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Biomedical subjects

M Chang

Publications and source records attributed to M Chang.

At least 91 records · Page 5Linked to original sources
PubMed1997

Comparison of chromosomal DNA composing timeless in Drosophila melanogaster and D. virilis suggests a new conserved structure for the TIMELESS protein.

Two proteins, TIM and PER, physically interact to control circadian cycles of tim and per transcription in Drosophila melanogaster. In the present study the structure of TIM protein expressed by D. virilis was determined by isolation and sequence analysis of genomic DNA (gDNA) corresponding to the D. virilis tim locus (v tim ). Comparison of v tim and m tim gDNA revealed high conservation of the TIM protein. This contrasts with poor sequence conservation previously observed for the TIM partner protein PER in these species. Inspection of the v tim sequence suggests an alternative structure for most TIM proteins. Sequences forming an intron in a previously characterized D. melanogaster tim cDNA appear to be most often translated to produce a longer TIM protein in both species. The N-terminal sequence of vTIM and sequence analysis of genomic DNA from several strains of D. melanogaster suggest that only one of two possible translation initiation sites found in tim mRNA is sufficient to generate circadian rhythms in D. melanogaster. TIM translation may be affected by multiple AUG codons that appear to have been conserved in sequences composing the 5'-untranslated tim mRNA leader.

Amino Acid Sequence↗
PubMed1997

Anionic- and lipophilic-mediated surface binding inhibitors of human leukocyte elastase.

We report the synthesis of a series of diphenylmethane-based oligomers containing anionic and lipophilic functionalities that are potent inhibitors of human leukocyte elastase (HLE). The enzyme inhibition is regulated by the size of the oligomer, as well as, the number of charges. Lipophilicity is an important element in determining potency and specificity against other basic enzymes. Compounds whose scaffolds contain three phenoxyacetic acid groups and three alkyl ethers are competitive and specific inhibitors of HLE with Ki = 20 nM. The mechanism of action of this class of compounds is believed to involve multidendate interactions with the surface of HLE near the active site which prevents substrate access to the catalytic site.

Benzhydryl Compounds↗
PubMed1997

Wound hypoxia and acidosis limit neutrophil bacterial killing mechanisms.

BACKGROUND: "Respiratory burst" activity, ie, O2- production, is dependent on PO2, temperature, pH, and glucose concentrations within the physiologic range. OBJECTIVES: To determine whether environmental conditions characteristic of wounds may limit human neutrophil respiratory burst metabolism and to clarify the degree to which bactericidal oxidant production depends on local PO2. METHODS: Human blood and wound neutrophils were stimulated with phorbol myristate acetate. Oxygen consumption and superoxide production were measured over a range of 30 to 300 mm Hg PO2, 0 to 40 mmol/L glucose, pH 6.0 to 8.0, and 30 degrees C to 37 degrees C. The apparent Michaelis Menten constant for oxidant production with respect to PO2 was calculated. RESULTS: Oxygen consumption and O2- production were dependent on PO2 throughout the range tested. Half-maximal oxidant production occurred in the range of 45 to 80 mm Hg PO2 and maximal at PO2 higher than 300 mm Hg. These data agree with the highest previous estimates. Oxidant generation was also dependent on pH, temperature, and glucose concentration, but to a lesser extent. CONCLUSIONS: Leukocyte bacterial killing capacity as measured by oxygen consumption and superoxide production are substantially impaired at the low oxygen tensions often found in wounds. Changes in pH, temperature, and glucose concentration have lesser but nonetheless significant consequences. The data provide a plausible mechanism for the vulnerability of some wounds to infection and for the previous finding that increasing oxygen tension at wound sites enhances bactericidal function. Thus, the data serve as a basis for future studies on prevention of wound infection.

Acidosis↗
PubMed1997

Carbamazepine treatment induces the CYP3A4 catalysed sulphoxidation of omeprazole, but has no or less effect on hydroxylation via CYP2C19.

AIMS: Omeprazole has been shown previously to be metabolized by the two cytochrome P450 isoforms CYP2C19 (hydroxylation) and CYP3A4 (sulphoxidation). The objective of this study was to test the inducibility of these enzymes by carbamazepine (CBZ). METHODS: Omeprazole was given as a single oral dose before and after 3 weeks of treatment of five patients with CBZ (400-600 mg daily). RESULTS: Mean area under the plasma concentration vs time curve (AUC) between 0 and 8 h after drug intake, decreased by about 40% for omeprazole and its hydroxy metabolite and increased for its sulphone metabolite, but the changes were not statistically significant. The ratio of the AUCs of omeprazole and its sulphone, used as an index of CYP3A4 activity, decreased in all patients (P = 0.052), while there was no change in the omeprazole/hydroxyomeprazole AUC ratio used as an index for CYP2C19 activity. There was a significant decrease in the mean ratio of the AUC of the hydroxy and sulphone metabolites from 2.58 to 0.93 (P = 0.046) with a mean difference of 1.79 (95% CI: 0.07 to 3.50) showing that the induction was more pronounced for CYP3A4 than for CYP2C19. CONCLUSIONS: CBZ induces CYP3A4, but not, or to a lesser extent, CYP2C19. The induction of the sulphoxidation of omeprazole by CBZ seems to have no major clinical implication.

Adult↗
PubMed1997

Cloning of a Ca(2+)-ATPase gene and the role of cytosolic Ca2+ in the gibberellin-dependent signaling pathway in aleurone cells.

The ultimate goal of this investigation was to identify intermediary steps in the gibberellin (GA)-dependent signaling pathway in rice aleurone cells. By using a differential display approach, a number of putative GA-responsive genes were isolated. One of them, a GA-responsive Ca(2+)-ATPase gene, was identified and partially characterized. A genomic clone and a cDNA clone were isolated and sequenced. The deduced amino acid sequence showed that this protein resembles an endoplasmic reticulum membrane Ca(2+)-ATPase. In a transient assay in rice aleurone cells, expression of the introduced Ca(2+)-ATPase cDNA bypassed the GA requirement for stimulating the expression of a major target gene, the alpha-amylase c gene (Osamy-c). This result suggests that GA-dependent expression of this Ca(2+)-ATPase gene (OsCa-atpase) plays an important role in the GA-dependent signal-transduction pathway. To investigate the possible involvement of other proteins and genes that may affect the intracellular Ca2+ level, compounds which can block different putative steps in the signal-transduction pathway were introduced into rice aleurone cells, and then the level of the OsCa-atpase transcript or the Osamy-c transcript was monitored. In the presence of GA, the rice Ca(2+)-ATPase and the Ca2+ channels appeared to co-regulate the local concentration of cytosolic Ca2+. The release of Ca2+ from the internal stores to the cytoplasm was presumably initiated by inositol-1,4,5-triphosphate which reached a peak level within 25 min after GA induction. As a second messenger, Ca2+ binds to calmodulin (CaM), and the Ca2+/CaM complex regulates the cytosolic Ca2+ by affecting expression of the OsCa-atpase. Finally, a working model is proposed for the GA-dependent signaling pathway in aleurone cells.

Amino Acid Sequence↗
PubMed1997

Cdc73p and Paf1p are found in a novel RNA polymerase II-containing complex distinct from the Srbp-containing holoenzyme.

The products of the yeast CDC73 and PAF1 genes were originally identified as RNA polymerase II-associated proteins. Paf1p is a nuclear protein important for cell growth and transcriptional regulation of a subset of yeast genes. In this study we demonstrate that the product of CDC73 is a nuclear protein that interacts directly with purified RNA polymerase II in vitro. Deletion of CDC73 confers a temperature-sensitive phenotype. Combination of the cdc73 mutation with the more severe paf1 mutation does not result in an enhanced phenotype, indicating that the two proteins may function in the same cellular processes. To determine the relationship between Cdc73p and Paf1p and the recently described holoenzyme form of RNA polymerase II, we created yeast strains containing glutathione S-transferase (GST)-tagged forms of CDC73, PAF1, and TFG2 functionally replacing the chromosomal copies of the genes. Isolation of GST-tagged Cdc73p and Paf1p complexes has revealed a unique form of RNA polymerase II that contains both Cdc73p and Paf1p but lacks the Srbps found in the holoenzyme. The Cdc73p-Paf1p-RNA polymerase II-containing complex also includes Gal11p, and the general initiation factors TFIIB and TFIIF, but lacks TBP, TFIIH, and transcription elongation factor TFIIS as well as the Srbps. The Srbp-containing holoenzyme does not include either Paf1p or Cdc73p, demonstrating that these two forms of RNA polymerase II are distinct. In confirmation of the hypothesis that the two forms coexist in yeast cells, we found that a TFIIF-containing complex isolated via the GST-tagged Tfg2p construct contains both (i) the Srbps and (ii) Cdc73p and Paf1p. The Srbps and Cdc73p-Paf1p therefore appear to define two complexes with partially redundant, essential functions in the yeast cell. Using the technique of differential display, we have identified several genes whose transcripts require Cdc73p and/or Paf1p for normal levels of expression. Our analysis suggests that there are multiple RNA polymerase II-containing complexes involved in the expression of different classes of protein-coding genes.

Amino Acid Sequence↗
PubMed1997

Cloning, expression, and regulation of rabbit cyclooxygenase-2 in renal medullary interstitial cells.

Prostaglandin synthesis requires cyclooxygenase-1 (COX1) or -2 (COX2), which mediate the conversion of arachidonate to prostaglandin H2. COX1 is the predominant constitutive isoform, whereas COX2 expression is typically low. In the present studies we cloned rabbit COX2 and determined its distribution in unstimulated tissues. Screening rabbit eye and uterine libraries yielded two cDNAs containing identical inserts with a 1,812-nucleotide open-reading frame. This encoded a 604-amino acid polypeptide, 90% identical to human, rat, and mouse COX2. Expression of the rabbit COX2 in HEK-293 cells enhanced prostanoid synthesis. Constitutive COX2 mRNA expression was highest in kidney and urinary bladder. COX2 expression was primarily in renal outer medullary interstitial cells with cortical expression in macula densa. In cultured medullary interstitial cells, COX2 mRNA predominated, with little COX1 expression. Interstitial cell COX2 mRNA but not COX1 was induced by phorbol ester and epidermal growth factor but suppressed by dexamethasone. Phorbol ester also upregulated immunoreactive COX2. Constitutive COX2 in these tissues has important implications for side effects of COX2-selective inhibitors.

Amino Acid Sequence↗
PubMed1997

Cimetidine inhibits the induction of long-term potentiation in the dentate gyrus of rats in vivo.

We investigated the effect of cimetidine, a clinically used H2-receptor antagonist, on the induction of long-term potentiation (LTP) in the dentate gyrus of anesthetized rats. Intracerebroventricular injection of cimetidine (50-100 nmol) inhibited the induction of LTP in a dose-dependent manner. The inhibitory effect of cimetidine was not mimicked by other H2-receptor antagonists (ranitidine, famotidine) or the H1-receptor antagonist diphenhydramine or the H3-receptor antagonist thioperamide. These results suggest that cimetidine inhibits hippocampal synaptic plasticity by a novel brain mechanism unrelated to H1, H2 or H3 receptors.

Animals↗
PubMed1997

Effects of Whole Blood Viscosity on Atherogenesis.

There is a high correlation between high whole blood viscosity and the well known risk factors for arterial occlusive disease: hypertension, hyperlipidemia, diabetes, male sex, age, smoking, and obesity. These risk factors increase whole blood viscosity, whereas the preventive factors of arterial occlusive disease such as fish oil, aspirin, alcohol, and exercise probably tend to reduce whole blood viscosity. The protective adaptation theory recently presented by Kensey and Cho1 proposed high whole blood viscosity as one of the major factors that make up the mechanical injury possibly inducing arterial occlusive disease. New diagnostic and prophylactic treatments for arterial occlusive disease are suggested. An accurate, convenient, and cost-effective blood viscometer that can be used in a clinical environment might become a useful diagnostic screening device for patients at risk for arterial occlusive disease, and it would help discover new prophylactic treatments.

Journal Article↗
PubMed1997

Metabolism of the human immunodeficiency virus type 1 reverse transcriptase inhibitor delavirdine in rats.

Delavirdine mesylate (U-90152T) is a highly specific nonnucleoside reverse transcriptase inhibitor currently under development for the treatment of AIDS. The excretion, disposition, and metabolism of delavirdine were investigated in Sprague-Dawley rats after oral administration of [14C]delavirdine mesylate at single doses ranging from 10 to 250 mg/kg and multiple doses ranging from 20 to 250 mg/kg/day. Excretion studies showed that feces was the major route of elimination, delavirdine was well absorbed (>80%) after a 10 mg/kg single dose, and excretion was dose-dependent. The metabolism of delavirdine in the rat was extensive. The following metabolites were identified (% of dose in rats given 10 and 100 mg/kg, respectively): 6'-hydroxy delavirdine (7.1% and 15.6%) and its glucuronide (12.2% and 6.2%) and sulfate (5.5% and 3.2%) conjugates, despyridinyl delavirdine (12.1% and 11.7%) and its conjugate (13.0% and 11.7%), desalkyl delavirdine (16.5% and 13.4%), and its N-sulfamate, 6'- and 4'-sulfate conjugates (2.9% and 3.9%). Cleavage of the amide bond in delavirdine to give N-isopropylpyridinepiperazine and indole carboxylic acid constituted a minor pathway. Degradation of 6'-hydroxy delavirdine generated despyridinyl delavirdine and the pyridine-ring opened MET-14. The metabolic pathway of delavirdine involved N-desalkylation, pyridine ring hydroxylation, pyridine ring cleavage, and amide bond cleavage.

Administration, Oral↗
PubMed1997

Identification of the metabolites of the HIV-1 reverse transcriptase inhibitor delavirdine in monkeys.

Delavirdine mesylate (U-90152T) is a highly specific nonnucleoside HIV-1 reverse transcriptase inhibitor currently under development for the treatment of AIDS. The metabolism of delavirdine was investigated in male and female cynomolgus monkeys after oral administration of [14C-carboxamide]delavirdine mesylate at single doses of 80 mg/kg and multiple doses of 160 to 300 mg/kg/day. Desalkyl delavirdine was the major metabolite in circulation. In urine, desalkyl delavirdine accounted for nearly half of the radioactivity, with despyridinyl delavirdine and conjugates of desalkyl delavirdine accounting for most of the remaining radioactivity. Bile was mostly composed of desalkyl delavirdine and 6'-O-glucuronide delavirdine, with parent drug, 4-O-glucuronide delavirdine, and conjugates of desalkyl delavirdine as significant components. In addition, several minor metabolites were observed in urine and bile of delavirdine treated monkeys. The metabolism of delavirdine in the monkey was extensive and involved N-desalkylation, hydroxylation at the C-4' and C-6' positions of the pyridine ring, hydroxylation at the C-4 position of the indole ring, pyridine ring-cleavage, N-glucuronidation of the indole ring, and amide bond cleavage as determined by MS and/or one-dimensional and two-dimensional NMR spectroscopies. Phase II biotransformations included glucuronidation, sulfation, and beta-N-acetylglucosaminidation. The identification of the N-linked beta-N-acetylglucosamine and 4-O-glucuronide metabolites of delavirdine represents novel biotransformation pathways.

Animals↗
PubMed1997

Metabolism of the HIV-1 reverse transcriptase inhibitor delavirdine in mice.

Delavirdine mesylate (U-90152T) is a highly specific nonnucleoside HIV-1 reverse transcriptase inhibitor currently under development for the treatment of AIDS. The excretion, disposition, brain penetration, and metabolism of delavirdine were investigated in CD-1 mice after oral administration of [14C]delavirdine mesylate at single doses of 10 and/or 250 mg/kg and multiple doses of 200 mg/kg/day. Studies were conducted with 14C-carboxamide and 2-14C-pyridine labels, as well as 13C3-labeled drug to facilitate metabolite identification. Excretion was dose dependent with 57-70% of the radioactivity eliminated in feces and 25-36% in urine. Pharmacokinetic analyses of delavirdine and its N-desisopropyl metabolite (desalkyl delavirdine) in plasma showed that delavirdine was absorbed and metabolized rapidly, that it constituted a minor component in circulation, that its pharmacokinetics were nonlinear, and that its metabolism to desalkyl delavirdine was capacity limited or inhibitable. Delavirdine did not significantly cross the blood-brain barrier; however, its N-isopropylpyridinepiperazine metabolite arising from amide bond cleavage-was present in brain at levels 2- to 3-fold higher than in plasma. The metabolism of delavirdine in the mouse was extensive and involved amide bond cleavage, N-desalkylation, hydroxylation at the C-6' position of the pyridine ring, and pyridine ring-cleavage as determined by MS and/or 1H and 13C NMR spectroscopies. N-desalkylation and amide bond cleavage were the primary metabolic pathways at low drug doses and, as the biotransformation of delavirdine to desalkyl delavirdine reached saturation or inhibition, amide bond cleavage became the predominant pathway at higher doses and after multiple doses.

Animals↗
PubMed1996

Differential mechanisms in the regulation of endogenous levels of thrombopoietin and interleukin-11 during thrombocytopenia: insight into the regulation of platelet production.

The regulation of megakaryocytopoiesis and thrombopoiesis appears to be under the control of an array of hematopoietic growth factors. To determine the relationship of endogenous thrombopoietic cytokine levels and circulating platelet (PLT) counts, we measured the levels of thrombo-poietin (TPO), interleukin-11 (IL-11), and interleukin-6 (IL-6) in patients with significant thrombocytopenia secondary to both marrow hypoplasia and increased PLT destruction. Increased endogenous levels of TPO and IL-11, but not IL-6, were detected in bone marrow transplant patients with thrombocytopenia following myeloablative therapy (BMT/MAT) (TPO: 1,455.5 +/- 87.3 pg/mL, [PLT 39,600 +/- 7,800/microL], P < .001, n = 12; IL-11: 227.9 +/- 35 pg/mL, [PLT 32,900 +/- 57,000/microL], P < .05, n = 19; IL-6: 25.8 +/- 8.4 pg/mL, [PLT 32,800 +/- 5,057/microL], P > .05, n = 4] v normal donors [TPO < 150 pg/mL, n = 8; IL-11 < 50 pg/mL, n = 9; IL-6 < 10 pg/mL, n = 5 [PLT 203,000 +/- 7,500/microL]. There was a significant inverse correlation between endogenous levels of TPO and IL-11, but not IL-6, and PLT counts in the MAT/BMT patients (TPO: r = -0.57, P < .0001, n = 188; IL-11: r = -0.329, P < .0001, n = 249; IL-6: r = -0.1147, P > .05, n = 62). In patients with immune thrombocytopenia purpura (ITP), with decreased PLT survival, but intact bone marrow megakaryocytopoiesis, endogenous IL-11 levels were significantly increased (328.0 +/- 92.6 pg/mL, [PLT: 20,900 +/- 3,000/microL], P < .05, n = 25). However, endogenous TPO levels remained undetectable (< 150 pg/mL, [PLT 30,500 +/- 5,500/microL], n = 15). These results suggest that there may be differential mechanisms regulating endogenous TPO, IL-11, and IL-6 levels during acute thrombocytopenia and suggest that the absolute number of circulating PLTs may not always be the sole regulator of endogenous TPO levels. Other mpl-expressing cells of the megakaryocyte lineage may contribute to the regulation of circulating TPO levels as well. Our results also suggest IL-11 levels may in part, be regulated by a negative feedback loop based on circulating PLT counts, but also may, in part, be regulated by a variety of inflammatory agonists. Both TPO and IL-11, therefore, appear to be active thrombopoietic cytokines regulating, in part, megakaryocytopoiesis during states of acute thrombocytopenia.

Adolescent↗
PubMed1996

A role for an inhibitory connexin in testis?

Functional expression of gap junction proteins can be obtained conveniently with the paired oocyte cell--cell channel assay. So far all gap junction proteins (connexins), with the exception of one, have been found to make functional channels either by themselves or as hybrid channels (two hemichannels of different connexin composition). Connexin33 (cx33) appears not to follow this rule. Expression of cx33 in oocytes does not yield functional channels, and attempts to identify another connexin with which cx33 can form hybrid channels have failed so far. The observation was made that cx33 inhibits functional expression of other connexins in a connexin-specific way. While expression of cx32 remains unaffected by coinjection into oocytes of cx33 mRNA together with cx32 mRNA, junctional conductance obtained with cx43 is marginally reduced whereas coinjection of cx33 mRNA at equimolar concentrations almost completely abolishes functional cx37 expression. The fact that testis is the only tissue found to express significant levels of cx33 mRNA together with cx37 and cx43 suggests a possible functional role for an inhibitory connexin. A model is proposed where cx33 limits a cell's capability to make functional channels by allowing formation of heterotypic channels with other cells while formation of homotypic channels is disallowed. Such a mechanism would permit asynchronous maturation of germ cells while at the same time allowing communication between germ cells and Sertoli cells.

Animals↗
PubMed1996

Retinal degeneration in transgenic mice with photoreceptor-specific expression of a dominant-negative fibroblast growth factor receptor.

Mutant cDNAs coding for dominant-negative forms of the fibroblast growth factor receptors 1 (FGFR-1) and 2 (FGFR-2) that lack tyrosine kinase activity were ligated to a 2.2 kb DNA fragment containing the bovine rhodopsin promoter and used to generate transgenic mice. Six independent lines were generated with the FGFR-1 construct, and five were generated with the FGFR-2 construct. Five of the six FGFR-1 mutant lines and all five FGFR-2 mutant lines showed transgene expression in the retina by reverse transcription-PCR. By both in situ hybridization and immunohistochemistry, mutant FGFRs were found to be expressed specifically in photoreceptors of transgene-positive FGFR-1 and FGFR-2 mice. Lines expressing the FGFR-2 mutant showed progressive photoreceptor degeneration; the retinas showed minimal or no abnormalities at 1 month, but by 2 months they showed focal areas of thinning of the outer nuclear layer and disruption of photoreceptors. By 2-4 months, areas of complete loss of photoreceptors were seen. These abnormalities were not seen in control littermates not expressing the transgene. Mice from two FGFR-1 mutant lines showed focal areas of thinning of the outer nuclear layer and numerous photoreceptors with fragmented chromatin, whereas the other FGFR-1 lines showed minimal or no abnormalities. These data indicate that perturbation of FGF signaling in photoreceptors is associated with progressive photoreceptor degeneration, suggesting that one or more of the FGFs may act as a survival factor for photoreceptor cells.

Animals↗
PubMed1996

Endogenous interleukin-11 (IL-11) expression is increased and prophylactic use of exogenous IL-11 enhances platelet recovery and improves survival during thrombocytopenia associated with experimental group B streptococcal sepsis in neonatal rats.

Future preventive and/or concurrent therapy of neonatal sepsis may require the use of adjuvant immunohematopoietic therapy. In the present study, using reverse transcription-polymerase chain reaction, we demonstrated a significant increase in IL-11 mRNA extracted from the femurs of group B streptococcus (GBS)-infected rats during acute thrombocytopenia (platelet count: 65.8 +/- 19.3 K/mm3, n = 5) compared to that of uninfected neonatal rats (NR) (635.2 +/- 89 K/mm3, n = 5) (174 +/- 17% vs. 100%, p < 0.001, n = 5). We next investigated the prophylactic effect of rhIL-11 on the PLT recovery as well as survival in NR during experimental GBS sepsis. NR received either rhIL-11 (250 micrograms/kg/d) intraperitoneally for 11 d or sham injections before the induction of experimental GBS sepsis. While experimental GBS sepsis resulted in severe thrombocytopenia in control NR, the rhIL-11 pre-treated group had significantly higher PLT counts (24 hr: 417 +/- 50 vs. 221 +/- 54 K/mm3, p < 0.01; 36 hr: 276 +/- 60 vs. 82 +/- 33 K/mm3, p < 0.01; 48 hr: 402 +/- 77 vs. 101 +/- 82 K/mm3, p < 0.05). Administration of rhIL-11 alone also significantly increased the survival rate at 36 and 48 hrs after GBS inoculation compared to the control group (36 hr: 83% vs. 58%, p < 0.05; 48 hr: 50% vs. 18%, p < 0.01, n > or = 30), as did the combination of rhIL-11 with ABS treatment at 36 hrs, compared to the control group (90% vs. 69%, p < 0.05, n > or = 30). These results suggest that endogenous IL-11 gene expression may be upregulated during acute thrombocytopenia and associated bacterial sepsis in NR. This increase in IL-11 gene expression, however, does not appear to prevent severe thrombocytopenia. Furthermore, prophylactic administration of pharmacological doses of rhIL-11 may be potentially beneficial in the management of neonatal GBS sepsis and its associated thrombocytopenia. Future studies are needed to determine the clinical implications of these findings.

Animals↗
PubMed1996

Effect of syringe size on bruising following subcutaneous heparin injection.

BACKGROUND: Bruising and induration associated with subcutaneous heparin injection often result in sustained tenderness and severe ecchymosis at the injection site. Research-based practice guidelines for subcutaneous heparin administration are needed to reduce these adverse effects. OBJECTIVES: The purpose of this study was to investigate the effect of syringe size (1-mL vs 3-mL) on postinjection-site bruising and induration following the administration of subcutaneous heparin. METHODS: A convenience sample of 29 subjects receiving 5000 units of subcutaneous heparin at least twice a day was recruited from a large urban hospital. Subjects received their regularly scheduled subcutaneous heparin injections with a 3-mL or a 1-mL syringe in a randomized sequence using a standardized procedure. Injection sites were assessed for bruises and induration at 24, 48, and 72 hours after injection. RESULTS: The incidence of injection site bruising with 1- and 3-mL syringes was 79% and 69%, respectively. The use of a 3-mL vs 1-mL syringe resulted in significantly smaller bruises at 48 and 72 hours after injection. Induration at the injection site occurred in three patients. CONCLUSIONS: Findings suggest that 3-mL syringes are preferable to 1-mL syringes for heparin administration. The effect of other injection-related variables should be studied with the use of the 3-mL syringe, and tested on various populations.

Adult↗