospective treatment trial to compare the efficacy of an intrabursal steroid preparation with that of an oral anti-inflammatory agent. Patients were randomized into one of four treatment regimens: (1) methylprednisolone acetate (20 mg) intrabursal injection and oral naproxen (1 g/d for 10 days), (2) methylprednisolone acetate (20 mg) intrabursal injection and oral placebo for 10 days, (3) oral naproxen (1 g/d for 10 days), and (4) oral placebo for 10 days. The degree of swelling in millimeters was assessed at study introduction and at 1, 3, and 6 weeks. At 6 months, the number of patients requiring reaspiration for bursitis recurrence was tabulated. Data at 1 week indicated that patients treated with an intrabursal methylprednisolone acetate injection (20 mg) demonstrated the most rapid decrease in swelling. At 6 weeks, the methylprednisolone-treated groups demonstrated sustained improvement. At 6 months, the mean number of reaspirations per patient for reaccumulation of bursal fluid was higher in groups 3 (1.0 +/- 1.2) and 4 (0.4 +/- 0.7). An intrabursal methylprednisolone acetate 20-mg injection seems to be the most effective treatment regimen for nonseptic olecranon bursitis.

Administration, Oral↗

Therapeutic impact of eicosanoids in atherosclerotic disease.

Polyunsaturated fatty acid (PUFA) components of the diet, especially of the omega-3 variety, protect against atherosclerosis and its related thrombotic complications. Mechanisms involved probably involve the eicosanoids. Classic PGE1 has now found a role in the treatment of peripheral vascular disease. Prostacyclin (PGI2) discovered over ten years ago has also been introduced into clinical medicine; orally active analogs are being introduced with clinical potential in a variety of atherosclerotic and thrombotic disorders. "Endothelium-derived relaxing factor (EDRF)" has been identified with nitric oxide, an active metabolite of the classic nitrodilator compounds, which (like NO itself) is synergistic with prostacyclins in inhibition of platelet activation, but without similar synergistic effects on vasodilation. This finding is of considerable importance both from physiological and therapeutic standpoints. The therapeutic efficacy of acetylsalicylic acid (ASA, aspirin) in the secondary prevention of myocardial infarction is now established. For primary prevention, it is probably inferior to diet (e.g. fish oil) and lifestyle changes due to increased incidence of cerebrovascular bleeding. The unfulfilled therapeutic promise of thromboxane synthesis inhibitors may be overcome by introduction of dual TX receptor/synthesis inhibitors. Recent advances suggest that PGE1, prostacyclin analogs and high dose fish oil could act beneficially against background nitrodilator therapy in preventing thrombosis and mitogen-stimulated restenosis following thrombolytic or surgical treatment of coronary artery occlusion.

Animals↗

Pseudallescheria boydii brain abscess: association with near-drowning and efficacy of high-dose, prolonged miconazole therapy in patients with multiple abscesses.

Brain abscess caused by Pseudallescheria boydii is a highly lethal infection, usually seen in immunosuppressed patients. Five patients with P. boydii brain abscesses are described. Four of these patients acquired their infection after near-drowning; 1 patient developed an abscess after penetrating head trauma. Two patients survived their infections, which included involvement of other body sites (lung, eye, bone) as well as multiple undrained brain abscesses, after prolonged courses of high-dose parenteral miconazole (80-90 mg/kg/d). Progressive increases in miconazole dosage during the treatment periods were required to produce serum levels above the minimum inhibitory concentrations of the fungal isolates.

Adult↗

Mechanisms responsible for inhibition of vein-graft arteriosclerosis by fish oil.

Favorable changes in lipoproteins, inhibition of platelet aggregation, reduction of serum thromboxane (TX), altered plasma-membrane fluidity, and reduced production of growth factors (mitogens) have all been implicated as possibly being involved in the inhibition of arteriosclerosis by fish oil (FO), which is rich in omega 3 fatty acids; however, causal relations are mostly lacking. Several putative mechanisms responsible for the salutary effects of FO were investigated in a canine model of accelerated vein-graft arteriosclerosis. Venoarterial autografts (N = 192) were implanted in 48 hypercholesterolemic dogs divided into six groups: group A, control; B, FO (as MaxEPA, 200 mg/kg/day eicosapentaenoic acid); C, aspirin (ASA, 50 mg/kg/day); D, TX synthetase inhibitor (TXSI [CGS-12970], 10 mg/kg/day); E, FO + ASA; and F, FO + TXSI. At sacrifice 3 months later, there was no significant difference in plasma lipoproteins, hepatic low density lipoprotein-receptor concentration, red blood cell fragility, bleeding time, or platelet count compared with controls; the decrease in platelet aggregation (30 +/- 5% [mean +/- SEM]) was similar in all treatment groups. Arterialized vein-graft intimal thickening was significantly inhibited by FO (with or without ASA), while ASA alone was ineffective. Conversely, serum TX was significantly lower only in the ASA and FO + ASA groups. Serum mitogenic activity was higher at 3 months in the control group versus all treatment groups. Compared with baseline values, serum mitogenic activity rose significantly over time in the control and the TXSI groups, and an increase or rising trend was present in all other treatment groups except for the FO-treated animals. Thus, the salutary biologic effect of FO in this hypercholesterolemic model of arterialized vein grafts may have been more related to in vivo inhibition of platelet-mitogen growth factor release than to changes in lipoproteins, low density lipoprotein receptors, platelet function, or eicosanoid metabolism. These observations underscore the need for further studies to clarify the interactions between FO (omega 3 fatty acids) and paracrine cellular mitogenic factors in the context of atherosclerosis prevention.

Animals↗

The effects of exercise on intraocular pressure in pigmentary glaucoma patients.

Previous studies of normal volunteers and open-angle glaucoma patients have shown that exercise temporarily lowers intraocular pressure. However, two case reports have described pigmentary dispersion syndrome patients who developed symptomatic increased intraocular pressure after exercise. We evaluated the intraocular pressure response to exercise in ten pigmentary glaucoma patients. An exercise protocol was designed to increase the likelihood of lens zonule-iris pigment epithelium contact. Intraocular pressure measurements during the first two hours after exercise showed no statistically significant elevation of mean intraocular pressure. The pressure rose 6 mm Hg and 7 mm Hg respectively at 15 minutes in two eyes, but returned to baseline by 30 minutes. Our results suggest that exercise may not significantly increase the clinical intraocular pressure in pigmentary glaucoma patients.

Adult↗

Cardiovascular effects of indapamide in hypertensive patients with or without renal failure. A dose-response curve.

Fifteen patients with mild-to-moderate hypertension (10 with normal and five with decreased renal function) were studied after treatment with placebo and low (1 mg), intermediate (2.5 mg), and high (5.0 mg per day) doses of indapamide, each for four weeks. Six patients--five with normal renal function--were classified as nonresponders (decrease in diastolic blood pressure less than 5 mm Hg). The remaining nine patients had dose-related decreases in blood pressure. Patients with or without renal failure showed similar decreases in blood pressure. Blood pressure reduction was associated with a significant decrease in cardiac index in the responders at the highest dose, related to a decrease in left ventricular end-diastolic dimension and stroke volume, whereas heart rate did not increase. This apparent decrease in venous return was associated with a significant decrease in body weight but not plasma volume in the responders. Indapamide did not change plasma norepinephrine levels, but decreased pressor responsiveness to exogenous norepinephrine. Responders had lower initial plasma renin activity and a smaller absolute increase in plasma renin activity while receiving indapamide, whereas angiotensin II pressor responsiveness was decreased more. The results presented indicate that the blood pressure lowering effect of indapamide in the present patient population is observed with or without renal failure and is associated with a decrease in pressor reactivity. In nonresponders, compensatory mechanisms (e.g., renin) may negate the antihypertensive effect of indapamide.

Cardiovascular System↗

Goniothalamicin and annonacin: bioactive acetogenins from Goniothalamus giganteus (Annonaceae).

Using brine shrimp lethality for activity-directed fractionation, goniothalamicin (I), a new tetrahydroxy-mono-tetrahydrofuran fatty acid gamma-lactone (acetogenin), has been isolated from ethanolic extracts of the stem bark of Goniothalamus giganteus Hook. f., Thomas (Annonaceae). This novel compound was found to be cytotoxic and insecticidal and inhibited the formation of crown gall tumors on potato discs. Annonacin (II), the only other reported mono-tetrahydrofuran acetogenin, was also isolated; the previously reported 9ASK (astrocytoma reversal) activity of II was confirmed, and II is now also found to be weakly active against 3PS murine leukemia.

Animals↗

Angiolymphoid hyperplasia with eosinophilia (Kimura's disease) of the orbit.

A 54-year-old man underwent enucleation of the right eye in 1975 for a malignant melanoma of the choroid, with placement of an Iowa orbital implant. He presented in 1985, with the clinical appearance of a late orbital recurrence of the choroidal malignant melanoma. However, histologic examination revealed the orbital mass to be angiolymphoid hyperplasia with eosinophilia (Kimura's disease). Only six cases of orbital involvement, proved by pathologic studies, have been published in the ophthalmic English literature. This case represented an unusual presentation of a rare disorder that involved the orbit and was probably related to the orbital implant.

Angiolymphoid Hyperplasia with Eosinophilia↗

Identification of disulfide-containing peptides by performic acid oxidation and mass spectrometry.

In addition to reducing the analysis time, the direct examination of proteolytic digests by fast atom bombardment mass spectrometry (FABMS) greatly extends the information that is available from peptide mapping experiments. Mass spectral data are particularly useful for identifying post-translationally modified peptides. For example, the molecular weight of a disulfide-containing peptide may be used to locate the disulfide bond in the protein from which the peptide was derived. This paper describes a new procedure, which is useful for identifying disulfide-bonded peptides. Peptides are treated with performic acid to modify certain residues and thereby cause a characteristic change in the peptide molecular weight. This change in molecular weight is determined by FABMS and used to help identify peptides. Results for a series of small peptides demonstrate that Cys, Met, and Trp are the only residues that undergo a change in molecular weight under the conditions used here. Furthermore, these changes in molecular weight are diagnostic for each of the residues. Cysteinyl-containing peptides are of particular interest, because their identification is essential for locating disulfide bonds. The molecular weight of a peptide increases by 48 mu for each cysteinyl residue present. This approach is used to identify peptides that contain both cysteinyl and cystinyl residues in the peptic digest of bovine insulin. The method is extended to the analysis of a tryptic digest of cyanogen bromide-treated ribonuclease A. A computer-assisted analysis procedure is used to demonstrate the specificity with which peptide molecular weight is related to specific segments of the protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, High Pressure Liquid↗

Acute volume loading, atrial natriuretic peptide release and cardiac function in healthy men. Effects of beta-blockade.

Release of ANP is dependent on right atrial distension and pressure, which in turn are dependent on both venous return and left ventricular function. These two latter parameters are both modulated by beta-receptors. In the present study, the effects of selective beta-blockade vs non-selective beta-blockade on hypertonic volume expansion induced changes in ANP release and systemic hemodynamics were assessed in 8 healthy normotensive male volunteers. On placebo, infusion of hypertonic saline (1200 ml of 2.5% NaCl) caused an intravascular volume expansion of 10-11%, and small non-significant increases in cardiac performance (LVEDV, SV, or CI), but it provoked a 2-fold increase in plasma ANP. Beta-blockade by either atenolol or propranolol blunted the increase in cardiac volume load (reflected by LVEDV) as compared to placebo, but did not affect the ANP response to volume expansion. The increase in ANP correlated closely with the intravascular volume expansion on placebo and to a lesser extent on beta-blockade. In healthy men, therefore, intravascular volume expansion that caused only small changes in cardiac activity, resulted in clear increases in release of ANP. Inhibition of the increase in cardiac volume load by beta-blockade did not interfere with ANP increase, suggesting a role for extra-cardiac receptors in the release of ANP or a change in the pressure/volume relationship.

Adrenergic beta-Antagonists↗

Building the infrastructure for primary health care: an overview of vertical and integrated approaches.

In the past four decades there has been a succession of different approaches to the development of infrastructure for the delivery of health services. There have been striking similarities among these approaches in both direction and timing in many different countries, particularly in the developing world. While the general trend has been strongly in the direction of a more comprehensive, integrated health infrastructure, there have been important regressions from this path. It is suggested that the recent attention given to the delivery of 'selective' packages of interventions has often diverted energy and resources from the essential task of developing comprehensive, efficient and effective health services. This paper begins with an historical review of trends in the development of health services infrastructure in recent decades. It proceeds to analyse the implications for the organization of health services and for resource allocation when the health services infrastructure is viewed as part of a health system based on primary health care. Finally, we maintain that district health systems based on primary health care provide an excellent practical model for health development, including an appropriate health system infrastructure. Within this model the concerns with accelerating the application of known and effective technologies and the concerns with strengthening of community involvement and intersectoral action for health are both accommodated. The district health system provides a realistic setting for dialogue and planning involving both professionals and non-professionals concerned with health and social development.

Developing Countries↗

Properties of fatty acyl-coenzyme A: estradiol-17 beta acyltransferase in bovine placenta microsomes.

The properties of the enzyme catalyzing the formation of non-polar derivatives of estradiol-17 beta (E2) esterified to long-chain fatty acids have been investigated in microsomal preparations from bovine placenta cotyledons. A rapid enzyme assay has been developed which involves simple solvent partitioning. The membrane-bound enzyme showed a pH optimum of 5.0 and addition of fatty acyl-coenzymes A (CoAs), such as oleoyl-CoA, palmitoyl-CoA and palmitoleoyl-CoA, increased [3H]E2-fatty acyl ester formation from [3H]E2 by some 7-fold. Linoleoyl-CoA, linolenoyl-CoA and arachidonoyl-CoA were much less effective as acyl donors. Only 17 beta-fatty acyl monoesters were synthesized in each instance. Similar results were obtained with microsomes or mitochondria from bovine endometrium. The apparent Km for E2 employing placenta microsomes was 8.0 +/- 2.2 (SD) microM. Steroids such as testosterone, dehydroepiandrosterone and 5-androstene-3 beta, 17 beta-diol acted as competitive inhibitors (Ki values 79, 46 and 39 microM, respectively). These, and other data to be reported separately, which showed that these steroids were substrates for the enzyme, demonstrate that the latter is not specific for E2. The [3H]E2-fatty acyl ester fractions biosynthesized from [3H]E2 and bovine placental or endometrial tissue were analyzed by high pressure liquid chromatography (HPLC) and were found to have similar compositions characterized by a high percentage of unsaturated fatty acids.

Acyl Coenzyme A↗

Inhibition of atherosclerosis by fish oil in cholesterol-fed rabbits.

To evaluate the effects of dietary fish oil on cholesterol-induced atherosclerosis, 36 New Zealand rabbits in four groups were fed a 0.3% cholesterol diet for 10 weeks. One group served as control, whereas groups I, II and III received 1, 2 and 3 ml/day, respectively, of fish oil (Protochol, eicosapentaenoic acid, 180 mg, and docosahexaenoic acid [DHA], 120 mg/ml). The percent of aortic and pulmonary atherosclerosis was measured by planimetry of sudanophilic lesions. The percent of aortic lesions in the control group was 59 +/- 22%. The two higher dose fish oil groups showed a significant reduction in aortic lesions: group I (40 +/- 26%, p = NS), group II (18 +/- 11%, p less than 0.01) and group III (36 +/- 22%, p less than 0.05). Area of pulmonary artery lesions was significantly higher in the control group (48 +/- 22%) as compared with group I (15 +/- 13%, p less than 0.01), group II (4 +/- 3%, p less than 0.01) and group III (8 +/- 9%, p less than 0.01). The high cholesterol diet in the control group decreased bleeding time from 82 +/- 17 to 59 +/- 22 s (p less than 0.05). Groups II and III showed an increased bleeding time (62 +/- 15 to 84 +/- 17 s and 66 +/- 22 to 95 +/- 27 s; p less than 0.05, respectively). Fish oil did not significantly alter total serum cholesterol and high density lipoprotein (HDL) cholesterol. In group II triglyceride decreased from 128 +/- 22 to 64 +/- 25 mg/dl (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗