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B J Ransil

Publications and source records attributed to B J Ransil.

At least 37 records · Page 2Linked to original sources
PubMed1995

The effects of hyaluronidase on local anesthesia: a prospective, randomized, controlled, double-blind study.

Hyaluronidase, an enzyme that breaks down intercellular cement, has been advocated as an additive to local anesthetics because it allows injected solutions to spread and penetrate tissues. Because epinephrine is commonly used in conjunction with local anesthetics, the combined effects of both hyaluronidase and epinephrine were studied in a prospective, controlled, double-blind manner. The forearms of volunteers ranging in number from 15 to 23 were injected with 0.5 ml of lidocaine to which graded doses of hyaluronidase and epinephrine had been added. At various intervals after injection, the areas of anesthesia were measured. From these data, the time to reach peak area of anesthesia (onset), the size of the peak area of anesthesia, and the time until disappearance of anesthesia (duration) were computed and analyzed. We found that epinephrine has a more profound effect on the onset, area, and duration of anesthesia than hyaluronidase. Epinephrine delayed the time to reach peak area of anesthesia (onset) relative to lidocaine alone more than hyaluronidase (0.28 h versus 0.04 h). When both agents were used together, the effect was subtractive (0.28-0.04 = 0.24 h, compared with 0.22 h observed). This suggests a negative interaction (inhibition) because hyaluronidase decreased the epinephrine effect by 21 percent. Concerning the size of peak area of anesthesia, epinephrine increased the area relative to lidocaine alone more than hyaluronidase (626 versus 221 mm2). When both agents were used together, the effect was additive (626 + 221 = 847 mm2, compared with 848 mm2 observed). This suggests that the two agents acted independently of each other in relation to area of anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

A review of scrotal violation in testicular cancer: is adjuvant local therapy necessary?

High inguinal orchiectomy is the standard initial treatment for suspected testicular carcinoma. Nonstandard surgical approaches (scrotal violations), including scrotal orchiectomy, open testicular biopsy and fine needle aspiration, have historically been condemned as significantly compromising patient prognosis. Patients with scrotal violation are often subjected to potentially morbid or disfiguring local therapies. In addition, patients with scrotal violations are usually disqualified from surveillance protocols. A review was conducted of all published series of testicular cancer patients in whom scrotal violation occurred. A meta-analysis was then performed to choose a subset for critical analysis on the effect of scrotal violation on patient prognosis. Of 1,182 cases included in the final analysis scrotal violation occurred in 206. The rates for local recurrence, distant recurrence and survival were analyzed separately for all patients, patients with stage I disease and patients with pure seminoma or nonseminomatous germ cell tumor. Additionally, the effect of local treatment for scrotal violation on prognosis was examined. Although statistically significant differences were found in the local recurrence rate among the scrotal violation and inguinal group studies, the overall local recurrence rates were small (2.9% versus 0.4%, respectively). There were no statistical differences in distant recurrence or survival rates in all groups analyzed. Patients with scrotal violation who did not receive any local therapy fared as well as those who did receive local therapy. Although the standard treatment of primary testicular cancer remains high inguinal orchiectomy, these data suggest that scrotal violation does not impart a significantly worse overall prognosis. These data would also indicate that patients with stage I disease and scrotal violation should not necessarily be disqualified from surveillance protocols or subjected to adjuvant local therapy.

Humans↗
PubMed1994

Effect of hypnotic suggestion on the delayed-type hypersensitivity response.

OBJECTIVE: To determine whether individuals selected for good general health, high hypnotizability, and the ability to alter skin temperature under hypnotic suggestion can influence the delayed-type hypersensitivity (DTH) response to varicella-zoster (VZ) antigen under hypnotic suggestion. DESIGN: A blinded clinical trial using a repeated measures design with subjects serving as their own controls. Subjects were randomly assigned to undergo a predetermined sequence of four different experimental conditions, occurring at weekly intervals, with each condition including VZ skin testing: (1) hypnosis with suggestions to enhance the DTH response to VZ antigen; (2) hypnosis with suggestions to suppress the DTH response; (3) hypnosis with suggestions for relaxation only; and (4) skin testing without hypnosis. SETTING: A National Institutes of Health-supported clinical research center in a teaching hospital. SUBJECTS: A stratified sample of 24 ambulatory, healthy, highly hypnotizable, volunteer college students selected for their above-average ability to alter skin temperature after hypnotic suggestions and their positive baseline responses to VZ antigen. There were 11 males and 13 females with a mean +/- SD age of 22 +/- 6 years. The mean +/- SD hypnotizability score (Harvard Group Scale of Hypnotic Susceptibility) was 11 +/- 1. INTERVENTIONS: Intradermal skin testing with VZ antigen (Mantoux method) and hypnotic suggestion. MAIN OUTCOME MEASURES: Areas of induration of the DTH response measured at 24 and 48 hours after injection of antigen. RESULTS: The area of the DTH response was not affected by the experimental interventions. The area of erythema was likewise unaffected. CONCLUSIONS: Our subjects were unable to alter their DTH responses using hypnotic suggestion.

Adult↗
PubMed1994

Factors associated with back pain after childbirth.

BACKGROUND: Back pain after childbirth is a frequent complaint. The purpose of this study was to determine the incidence of back pain 1-2 months post partum and to identify the factors, including epidural anesthesia for labor and delivery, that may predispose to it. METHODS: Women delivering a viable singleton infant were interviewed 12-48 h after delivery for a history of back pain that occurred before, during, or both before and during the recent pregnancy and for details of their delivery experience. Two months later, the women interviewed were sent a follow-up questionnaire regarding the occurrence of back pain 1-2 months post partum. RESULTS: Follow-up data were available for 1,042 (88%) of the 1,185 women originally interviewed. The incidence of post partum back pain in women who received epidural anesthesia was equivalent to those who did not (44% vs. 45%). Through stepwise multiple logistic regression, post partum back pain was found to be associated with a history of back pain, younger age, and greater weight. However, new-onset post partum back pain was found to be associated with greater weight and shorter stature. No statistically significant association was found between post partum back pain and epidural anesthesia, number of attempts at epidural placement, duration of second stage of labor, mode of delivery, or birth weight. CONCLUSIONS: The overall incidence of back pain 1-2 months post partum in this population was 44%. Predisposing factors were a history of back pain, younger age, and greater weight. Predisposing factors for new-onset post partum back pain were greater weight and shorter stature. Epidural anesthesia for labor and delivery did not appear to be associated with back pain 1-2 months post partum.

Adult↗
PubMed1994

Immunopathogenic events in acute infection of rhesus monkeys with simian immunodeficiency virus of macaques.

Infection of the rhesus monkey with simian immunodeficiency virus of macaques (SIVmax) was employed to explore the early immune events associated with the initial containment of an acute AIDS virus infection. In nine rhesus monkeys infected intravenously with uncloned SIVmac strain 251, high-level p27 plasma antigenemia was usually detected transiently from approximately day 7 through day 21 following virus inoculation. SIVmac replication in lymph nodes measured by in situ RNA hybridization closely paralleled the time course and magnitude of viremia. The containment of SIVmac spread by 3 to 4 weeks following infection suggests an efficient, early immune control of this virus infection. Anti-SIVmac antibodies were first detected in the blood at approximately day 14. At the time antigenemia was decreased or cleared, SIVmac neutralizing antibodies were present. A rise in circulating and lymph node CD8+ T cells also occurred coincident with the clearance of antigenemia and persisted thereafter. These CD8+ lymphocytes in lymph nodes had increased expression of both major histocompatibility complex class II and the adhesion molecule LFA-1; they also demonstrated decreased expression of the naive T-cell-associated CD45RA molecule. SIVmac-specific cytotoxic T-lymphocyte precursors were detected in both blood and lymph node by 7 days post-virus inoculation. These studies indicate that both virus-specific humoral and cellular immune mechanisms in blood and lymph node are associated with the clearance of viremia that occurs within the first month of infection of rhesus monkeys with SIVmac.

Animals↗
PubMed1994

Test-retest reliability of the Edinburgh Handedness Inventory and Global Handedness preference measurements, and their correlation.

Test-retest reliability of the Edinburgh Handedness Inventory and of self-reported Global Handedness (left, right, ambidextrous), administered 18 mo. apart, was evaluated for 735 adult subjects. Conventional methods for evaluating test-retest reliability were compared with cross-tabulation and the kappa statistic, using as criteria both the degree of agreement and the degree and direction of disagreement. Inventory-derived laterality scores were correlated with Global Handedness responses, yielding a characteristic distribution of laterality scores for each global response which permitted the partitioning of the J-shaped frequency distribution plot of laterality scores into right, left, and ambidextrous regions. Test-retest reliability of the correlation between global responses and laterality scores on retest was demonstrated.

Adult↗
PubMed1993

Deconjugation of bilirubin-IX alpha glucuronides: a physiologic role of hepatic microsomal beta-glucuronidase.

beta-Glucuronidase is an acid hydrolase located in both the lysosomal and microsomal compartments of the hepatocyte. The function of the latter remains undefined. We postulated that microsomal beta-glucuronidase may be responsible for the deconjugation of bilirubin-IX alpha glucuronides which are synthesized primarily in the hepatic microsomal compartment. We utilized two unique congenic strains of mice to characterize the role of hepatic beta-glucuronidase in the metabolism and disposition of bilirubin-IX alpha; the first exhibited less than 1% of total hepatic beta-glucuronidase activity (ATM), the second lacked only the microsomal enzyme activity (AT1). The biliary excretion of bilirubin-IX alpha conjugates was quantitated using reverse-phase high performance liquid chromatography. Under basal conditions, there was a 2-fold increase in the biliary excretion of bilirubin-IX alpha monoglucuronides and total glucuronides in the AT1 and ATM mutants compared to the normal controls. When the plasma bilirubin-IX alpha level was increased to approximately 7 mg/dl to simulate hyperbilirubinemia, by intravenous administration of [14C]bilirubin-IX alpha, mathematical modeling of the biliary excretion curves of bilirubin-IX alpha glucuronides revealed qualitative differences between control and mutant animals, whereas both mutant groups were similar. Collectively, these data demonstrate that microsomal beta-glucuronidase modulates the net rate of bilirubin-IX alpha glucuronidation and glucuronide excretion in bile, under both basal and hyperbilirubinemic conditions, and that lysosomal beta-glucuronidase has no such effects. Hepatic microsomal beta-glucuronidase appears likely to influence the biliary excretion and hence the hepatic elimination of endogenous and xenobiotic substrates (e.g. carcinogens) which undergo hepatic glucuronidation.

Animals↗
PubMed1993

Relationship of abnormal intracellular calcium mobilisation to myocyte hypertrophy in human ventricular myocardium.

OBJECTIVE: Calcium transients in muscles from patients with end stage heart failure consist of two components (L1 and L2) at physiological extracellular calcium concentrations ([Ca2+]o); the second component (L2) can appear in normal human myocardium at high [Ca2+]o. In muscles from end stage heart failure patients L2 is associated with significant hypertrophy. To expand these observations a group of muscles from control patients with mild hypertrophy but without overt heart disease was studied (n = 8), in which a second calcium transient component was present during high [Ca2+]o. METHODS: Using the ratio of the two components of the calcium transient (L2/L1) seen in trabeculae from heart failure patients as a marker of intracellular calcium mobilisation, the hypothesis was tested that the extent of abnormality in transsarcolemmal calcium flux, and/or sarcoplasmic reticular calcium release and reuptake, correlates with the degree of hypertrophy present. RESULTS: In contrast to non-hypertrophied myocardium, hypertrophied myocardium from patients without heart failure often showed an increase in the L2/L1 ratio at higher [Ca2+]o. Hypertrophied myocardium from patients with failure showed a progressive increase in the L2/L1 ratio, reflecting further impairment of calcium mobilisation. There was a positive correlation between the degree of hypertrophy and calcium mobilisation alterations that was enhanced by raised [Ca2+]o. Altered [Ca2+]i mobilisation may develop early in the course of hypertrophy, before the onset of clinical signs of cardiac dysfunction.

Aequorin↗
PubMed1993

Cellular mechanism of the positive inotropic effect of hydralazine in mammalian myocardium.

1. The purpose of this study was to elucidate the cellular mechanism of the positive inotropic effect of hydralazine, a vasodilator widely used for afterload reduction in patients with heart failure that has also been reported to have positive inotropic effects on the heart. After isolation, right ventricular papillary muscles from the ferret were maintained in bicarbonate-buffered salt solution (30 degrees C). A concentration-response relationship was obtained for hydralazine (10(-6) to 10(-3) M). In order to mimic different levels of catecholamine release found in heart failure, we utilized two methods of stimulation: (a) threshold punctate pulses and (b) suprathreshold punctate stimulation with voltage approximately 10% above threshold. 2. In a first group of muscles (n = 16), a maximally effective concentration of hydralazine (10(-3) M) increased peak isometric tension by 39 +/- 9% (P < 0.05). Doses lower than 10(-5) M had no significant effect. The bioluminescent Ca2+ indicator, aequorin, was loaded into a subset of these muscles (n = 7). A significant increase in peak light (i.e., intracellular Ca2+) developed, concurrently with an increase in peak tension (38 +/- 5% to 66 +/- 8%). This inotropic response was associated with a decrease in time to peak tension (ms), 221 +/- 7 to 186 +/- 5 (P < 0.05), and time to peak light, 65 +/- 4 to 52 +/- 2 (P < 0.05). These effects were markedly attenuated by pretreatment with autonomic blocking agents. 3. In a second group of muscles (n = 12), histamine was used to stimulate cyclic AMP production in the presence of propranolol. Hydralazine (3 x 10-4 M) led to a shift in the pD2 (i.e. the negative log of the concentration of histamine producing 50% of the maximal response) from 6.1 +/- 0.1 to 5.9 +/- 0.1(P <0.05), thus increasing the sensitivity of the muscles to histamine. Hydralazine also increased maximum tension from 160 +/- 77% to 195 +/- 57% (P <0.05) above baseline. Thus, hydralazine altered the potency and efficacy of histamine despite the presence of beta-adrenoceptor blockade.4. A third group of muscles were chemically skinned to examine the effects of hydralazine on myofilament Ca2+ responsiveness. Pretreatment of ferret papillary muscles with hydralazine (10-3 M)before skinning did not shift the force-pCa curve after skinning (n = 16). However, hydralazine added to previously skinned fibres desensitized the myofilaments, as indicated by a rightward shift of the force-pCa curve (n = 12). Maximum tension development was not changed.5. The pharmacological effects of hydralazine are characteristic of inotropic drugs that act mainly via cyclic AMP; however, the increase in peak tension demonstrated with histamine in the presence of hydralazine also suggests an effect on cyclic AMP-independent second messenger pathways. These data are consistent with reports that large doses of hydralazine may increase cellular levels of cyclic AMP, as well as other second messengers, by direct cardiac and indirect neuronal mechanisms.

Actin Cytoskeleton↗
PubMed1993

Comparative evaluation of clinically available inferior vena cava filters with an in vitro physiologic simulation of the vena cava.

PURPOSE: A physiologic in vitro model of the human inferior vena cava (IVC) was developed to evaluate the clot-trapping efficiency of various IVC filters. MATERIALS AND METHODS: The flow model closely simulates the physical parameters of the human IVC in fluid viscosity, specific gravity, temperature, and pulsatility; blood flow velocity, volume, and inherent turbulence; and vein orientation, wall compliance, and clot composition. Five filters--Greenfield (G), Bird's Nest (BN), Vena Tech (VT), Simon nitinol (SN), and titanium Greenfield (TG)--were compared by using two vena cava and blood clot sizes and horizontal and vertical orientation of the model. RESULTS: Each filter varied significantly in its clot-capturing efficiency, depending on vena cava size and orientation and emboli size. Overall, decreasing rank order in filter clot-trapping efficiency was SN, BN, VT, TG, and G. CONCLUSION: The in vitro model of the human IVC is an alternative to multicenter clinical trials in evaluating the relative clot-trapping efficiency of various IVC filters.

Equipment Design↗
PubMed1993

Ligand-binding properties of the two isoforms of the human insulin receptor.

Tissue-specific alternative splicing of exon 11 of the insulin receptor gene results in 2 mRNAs that differ by 36 nucleotides within the coding region. The 2 transcripts encode 2 protein isoforms with (Ex11+) or without (Ex11-) 12 additional amino acids at the carboxy-terminus of the receptor alpha-subunit. Previous studies of the 2 isoforms of the human insulin receptor expressed in mammalian cell transfectants have revealed small functional differences at the levels of equilibrium insulin binding affinity and acute ligand-induced receptor internalization. In the present study, we determined the biochemical basis for differential insulin binding affinity. Further functional characterization of the 2 receptor isoforms was also performed. The results obtained were as follows. 1) Studies of ligand association demonstrated a faster (1.8-fold) "on rate" for Ex11- receptors than for Ex11+ receptors, as determined by the kinetics of [125I]insulin binding to transfected cells. In addition, dissociation of prebound [125I]insulin from Ex11- receptors was characterized by an accelerated "off rate" relative to that of Ex11+ receptors. 2) Using both intact Chinese hamster ovary (CHO) cells and partially purified solubilized insulin receptors, the ability of insulin-like growth factor-I to compete for [125I]insulin binding to either isoform differed markedly. The mean IC50 for Ex11- was 40 nM vs. 350 nM for Ex11+. 3) Both Ex11- and Ex11+ receptors were equally capable of hybrid formation with endogenous CHO cell insulin-like growth factor-I receptors. 4) The relative abilities of 2 inhibitory polyclonal antiinsulin receptor antisera to displace [125I]insulin binding did not differ between the two isoforms. 5) Studies of insulin-induced (300 nM) receptor down-regulation in CHO cell transfectants suggested preferential down-regulation of Ex11- receptors; however, no down-regulation difference was observed when Rat 1 cell transfectants expressing the two splice variants were studied. These findings further support the idea that the 2 isoforms of the insulin receptor are functionally distinct in important ways.

Animals↗
PubMed1992

Hepatic microsomal bilirubin UDP-glucuronosyltransferase. The kinetics of bilirubin mono- and diglucuronide synthesis.

Hepatic biotransformation of bilirubin to the hydrophilic species bilirubin mono- (BMG) and diglucuronide (BDG) by microsomal bilirubin UDP-glucuronosyl-transferase (GT) is a prerequisite for its physiologic excretion into bile. The reaction mechanism of bilirubin-GT and the access of bilirubin and BMG (the intermediate substrate) to the active site of bilirubin-GT are undefined. Highly purified [14C]bilirubin and [3H] BMG were coincubated with rat liver microsomes, and the initial rates of radiolabeled bilirubin glucuronide synthesis were measured. Although these substrates differ markedly in their hydrophilicity, no significant differences were observed in [14C]- and [3H]BDG rates of formation from equimolar [14C]bilirubin and [3H] BMG, in the absence or presence of soluble binding proteins (albumin and hepatic cytosol). In further kinetic studies, [14C]bilirubin and [3H]BMG exhibited mutually competitive inhibition of [3H]- and [14C]BDG synthesis, respectively, and [3H]BMG also inhibited [14C]BMG formation. Finally, unlabeled BMG and BDG inhibited the glucuronidation of [14C]bilirubin, with all three pigments yielding virtual Michaelis-Menten dissociation constants in the 10-20 microM range. These findings indicate that: 1) bilirubin-GT follows Michaelis-Menten kinetics for both bilirubin and BMG glucuronidation over the range of substrate concentrations employed; 2) the findings are consistent with a single active site for the enzymatic synthesis of both BMG and BDG; 3) bilirubin, BMG, and BDG bind competitively to this active site with comparable affinities; and 4) access of both bilirubin and BMG substrates to the enzymatic active site is reduced by soluble binding proteins.

Animals↗
PubMed1992

Cyclosporine nephropathy: morphometric analysis of the medullary thick ascending limb.

The effects of cyclosporine A (CsA) (12.5 mg/kg/d) on the medullary thick ascending limb (mTAL) were studied in five experimental groups: vehicle-treated control (C), salt depletion (SD), cyclosporine (CsA), and the combination of both salt depletion and cyclosporine for 3 (CsA-SD:S) and 8 (CsA-SD:L) weeks. Evaluation was performed on 1-micron plastic horizontal sections. mTALs were classified as either atrophic or nonatrophic by assessing mitochondrial density. The mean cross-sectional area of atrophic mTALs was found to be significantly smaller than the mean of nonatrophic mTALs in all treatment groups. The percentage of atrophic tubules was found to be significantly increased in both CsA-SD groups as compared with the other three treatment groups (P less than 0.01). Regression analysis indicated a rectangular hyperbolic relationship between the percentage of atrophic tubules and mean nonatrophic tubule cross-sectional area (P less than 0.0001). Thus, low levels of injury are associated with a rapid increase in cross-sectional tubular area (hypertrophy), and this response plateaued with increasing degrees of injury. Terminal plasma creatinine correlated with nonatrophic tubular cross-section area (r = 0.52, P less than 0.003). These studies indicate that CsA induces mTAL atrophy, which is more extensive with salt depletion. With limited injury, hypertrophy develops. However, the hypertrophic response cannot be sustained with increasing degrees of injury. The phenomenon of mTAL atrophy and hypertrophy is particularly important, since hypertrophy itself is a known risk factor for mTAL injury.

Animals↗
PubMed1992

Cellular basis of negative inotropic effect of 2,3-butanedione monoxime in human myocardium.

2,3-Butanedione monoxime (BDM) exerts a marked negative inotropic effect and has been shown to have protective actions on human myocardial force production that may be of clinical use. To determine the underlying mechanisms, we studied the effects of BDM on chemically skinned and aequorin-loaded myopathic human myocardium from transplant recipients. Eighteen muscles were chemically skinned with saponin (250 micrograms/ml) and then subjected to activation-relaxation cycles, with and without 5 mM BDM. Contracture force vs. Ca2+ data were fitted to a modified Hill equation, and values for 50% maximal activation (pCa50) and maximal Ca(2+)-activated force (Fmax) were obtained. pCa50 was decreased by 0.2 pCa units, indicating myofilament Ca2+ desensitization, and Fmax was reduced by 48% in 5 mM BDM. A second group of intact muscles (n = 8) was loaded with aequorin to monitor intracellular calcium (Cai2+) transients (peak light) and twitch force in the presence of BDM (1-30 mM). Over a range of 1-20 mM, BDM depressed peak light by 3-49% while force was depressed by 10-82%. This was accompanied by an abbreviation of the duration of the twitch but not of the Cai2+ transient. At a concentration of 30 mM, BDM completely inhibited force generation, but an Cai2+ transient was still present. We conclude that in human myocardium, 5 mM BDM predominantly affects cross-bridge force production and Ca2+ sensitivity and has a less pronounced effect on Cai2+.

Aequorin↗
PubMed1992

The inhibitory effects of müllerian-inhibiting substance on epidermal growth factor induced proliferation and progesterone production of human granulosa-luteal cells.

This study was undertaken to determine if Müllerian-inhibiting substance (MIS) could block basal and/or epidermal growth factor (EGF)-induced proliferation and progesterone production by cultured human granulosa-luteal cells. Cells from follicles of individual patients were pooled, counted, and aliquoted into Ham's F-10 medium containing 10% MIS-free female fetal calf serum at 37 C in 95% air and 5% CO2. After assessing viability, cells were counted on days 4, 8, 12, and 16 of culture. EGF was added every other day at 0.2, 2, and 20 ng/mL beginning on culture day 4. The greatest stimulatory effect of EGF on cell proliferation was observed at 20 ng/mL on days 12 and 16. EGF increased progesterone production per cell after 4 days exposure, but this effect was lost after 8 days. Granulosa-luteal cells were cultured with 0.2, 2, and 20 ng/mL immunoaffinity purified recombinant human MIS (rhMIS) or conditioned medium from Chinese hamster ovary cells transfected with the human MIS gene, beginning on culture day 4. rhMIS demonstrated its greatest inhibitory effect on cell proliferation at 20 ng/mL on day 16. The rhMIS decreased progesterone production per cell after 4 days exposure, but only in the higher doses. Maintaining EGF at 20 ng/mL and varying rhMIS yielded significant reduction in EGF-mediated proliferation and progesterone production per cell at 2 and 20 ng/mL rhMIS. These experiments demonstrate rhMIS inhibits basal and EGF-stimulated human granulosa-luteal cell proliferation and progesterone production.

Adult↗
PubMed1991

The effect of epinephrine on blood loss during suction lipectomy.

In a prospective, double-blind, controlled study on 26 consecutive patients who underwent suction lipectomy, the injection of epinephrine (1:250,000, 1:500,000, or 1:1,000,000) was not found to decrease fluid/blood loss when compared with saline injection or no injection at all. Since our study fails to support the use of epinephrine to lessen fluid/blood loss during suction lipectomy, we have abandoned its use in that procedure.

Adult↗