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Biomedical subjects

A L Adams

Publications and source records attributed to A L Adams.

At least 19 recordsLinked to original sources

Effects of whole cottonseed diet and recombinant bovine somatotropin on ovarian follicles in lactating dairy cows.

The effects of whole cottonseed (WCS) in the diet and the administration of bovine somatotropin (bST) on ovarian follicular dynamics and plasma progesterone (P4) concentrations were examined in cows during a period of synchronized follicular growth. Lactating Holstein cows (n = 28) were randomly assigned to treatments in a 2 x 2 factorial arrangement. Diets consisted of WCS (15% of dry matter) or no WCS, and bST at a dose of 0 or 208 mg/14 d. Dietary treatments began within 24 h of calving and bST treatments began within 7 d postpartum. Cows received GnRH at 65 +/- 3 d postpartum (d 0), PGF2alpha, (d 7), a second dose of GnRH (d 9), and were inseminated 16 h later (d 10). Ovarian changes were monitored daily by ultrasonography from d 0 to 9. On d 9,93% of cows had a preovulatory follicle and 86% ovulated. For Class 2 (6 to 9 mm) follicles, a diet x bST interaction was detected, with bST stimulating Class 2 follicles in cows fed WCS, but not in cows on the control diet. Neither diet nor bST affected numbers of Class 1 (2 to 5 mm) or Class 3 (> or = 10 mm) follicles or sizes of the subordinate and dominant follicles. During the luteal phase of the cycle, lactating cows fed WCS tended to have elevated concentrations of plasma P4, whereas bST was without effect. Plasma concentrations of high-density lipoprotein cholesterol were increased in cows fed WCS. Number and diameter of corpora lutea did not differ among treatments.

Animal Feed↗

Effects of gossypol from cottonseed on hematological responses and plasma alpha-tocopherol concentration of dairy cows.

The effects of feeding whole cottonseed (WCS) and bovine somatotropin (bST) administration on hematological responses and plasma alpha-tocopherol concentrations of lactating dairy cattle were examined. After parturition, multi and primiparous Holstein cows (n = 159) were assigned randomly to a 2 x 2 factorial arrangement of treatments consisting of (0 or 15% WCS and 0 or 208 mg of bST injected every 2 wk starting within 7 d after calving. Blood samples were collected from a subset group of 64 cows at 14, 28, 42, and 56 d postpartum. Blood was collected from all cows (n = 159) at 75, 96 and 120 d postpartum. Blood samples were analyzed for alpha-tocopherol and total and (+)- and (-)-gossypol in plasma. Erythrocyte osmotic fragility, hemoglobin and hematocrit also were determined in blood. The mean concentrations of alpha-Tocopherol, total, and (+)- and (-)-gossypol were higher in cows fed WCS regardless of bST administration and plateaued by d 75 postpartum. Hematocrit and hemoglobin concentrations were not affected by treatments. Erythrocyte osmotic fragility was higher in cows fed WCS, but the increase was attenuated when bST was injected (diet x bST interaction). No clinical signs of gossypol toxicity were observed in the cows consuming the WCS.

Animals↗

Phase I trial of multiple cycles of high-dose carboplatin, paclitaxel, and topotecan with peripheral-blood stem-cell support as front-line therapy.

PURPOSE: To determine the safety and feasibility of delivering multiple cycles of front-line high-dose carboplatin, paclitaxel, and topotecan with peripheral-blood stem-cell (PBSC) support. PATIENTS AND METHODS: Patients were required to have a malignant solid tumor for which they had received no prior chemotherapy. Mobilization of PBSC was achieved with either filgrastim alone or in combination with cyclophosphamide and paclitaxel. Patients then received three or four cycles of high-dose carboplatin (area under the concentration-time curve [AUC] 16), paclitaxel (250 mg/m(2)), and topotecan (10-15 mg/m(2)), with the latter two agents administered as 24-hour infusions and supported with PBSC and filgrastim. Cycles were repeated every 28 days. RESULTS: Twenty patients were enrolled onto the trial and were assessable for toxicity and clinical outcome. Dose-limiting toxicities were stomatitis and prolonged hematopoietic recovery. The maximum-tolerated dose of topotecan was 12.5 mg/m(2) when given with high-dose carboplatin and paclitaxel for three cycles. Four cycles were able to be given with a dose of topotecan of 10 mg/m(2). The pharmacokinetics of each compound were not affected by the other agents. Eleven (85%) of 13 patients with assessable disease responded. CONCLUSION: Multiple cycles of high-dose carboplatin, paclitaxel, and topotecan can be safely administered with filgrastim and PBSC support. The recommended doses for phase II study are carboplatin AUC 16, paclitaxel 250 mg/m(2), and topotecan 10 mg/m(2). Trials are currently being conducted with this regimen as front-line treatment in patients with advanced ovarian cancer and extensive small-cell carcinoma. This approach remains experimental and should be used only in the context of a clinical trial.

Adult↗

Targeted delivery of a peripheral benzodiazepine receptor ligand-gemcitabine conjugate to brain tumors in a xenograft model.

PURPOSE: Peripheral benzodiazepine receptors (PBRs) are overexpressed in brain tumors compared to normal brain, and could serve as a target to selectively increase anticancer drug delivery through a PBR ligand-drug conjugate system. We have previously synthesized PBR ligand-gemcitabine conjugates based on the model PBR ligand, PK11195. The goal of the current study was to examine this new drug delivery strategy in an intracerebral xenograft model by measurement of steady-state drug distribution following administration of gemcitabine (GEM) and PK11195-GEM. METHODS: In vitro PBR receptor binding and cytotoxicity assays were used to screen three different PK11195-GEM conjugates (GG01, GG02, GG03) in human SF126 glioma cells. Based on these findings and the favorable chemical stability of GG01, here referred as PK11195-GEM, pharmacokinetic investigations of PK11195-GEM and GEM were conducted in male rats. These studies consisted of single-dose and steady-state dosing regimen studies, the latter to assess drug distribution in normal brain and brain tumors. PK11195-GEM and GEM were measured in blood and tissue samples by HPLC. RESULTS: All PBR-GEM conjugates demonstrated appreciable receptor binding affinity and cytotoxicity with mean IC50 values ranging from 248 to 376 nM and 5.6 to 29.1 nM, respectively. The cytotoxicity of GEM was comparable with a mean IC50 value of 5.9 nM. Following administration of single 8 mg/kg doses of PK11195-GEM to rats (n=4), PK11195-GEM had a mean total clearance of 126.3 +/- 29.6 ml/min per kg, and a volume of distribution at steady-state of 1,261.9 +/- 31.05 ml/kg that resulted in a very short elimination half-life of 16.1 +/- 5.8 min. In comparison GEM had a similar volume of distribution (993.8 +/- 131.6 ml/kg), reduced clearance (3.4 +/- 0.8 ml/ min per kg), and longer half-life (235.6 +/- 26.7 min). In nude rats bearing intracerebral tumors, mean steady-state tumor/plasma, tumor/right brain, and tumor/left brain PK 11195-GEM concentration ratios were 1.75 +/- 0.46, 5.49 +/- 5.2, and 9.96 +/- 3.2, respectively. The analogous values following GEM administrations were 0.81 0.5, 3.67 1.57, and 5.21 +/- 1.95, respectively. These values indicate a minimum twofold increase in tumor target selectivity for the conjugate delivery system compared to GEM treatment. CONCLUSION: Targeting intracellular PBRs is a new drug delivery strategy based on the use of low molecular weight drug conjugates that can be administered systemically. It was demonstrated under steady-state conditions that PK11195-GEM possessed a twofold enhancement in brain tumor selectivity compared to GEM alone. This type of target selectivity would allow higher tumor concentrations to be achieved in conjunction with lower drug concentrations in normal or non-target tissues.

Animals↗

Pleural amyloidosis mimicking mesothelioma: a clinicopathologic study of two cases.

Two cases of pleural amyloidosis are presented. The patients are two men, 70 and 72 years of age respectively. Neither patient had evidence of systemic amyloidosis. Each presented clinically with symptoms of chest pain and dyspnea. Radiologically, both patients showed diffuse pleural thickening similar to that observed in malignant mesothelioma. In both patients, surgical decortication of the pleura was performed. Histologically, the lesions were characterized by the presence of an amorphous eosinophilic material with focal collections of a lymphoplasmacytic infiltrate. Focal clusters of giant cells were admixed with the lymphoplasmacytic infiltrate. Histochemical stains for Congo red showed strong positive apple-green birefringency. Immunohistochemical studies using kappa and lambda light chains showed polyclonality. The cases discussed herein represent an unusual presentation of amyloid and one that needs to be considered in the differential diagnosis of malignant mesothelioma.

Aged↗

Analysis and simulation of a stochastic, discrete-individual model of STD transmission with partnership concurrency.

Deterministic differential equation models indicate that partnership concurrency and non-homogeneous mixing patterns play an important role in the spread of sexually transmitted infections. Stochastic discrete-individual simulation studies arrive at similar conclusions, but from a very different modeling perspective. This paper presents a stochastic discrete-individual infection model that helps to unify these two approaches to infection modeling. The model allows for both partnership concurrency, as well as the infection, recovery, and reinfection of an individual from repeated contact with a partner, as occurs with many mucosal infections. The simplest form of the model is a network-valued Markov chain, where the network's nodes are individuals and arcs represent partnerships. Connections between the differential equation and discrete-individual approaches are constructed with large-population limits that approximate endemic levels and equilibrium probability distributions that describe partnership concurrency. A more general form of the discrete-individual model that allows for semi-Markovian dynamics and heterogeneous contact patterns is implemented in simulation software. Analytical and simulation results indicate that the basic reproduction number R(0) increases when reinfection is possible, and the epidemic rate of rise and endemic levels are not related by 1-1/R(0), when partnerships are not point-time processes.

Computer Simulation↗

Modeling contact networks and infection transmission in geographic and social space using GERMS.

BACKGROUND: Stochastic models of discrete individuals and deterministic models of continuous populations may give different answers to questions about infectious diseases. GOAL: Discrete individual model formulations are sought that extend deterministic models of infection transmission systems so that both model forms contribute cooperatively to model-based decision making. STUDY DESIGN: GERMS models are defined as stochastic processes in continuous time with parameters analogous to those in deterministic models. A GERMS model simulator was developed that insured that the rate of events depended only on the current state of model. RESULTS: The confidence intervals of long-term averages of infection level in simulated GERMS models were shown to contain the deterministic model means. CONCLUSION: GERMS models provide a convenient framework for testing the sensitivity of model-based decisions to a variety of unrealistic assumptions that are characteristic of differential equation models. GERMS especially facilitates making more realistic assumptions about contact patterns in geographic and social space.

Humans↗

The role of early HIV infection in the spread of HIV through populations.

The combination of two factors gives early HIV infection an especially strong influence on transmission dynamics: (a) increased transmission probabilities and (b) increased transmission potential of partners infected during this period. Most attention has been focused on the first factor because it fits the way we usually think about risk factors affecting individuals. The second factor acts not on individuals, but across chains of transmission. It is missed by models with constant partnership formation rates over an individual's life or with random mixing. It cannot be assessed from available data collected from individuals. Its assessment requires data from both individuals in a partnership. We demonstrate that this second effect can be so strong that early infection can dominate transmission dynamics even when transmission probabilities are only modestly increased. This second effect is not directly parameterized in our models but arises from two realistic types of temporal variation in partnership formation: (a) Partnership formation rates vary by age with preferential partnership formation in one's own age group, and (b) individuals of any age can experience transient periods of high-risk partnership formation. In a model with only the age-related effect, early infection is observed to dominate transmission dynamics when 20% of transmissible virus is allocated to the first 6 weeks of infection, 7% to middle infection, and 73% to late infection. This domination occurs both early in the course of an epidemic and later when endemic infection levels have been reached. When the second effect is added, early infection is seen to dominate transmission in a model allocating 10% of transmissible virus to the first 6 months, 40% to middle infection, and 50% to late infection. In this model, transmission probabilities during early infection are only 4.17 times those of middle infection and half those of late-stage infection.

Age Factors↗

Effects of varying forage types on milk production responses to whole cottonseed, tallow, and yeast.

Four forage treatments (45% corn silage, 33.75% corn silage plus 11.25% alfalfa hay, 11.25% bermudagrass hay, or 11.25% cottonseed hulls on a DM basis) were arranged factorially with no added fat, 12.5% whole cottonseed, or 2.5% tallow. Different diets were fed during three 28-d periods to 20 control Holstein cows and to 20 cows receiving yeast continuously in a split-plot design. Milk yield of cows fed cottonseed hulls with corn silage was 2.4 kg/d higher than with corn silage plus bermudagrass hay and .7 kg/d higher than with corn silage only or corn silage plus alfalfa hay. Whole cottonseed depressed milk yield by 1 kg/d. Cows fed yeast had increased DMI, and yeast interacted with forage so that more milk was produced by cows fed alfalfa diets. Yeast depressed milk protein percentage. Holstein cows in a commercial Florida dairy were fed no yeast or 10 g/d continuously for 60 d; milk fat percentage was greater (3.51 vs. 3.37%) with yeast. In summary, effects on milk and SCM were positive when cottonseed hulls were utilized with corn silage, negative with whole cottonseed, and neutral with supplemental tallow. Yeast effects on SCM, although not significant for either experiment, tended to be positive for both (mean +1.2 kg/d per cow).

Animal Feed↗

Operative cholangiography.

The value of operative cholangiography in the management of biliary tract disease has been questioned. To better define the role of cholangiography, we reviewed 579 consecutive cholecystectomies done by 1 group of surgeons in a small rural practice over 8 years. Cholangiography demonstrated unsuspected common bile duct disease in 5% of the procedures, while 12% of the patients were spared an unnecessary choledochotomy after a normal cholangiogram was obtained. There was no morbidity, mortality, or prolongation of the hospital stay attributed to the cholangiographic procedure. These findings bolster the argument for routine cholangiography as a safe, effective, and helpful screening examination for patients who are at risk for having common bile duct disease.

Adolescent↗

Rapid identification of proteins on flat surfaces, using antibody-coated metal oxide suspensions.

Suspensions of Fe3O4 (black), Fe2O3 (red), and Cr2O3 (green) were exposed to solutions of protein A, and then each to a different antiserum to one of the following human proteins: fibrinogen, high molecular weight kininogen (HMK), albumin or immunoglobulins (IgG). Test surfaces were patterns of human proteins adsorbed out of solutions or out of plasma, onto glass as well as onto polyvinylchloride slides. They were exposed to single or mixed suspensions of the treated oxides for about 30 s and rinsed. Adhesion of each oxide onto each matching protein of these patterned test surfaces resulted, thus identifying each protein by color.

Antibodies↗

Lack of exchange among plasma proteins in narrow spaces on glass, demonstrated with metal oxide coatings.

Onto 'activating' surfaces, intact normal plasma deposits an overlapping sequence of proteins, each being desorbed by the next. Ultimately, high molecular weight kininogen (HMK) is deposited unless contact was too short, or space between 2 surfaces too narrow. Thus, injected between a glass slide and a convex lens, intact plasma will leave a disk of HMK with a center of fibrinogen. We describe here how the exchange of proteins on the surface can be demonstrated by staining the adsorbate with a metal oxide suspension. Subsequent flooding of the preparation with more normal plasma causes lift-off of the oxide where underlying fibrinogen is being displaced by the HMK of the newly applied plasma. Kininogen-deficient plasma fails to remove any oxide, while normal plasma can remove nearly all of the oxide and adsorbate, left on glass by HMK-deficient plasma.

Adsorption↗

The effect of high molecular weight kininogen on surface-adsorbed fibrinogen.

High molecular weight kininogen (HMWK) plays an important role in altering the association of plasma fibrinogen with surfaces. Plasma initially deposits fibrinogen onto most materials, but on hydrophilic surfaces within 10 min adsorbed plasma fibrinogen cannot be detected on the surface by anti-fibrinogen antisera. However, using HMWK-deficient plasma, fibrinogen remains immunologically identifiable. The interrelationship of adsorbed plasma fibrinogen with kininogen on hydrophilic surfaces is studied further using glass slides stained for protein with Coomassie Blue, and oxidized silicon crystal slices in an automated ellipsometer. On glass slides when plasma that is deficient in both low molecular weight kininogen (LMWK) and HMWK, is reconstituted with HMWK (0.04 Units/ml), fibrinogen is no longer detected on the surface. This finding is specific for HMWK, since, when the same plasma is reconstituted with LMWK (220 micrograms/ml), the amount of fibrinogen detected on the surface is unchanged. The alteration of surface-adsorbed fibrinogen by HMWK is not due to plasmin-induced fibrinolysis, since it occurs in plasminogen-free plasma. In the ellipsometer, surface adsorption of normal plasma is associated with a significantly less (p less than 0.0005) thick protein layer (1.99 +/- 0.08 degree change in azimuth) than plasmas deficient in HMWK (2.32 +/- 0.11). Using ellipsometry, HMWK in plasma is shown to shorten the time in which immunologically detectable surface-adsorbed fibrinogen was removed or altered. These studies in a whole plasma system present further evidence that HMWK specifically modifies the association of plasma fibrinogen with hydrophilic surfaces.

Adsorption↗

Tongue extrusion as an aid to blind nasal intubation.

Blind nasal intubation often results in esophageal placement of the tube because reflex swallowing and supralaryngeal structures direct the tube posteriorly. Extrusion of the tongue, which inhibits swallowing and shifts the supralaryngeal structures anteriorly, facilitated blind placement of a nasotracheal tube in 14 of 16 critically ill patients. The technique avoids manipulation of the neck, the use of heavy sedation or anesthesia, and requires no specialized training or equipment.

Adult↗

Interaction of high molecular weight kininogen, factor XII, and fibrinogen in plasma at interfaces.

Using ellipsometry, anodized tantalum interference color, and Coomassie blue staining in conjunction with immunologic identification of proteins adsorbed at interfaces, we have previously found that fibrinogen is the main constituent deposited by plasma onto many man-made surfaces. However, the fibrinogen deposited from normal plasma onto glass and similar wettable materials is rapidly modified during contact activation until it can no longer be identified antigenically. In earlier publications, we have called this modification of the fibrinogen layer "conversion," to indicate a process of unknown nature. Conversion of adsorbed fibrinogen by the plasma was not accompanied by marked change in film thickness, so that we presumed that this fibrinogen was not covered but replaced by other protein. Conversion is now showen to be markedly delayed in plasma lacking high molecular weight kininogen, slightly delayed in plasma lacking factor XII, and normal in plasma that lack factor XI or prekallikrein. We conclude that intact plasma will quickly replace the fibrinogen it has deposited on glass-like surfaces by high molecular weight kininogen and, to a smaller extent, by factor XII. Platelets adhere preferentially to fibrinogen-coated surfaces; human platelets adhere to hydrophobic nonactivating surfaces, since on these, adsorbed firbinogen is not exchanged by the plasma. The adsorbed fibrinogen will be replaced on glass-like surfaces during surface activation of clotting, and platelets failing to find fibrinogen will not adhere.

Adsorption↗