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Biomedical subjects

J O Phillips

Publications and source records attributed to J O Phillips.

At least 37 records · Page 2Linked to original sources
PubMed1996

A prospective study of simplified omeprazole suspension for the prophylaxis of stress-related mucosal damage.

OBJECTIVES: To determine the efficacy, safety, and cost of simplified omeprazole suspension in mechanically ventilated critically ill patients who have at least one additional risk factor for stress-related mucosal damage. DESIGN: Prospective, open-label study. SETTING: Surgical intensive care and burn unit at a university tertiary care center. PATIENTS: Seventy-five adult, mechanically ventilated patients with at least one additional risk factor for stress-related mucosal damage. INTERVENTIONS: Patients received 20 mL of simplified omeprazole suspension (containing 40 mg of omeprazole) initially, followed by a second 20-mL dose 6 to 8 hrs later, then 10 mL (20 mg) daily. Simplified omeprazole suspension was administered through a nasogastric tube, followed by 5 to 10 mL of tap water. The nasogastric tube was clamped for 1 to 2 hrs after each administration. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was clinically significant gastrointestinal bleeding determined by endoscopic evaluation, nasogastric aspirate examination, or heme-positive coffee ground material that did not clear with lavage, which was associated with at least a 5% decrease in hematocrit. Secondary efficacy measures were gastric pH measured 4 hrs after omeprazole was first administered, mean gastric pH after omeprazole was started, and the lowest gastric pH during omeprazole therapy. Safety-related outcomes included the occurrence rate of adverse events and pneumonia. No patient experienced clinically significant upper gastrointestinal bleeding after receiving omeprazole suspension. The 4-hr postomeprazole mean gastric pH was 7.1, the mean gastric pH after starting omeprazole was 6.8, and the mean lowest pH after starting omeprazole was 5.6. The occurrence rate of pneumonia was 12%. No patient in this high-risk population experienced an adverse event or a drug interaction that was attributable to omeprazole. CONCLUSIONS: Simplified omeprazole suspension prevented clinically significant upper gastrointestinal bleeding and maintained gastric pH of > 5.5 in mechanically ventilated critical care patients without producing toxicity.

Adolescent↗
PubMed1996

In vivo gene transfer to the human biliary tract.

The human biliary tract offers an excellent model for gene transfer studies for a variety of diseases localized to the liver. The aim of this study was to determine if a viable liver might be employed to study viral transfection of the human biliary system in order to mimic in vivo human experiments. Using a normal human liver initially procured for transplantation, but subsequently found unsuitable, and with an intact biliary tree, the hepatic vascular supply was accessed for continuous perfusion. The common and left hepatic biliary system was isolated by balloon catheterization. A replication defective adenoviral vector containing the Escherichia coli beta-galactosidase (lac Z) reporter gene (AdCMVLacZ) was injected into the catheter-isolated left and common bile duct lumen. Viral exposure to the right duct system was prevented by ligation. The bile duct segments were excised and prepared for enzymatic (X-gal) staining. Intense staining was observed in the biliary epithelium exposed to the adenoviral vector. No evidence of beta-galactosidase staining was noted in the unexposed biliary mucosa. We report direct transfection of biliary epithelial cells from normal human liver with a recombinant adenovirus. Our data suggest potential therapeutic applications for gene therapy of hepatobiliary disorders.

Adenoviridae↗
PubMed1995

Prospective evaluation of neomycin serum concentrations after direct corpora cavernosa irrigation during penile prosthesis placement.

OBJECTIVES: To determine if toxic serum levels of neomycin are generated after direct corpora cavernosa irrigation during penile prosthesis placement. METHODS: We have used an infection prophylaxis technique that involves directly irrigating the corpora cavernosa tissue (through the corporotomy) with 0.5% neomycin solution. Serum neomycin concentrations were measured at 1 hour and 4 hours after irrigation in 13 patients undergoing penile prosthesis placement. A subset of patients who had preimplant and postimplant serum creatinine concentrations was evaluated for changes in renal function. RESULTS: The mean 1-hour postirrigation serum neomycin level was 1.2 micrograms/mL and the mean 4-hour postirrigation level was 1.2 micrograms/mL. These serum neomycin concentrations are lower than those thought to be necessary to produce nephrotoxicity or ototoxicity. Renal function was not significantly affected by the neomycin irrigation. CONCLUSIONS: Although aminoglycosides are ototoxic and neomycin has the highest nephrotoxic potential of the aminoglycosides, we conclude that direct irrigation of the corpora cavernosa with 0.5% neomycin solution does not produce significant systemic exposure to result in nephrotoxicity or ototoxicity. One-time prophylactic neomycin irrigation remains an effective, safe, and economic adjunct to penile prosthesis placement.

Creatinine↗
PubMed1995

Rapid horizontal gaze movement in the monkey.

1. We studied horizontal eye and head movements in three monkeys that were trained to direct their gaze (eye position in space) toward jumping targets while their heads were both fixed and free to rotate about a vertical axis. We considered all gaze movements that traveled > or = 80% of the distance to the new visual target. 2. The relative contributions and metrics of eye and head movements to the gaze shift varied considerably from animal to animal and even within animals. Head movements could be initiated early or late and could be large or small. The eye movements of some monkeys showed a consistent decrease in velocity as the head accelerated, whereas others did not. Although all gaze shifts were hypometric, they were more hypometric in some monkeys than in others. Nevertheless, certain features of the gaze shift were identifiable in all monkeys. To identify those we analyzed gaze, eye in head position, and head position, and their velocities at three points in time during the gaze shift: 1) when the eye had completed its initial rotation toward the target, 2) when the initial gaze shift had landed, and 3) when the head movement was finished. 3. For small gaze shifts (< 20 degrees) the initial gaze movement consisted entirely of an eye movement because the head did not move. As gaze shifts became larger, the eye movement contribution saturated at approximately 30 degrees and the head movement contributed increasingly to the initial gaze movement. For the largest gaze shifts, the eye usually began counterrolling or remained stable in the orbit before gaze landed. During the interval between eye and gaze end, the head alone carried gaze to completion. Finally, when the head movement landed, it was almost aimed at the target and the eye had returned to within 10 +/- 7 degrees, mean +/- SD, of straight ahead. Between the end of the gaze shift and the end of the head movement, gaze remained stable in space or a small correction saccade occurred. 4. Gaze movements < 20 degrees landed accurately on target whether the head was fixed or free. For larger target movements, both head-free and head-fixed gaze shifts became increasingly hypometric. Head-free gaze shifts were more accurate, on average, but also more variable. This suggests that gaze is controlled in a different way with the head free. For target amplitudes < 60 degrees, head position was hypometric but the error was rather constant at approximately 10 degrees.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Coordination of gaze shifts in primates: brainstem inputs to neck and extraocular motoneuron pools.

To determine whether there are brainstem regions that provide common input to the motoneurons that move both the head and the eyes, we injected wheat germ agglutinin-horseradish peroxidase complex (WGA-HRP) into neck motoneuron pools at spinal level C2 (N = 3) and extraocular motoneuron pools in the abducens (N = 1) and oculomotor/trochlear (N = 1) nuclei of rhesus and fascicularis macaques. We also injected WGA-HRP into spinal level C5-7 (N = 1) of a fascicularis macaque for comparison. After injections into C2, we observed retrogradely labeled cells in the ventral reticular formation (NRV), the gigantocellular reticular formation (NRG), and both the oral (NRPO) and the caudal (NRPC) divisions of the paramedian pontine reticular formation (PPRF). There was also a column of labeled cells in the cuneate reticular nucleus (NCUN) just lateral to the ipsilateral periaqueductal gray (PAG). This column extended rostrally into the central mesencephalic reticular formation (CMRF). In addition, there were labeled cells in the region ventral and caudal to the rostral interstitial nucleus of the MLF (riMLF), the area lateral to the interstitial nucleus of Cajal (INC), and the ventral part of the lateral vestibular nucleus (LVN) and lateral part of the medial vestibular nucleus (MVN). There were also a few labeled cells in the fastigial (FN) and interposed (IN) nuclei of the cerebellum but very few in the superior colliculus (SC). In contrast, the injection into C5-7 labeled many cells in the lateral vestibular nucleus (LVN) and very few in FN or IN. Injecting WGA-HRP into the abducens nucleus and the surrounding tissue labeled many cells in SC, PPRF, MVN, FN, and nucleus prepositus hypoglossi (NPH). Injecting into the oculomotor/trochlear nuclei and nearby tissue labeled cells in SC, INC, riMLF, FN, IN, MVN, and superior vestibular nucleus (SVN). Structures that project to both neck and eye motoneuron pools, and therefore probably participate in both head and eye movements, include the lateral part of the MVN and both NRPO and NRPC in the PPRF. Those that project primarily to neck motoneurons in C2 include the NRV, the NRG, and the NCUN-CMRF column. Those projecting exclusively to extraocular nuclei include the NPH, INC, riMLF, NRPD, and SC. We use these data to propose a scheme for control of combined eye-head movements in monkeys.

Afferent Pathways↗
PubMed1994

Upregulation of secretin receptor gene expression in rat cholangiocytes after bile duct ligation.

Secretion stimulates ductular bile secretion by binding to receptors on intrahepatic bile duct epithelial cells (i.e., cholangiocytes). In the rat, this choleretic effect increases after bile duct ligation (BDL). Although cholangiocyte proliferation induced by BDL contributes to secretin-induced hypercholeresis, the mechanisms modulating these alterations in secretin-induced ductular bile secretion are obscure. Thus we studied the expression of secretin receptor mRNA (SR-mRNA) in purified liver cells from normal and BDL rats. Northern blot analysis and RNase protection assays with mRNA from purified liver cells demonstrated SR-mRNA only in cholangiocytes; moreover, SR gene expression showed a seven- to ninefold increase in individual cholangiocytes from BDL rats compared with controls. This increase in SR-mRNA expression was related to a similar increase in the rate of transcription of SR-mRNA in cholangiocytes from BDL rats. Thus our studies indicate that 1) SR-mRNA is detected in liver only in cholangiocytes; 2) BDL causes an increase in SR-mRNA in individual cholangiocytes; and 3) the increase in SR-mRNA after BDL is partly related to an increase in the rate of transcription of SR-mRNA by cholangiocytes after BDL. Our data suggest that upregulation of the SR gene may contribute to secretin-induced hypercholeresis.

Animals↗
PubMed1994

Recent advances in the isolation of liver cells.

The development of new and refined separation techniques--including FACS, FFE, CFE and isopyknic gradients--has had a profound impact on the ability of investigators to isolate specific cell types from the liver. Although some of these techniques, such as FFE, may be of limited preparative value, they are nonetheless important analytical tools that detect subtle differences among cell subpopulations. The isolation of highly purified preparations of liver cells in large yields requires the use of more conventional purification methods such as CFE and isopyknic centrifugation. Immunological approaches represent a key development for the isolation of specific liver cell types, especially when they are used in combination with other techniques. Excellent, reliable and relatively simple techniques now exist to isolate highly purified preparations of hepatocytes, cholangiocytes, KCs, SCs, FSC, myofibroblasts and pit cells. Additional work is necessary to refine techniques for the isolation of dendritic cells and lymphocytes.

Animals↗
PubMed1990

Synergistic effect of IL-4 and IFN-gamma on the expression of polymeric Ig receptor (secretory component) and IgA binding by human epithelial cells.

The expression of secretory component (SC), the epithelial receptor for polymeric Ig, was enhanced by the addition of human rIFN-gamma or rIL-4, as revealed by the binding of radiolabeled polymeric, J chain-containing IgA or anti-SC antisera to the human colonic adenocarcinoma epithelial cell line HT-29. In combination, these cytokines exhibited a synergistic effect, and the potentiating effect of IL-4 was inhibitable by polyclonal anti-IL-4 antisera. Because the binding of radiolabeled polymeric IgA (pIgA) to HT-29 cells was inhibited by unlabeled pIgA or a polyclonal anti-SC reagent, but not by IgG, monomeric IgA, or Fab alpha fragments, we conclude that the receptor involved in the increased binding of pIgA is indeed SC. These data suggest that the expression of SC on human epithelial cells and the subsequent binding of pIgA (produced in mucosal tissues and glands by subepithelial plasma cells) is regulated by lymphokines such as IL-4 and IFN-gamma that are presumably derived from T cells found in abundant numbers in these tissues. These findings demonstrate a novel pathway of interaction between T cell products and epithelial cells that may result in enhanced translocation of large amounts of locally produced pIgA through epithelial cells into external secretions.

Biological Factors↗
PubMed1988

IgA-mediated clearance and tissue deposition of dinitrophenylated human serum albumin at various DNP:HSA ratios.

Dinitrophenylated human serum albumin (DNP-HSA) with various DNP:HSA ratios was prepared by direct conjugation with dinitrobenzene sulfate or with a caproic acid spacer group (DNP-cap-HSA) using DNP-epsilon-amino-caproic acid N-hydroxy-succinimide ester. The substitution ratio and chemical linkage (presence of a spacer group) were shown to affect the degree of murine anti-DNP antibody binding to antigen, and hence the tissue deposition and efficiency of hepatobiliary transport. DNP-HSA (4.5:1), which poorly binds to IgA anti-DNP antibody, is inefficiently transported into mouse bile. In contrast, 9:1 DNP-cap-HSA readily forms complexes and is more effectively cleared by the hepatobiliary route. The IgA-mediated increase in liver deposition of DNP-cap-HSA (9:1) was found to be associated with an increase in antigen uptake by hepatocytes. In contrast, large complexes formed between DNP-HSA (49:1) and IgA anti-DNP antibody are taken up by nonparenchymal cells of the liver and thus are inefficiently transported into bile. These results suggest that the IgA-mediated uptake by phagocytic cells or hepatocytes of haptenated protein strongly depends on the degree of haptenation.

Animals↗
PubMed1988

Role of hepatocytes in the uptake of IgA and IgA-containing immune complexes in mice.

The role of parenchymal and nonparenchymal mouse liver cells in the uptake of polymeric IgA (pIgA) and pIgA-containing immune complexes (IC) of low mol. wt (less than 1 x 10(6)) was studied. As detected by immunofluorescence and immunoelectron microscopy, pIgA were bound on the surface of isolated hepatocytes. Following the injection of radiolabeled pIgA or pIgA-IC into mice, the total radioactivity recovered from isolated liver cells was preferentially associated with parenchymal cells. The ability to inhibit the transport of pIgA and pIgA-IC by pIgA of an irrelevant specificity suggests that pIgA-IC and pIgA are bound and transported by the same mechanism. These results indicate that mouse hepatocytes are involved in the uptake and hepatobiliary transport of pIgA and pIgA-IC of low mol. wt.

Animals↗
PubMed1987

Functional and structural prerequisites for clinical pharmacy services.

Pharmacy directors and pharmacists in charge of clinical services at 46 medium-sized hospitals were surveyed to identify possible explanations for previously documented inconsistency in the implementation of clinical pharmaceutical services. There were three study objectives: to determine the extent to which basic structural and functional management prerequisites have been implemented at these institutions; to determine whether a relationship exists between the kind and number of clinical services offered and implementation of these prerequisites; and to identify discrepancies between responses of the pharmacy director and the pharmacist in charge of clinical services at the same hospital to the same questions. One hundred hospitals providing clinical pharmaceutical services were randomly selected from a master list of 190 hospitals that had been grouped into nine geographic areas. Of 17 functional and structural prerequisites studied, 4 to 13 of them had been implemented at the hospitals surveyed. Only 24% of the hospitals had implemented the basic functional prerequisites of unit dose drug distribution and decentralized pharmaceutical services. Of nine clinical pharmaceutical services, one to eight were being delivered. A weak correlation between the number of prerequisites implemented and the number of clinical services provided was found. Significant disagreement was found between the directors and their pharmacists about which prerequisites and clinical services were being implemented. This pilot study suggests that pharmacy directors and clinical pharmacists need to assess how effectively basic management prerequisites are being put into practice in the delivery of clinical pharmaceutical services.

Medication Systems, Hospital↗
PubMed1986

Analysis of the hepatobiliary transport of IgA with monoclonal anti-idiotype and anti-allotype antibodies.

The processing and fate of mixed immune complexes is influenced by the antibody isotypes present. The hepatobiliary transport of mixed immune complexes containing the mouse IgA myeloma protein J558 and corresponding monoclonal IgG or IgM anti-J558 idiotype or monoclonal IgG anti-mouse IgA allotype antibodies has been studied. The anti-idiotype or anti-allotype antibodies were radiolabeled and injected into mice with or without mouse polymeric IgA (J558). IgG anti-idiotype antibodies to J558 IgA were selectively transported into bile by J558 IgA. This process occurred with a radiolabeled Fab preparation of the IgG anti-idiotype and was inhibitable with IgA of an irrelevant antigenic specificity. Thus, polymeric IgA influenced the fate of IgA-IgG idiotype-anti-idiotype serum immune complexes. A monoclonal anti-idiotype antibody of the IgM isotype (D8-3) was not selectively transported into bile by itself or as an IgA-IgM complex. A monoclonal IgG antibody (CB5-6) to a mouse allotype determinant in the Fc portion of IgA was not selectively transported into bile. This anti-allotype monoclonal antibody inhibited the hepatobiliary transport of 125I-polymeric J558 IgA and therefore appeared to directly or indirectly block the site in the Fc region of IgA recognized by the hepatic receptor.

Animals↗
PubMed1986

Isolation and molecular weight determination of two immunoglobulin heavy chains in the channel catfish, Ictalurus punctatus.

Channel catfish (Ictalurus punctatus), a teleost fish, were immunized over a 4 month period with 4 intraperitoneal injections of bovine serum albumin (BSA) in Freund's adjuvant. The catfish anti-BSA antibody was purified by affinity chromatography and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). By elution of catfish anti-BSA antibody from BSA-affinity columns with 3.0 M KSCN and subsequent SDS-PAGE, two immunoglobulin heavy chains were demonstrated in the channel catfish. The molecular weights and the relative percentages found of the two immunoglobulin heavy chains were 72,000 (94%) and 56,000 (6%). The molecular weight of the single light chain found was 23,000. Using the 72,000 mol. wt heavy chain and 23,000 mol. wt light chain and including a molecular weight of 15,000 for the J-chain, the molecular weight of the predominant channel catfish tetrameric IgM immunoglobulin molecule was calculated to be 775,000. Using the 56,000 low mol. wt heavy chain, the molecular weight of a second subclass of the channel catfish tetrameric IgM molecule was calculated to be 647,000. After Sephadex G-200 gel filtration, anti-BSA antibody activity was found only in the 14S globulin fraction by indirect hemagglutination testing.

Animals↗
PubMed1985

Carbohydrate-mediated clearance of secretory IgA from the circulation.

Radioiodinated human secretory IgA (sIgA) injected intravenously into mice was rapidly cleared from the circulation by the liver. A portion of the sIgA was transported as an intact molecule into the bile. However, this transport was less efficient than that of human serum polymeric IgA (pIgA). The clearance of sIgA from the circulation was inhibited by prior injection of asialofetuin, suggesting that its uptake is mediated by the hepatic binding protein (HBP) specific for asialoglycoproteins. Mouse pIgA did not inhibit the hepatic clearance of sIgA. Results of in vivo studies were confirmed by in vitro experiments. The binding of 125I-asialoorosomucoid to either the particulate fraction (2000 g pellet of the homogenate) or the plasma membrane fraction of mouse liver was inhibited by sIgA. When polypeptide components of sIgA were used as inhibitors, significant inhibition was obtained with secretory component (SC), while inhibition with light and J-chains was not statistically significant. Examination of the inhibitory activity of IgA1 and IgA2 myeloma proteins and heavy chains isolated from these proteins revealed that binding of polymeric IgA1 and alpha 1 heavy chains can also be mediated by HBP. However, these interactions appear to be of lower avidity than those with SC. The inhibitory activity of human IgA2 and alpha 2 heavy chains was not significant. The involvement of HBP in binding of sIgA was also confirmed by measuring the inhibition of binding of 125I-sIgA. The binding of this protein by the particulate fraction of the mouse liver homogenate was inhibited by asialoglycoproteins and SC while inhibition with IgA1 and alpha 1 heavy chains was not significant. These results suggest that the carbohydrate moieties recognized by HBP reside primarily in the SC portion of sIgA.

Animals↗
PubMed1984

Selective hepatobiliary transport of human polymeric IgA in mice.

Both subclasses of human polymeric IgA (pIgA) were selectively transported from the serum into the bile of mice relative to human IgG or IgM. Removal of human pIgA from serum corresponded to the clearance kinetics shown for murine pIgA. The biliary pIgA was intact as determined by sucrose density gradient ultracentrifugation. This hepatic uptake was specific for the IgA isotype and occurred independently of receptors in the liver specific for glycoproteins that terminate with galactose or mannose moieties. Desialylation of human pIgA resulted in its rapid clearance from serum and subsequent deposition in the liver in a manner similar to most other desialylated serum glycoproteins. The desialylated pIgA present in bile was also an intact molecule; thus the asialoglycoprotein receptor may represent an additional mechanism for the transport of serum pIgA into bile.

Animals↗