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R F Johnson

Publications and source records attributed to R F Johnson.

At least 37 records · Page 2Linked to original sources
PubMed1999

Transfer of lidocaine across the dual perfused human placental cotyledon.

Factors affecting lidocaine transfer across the normal term human placenta were studied using the dual perfused isolated single cotyledon. Experiments were performed using perfusates which provided equal protein binding in both the maternal and fetal circuits as well as perfusates that approached the actual in vivo maternal/fetal protein binding gradient. Additional experiments were performed to investigate the effects of increasing maternal lidocaine concentration (5, 10, 40, 80 microg/mL) on maternal to fetal (M-->F) lidocaine transfer across the human placenta. Lidocaine crossed the placenta rapidly in both the M-->F and fetal to maternal (F-->M) directions. When protein binding was similar in the two circuits, M-->F transfer ratios (lidocaine transfer/antipyrine transfer) were significantly lower than the transfer ratios seen in the F-->M direction (0.59+/-0.04 versus 0.84+/-0.06, P<0.05). Transfer ratios (M-->F: 0.83+/-0.06, F-->M: 0.96+/-0.06) were not reduced when the physiological maternal/fetal protein binding gradient was present. Lidocaine transfer was not diminished by increasing maternal concentrations and, in contrast to bupivacaine, was not significantly affected by its binding.

Journal Article↗
PubMed1999

A comparison of the placental transfer of ropivacaine versus bupivacaine.

UNLABELLED: This study compares the placental transfer of ropivacaine and bupivacaine using the dual perfused, single cotyledon human placental model. We studied the effects of maternal/fetal protein binding, maternal ropivacaine concentration, and fetal pH on ropivacaine transfer. At a clinically relevant maternal concentration (1 microg/mL), the calculated transfer ratios (local anesthetic percent transfer/antipyrine percent transfer) of ropivacaine (0.82 +/- 0.03) and bupivacaine (0.74 +/- 0.01) were comparable at the completion of the perfusion experiment (120 min). When the perfusates were modified to simulate actual in vivo plasma protein binding values, the maternal-to-fetal transfer of ropivacaine and bupivacaine decreased significantly (P < 0.05) as indicated by transfer ratios of 0.42% +/- 0.07% and 0.40% +/- 0.03%, respectively. No saturation of the transfer process was observed for either drug at the maternal concentrations investigated. The placental transfer of both local anesthetic agents increased significantly as the fetal pH decreased. This investigation shows that ropivacaine and bupivacaine cross the human placenta at a similar rate, despite their differences in lipophilicity and stereochemistry. Placental transfer of both compounds is highly influenced by maternal and fetal protein concentration and the fetal pH. IMPLICATIONS: The placental transfer of ropivacaine was shown to be similar to that of bupivacaine, and is thus highly influenced by the degree of maternal and fetal protein binding and fetal pH.

Adult↗
PubMed1998

Replication-deficient adenovirus vector transfer of gfp reporter gene into supraoptic nucleus and subfornical organ neurons.

The present studies used defined cells of the subfornical organ (SFO) and supraoptic nuclei (SON) as model systems to demonstrate the efficacy of replication-deficient adenovirus (Ad) encoding green fluorescent protein (GFP) for gene transfer. The studies investigated the effects of both direct transfection of the SON and indirect transfection (i.e., via retrograde transport) of SFO neurons. The SON of rats were injected with Ad (2 x 10(6) pfu) and sacrificed 1-7 days later for cell culture of the SON and of the SFO. In the SON, GFP fluorescence was visualized in both neuronal and nonneuronal cells while only neurons in the SFO expressed GFP. Successful in vitro transfection of cultured cells from the SON and SFO was also achieved with Ad (2 x 10(6) to 2 x 10(8) pfu). The expression of GFP in in vitro transfected cells was higher in nonneuronal (approximately 28% in SON and SFO) than neuronal (approximately 4% in SON and 10% in SFO) cells. The expression of GFP was time and viral concentration related. No apparent alterations in cellular morphology of transfected cells were detected and electrophysiological characterization of transfected cells was similar between GFP-expressing and nonexpressing neurons. We conclude that (1) GFP is an effective marker for gene transfer in living SON and SFO cells, (2) Ad infects both neuronal and nonneuronal cells, (3) Ad is taken up by axonal projections from the SON and retrogradely transported to the SFO where it is expressed at detectable levels, and (4) Ad does not adversely affect neuronal viability. These results demonstrate the feasibility of using adenoviral vectors to deliver genes to the SFO-SON axis.

Adenoviridae↗
PubMed1997

Airway simulation to guide stent placement for tracheobronchial obstruction in lung cancer.

BACKGROUND: To effectively palliate large airway obstruction in advanced unresectable lung cancer (stage IIIB or IV), we developed an airway imaging technique to guide selective endobronchial metallic stent placement. METHODS: Fourteen consecutive patients with severe dyspnea (American Thoracic Society grade 4) had a combination of fiberoptic bronchoscopy, chest roentgenography, computed tomographic scanning, helical computed tomography with three-dimensional reconstruction, and intraluminal bronchography with selective bronchial guidewire placement under fluoroscopy to visually reconstruct and simulate the abnormal airway before and during stent placement. Wallstent or Gianturco intraluminal stents were used alone or in combination (up to five stents) to establish patency of the distal trachea and the major bronchi. RESULTS: All 14 patients had successful deployment with initial relief of airway stenosis (>75% predicted diameter). No procedural complications were noted. However, technical problems included stent foreshortening and imprecision of placement, misinterpretation of bronchography (mucous versus tumor), and airway maintenance during manipulation. Length of stay attributable to the procedure averaged 4 days. Stent placement initially improved the dyspnea score in 7 of 14 patients. Five of 14 died in less than 1 month, with the remainder alive at up to 8 months' follow-up. Of those surviving more than 1 month, the Karnofsky score improved in 4 and was unchanged in 5, with 2 dependent (Karnofsky score <50), 3 functional (Karnofsky score, 50 to 70), and 4 active (Karnofsky score >70). CONCLUSIONS: A protocol combining helical computed tomography with three-dimensional reconstruction, bronchography, and bronchoscopy allows accurate assessment of malignant airway obstruction to facilitate intralumenal stent placement for relief of stenosis. Patient selection to favor effective palliation and cost effectiveness has yet to be defined.

Adult↗
PubMed1997

What predicts gastroenterologists' and surgeons' diagnosis and management of common bile duct stones?

BACKGROUND: Because the literature suggests numerous indicators of common bile duct stones, we undertook a systematic assessment of physicians' judgments of the clinical utility of eight indicators: patient age, history of jaundice, history of pancreatitis, levels of serum alanine aminotransferase, alkaline phosphatase, amylase, and total bilirubin, and common bile duct diameter on ultrasonography. METHODS: Random samples of 1500 gastroenterologists and 1500 surgeons were sent a survey asking them to indicate the importance of each potential indicator of common bile duct stones, the likelihood of common bile duct stones for each of nine clinical vignettes, and whether they would order a preoperative ERCP. An abbreviated survey was sent to nonrespondents. RESULTS: Although there was substantial variation in the importances assigned to each indicator, the most important indicators were serum total bilirubin and diameter of common bile duct on ultrasound. The best predictors of the decision to order an ERCP were perceived likelihood of stones and specialty. The average threshold for ordering an ERCP was 37%. Respondents did not differ from nonrespondents in the perceived importance of the eight indicators. CONCLUSIONS: The substantial variation among gastroenterologists and surgeons regarding the optimal approach to common bile duct stones has clinical implications. Patients will receive varying recommendations for care, depending on whom they see.

Adult↗
PubMed1997

The pharmacokinetics of epidural lidocaine and bupivacaine during cesarean section.

We studied the maternal pharmacokinetics of epidural lidocaine and bupivacaine in 20 healthy parturients with institutional review board approval and written, informed consent. Epidural anesthesia was induced using either 2% lidocaine with epinephrine 1:200,000, n = 10, or 0.5% plain bupivacaine, n = 10. Maternal arterial (Ma) blood was sampled at regular intervals and umbilical venous (Uv) blood at delivery. Results for lidocaine and bupivacaine, respectively, were (mean +/- SEM): age 30.4 +/- 1.5 and 24.7 +/- 1.6 yr; weight 74.0 +/- 4.2 and 74.9 +/- 4.5 kg; duration of surgery 55.5 +/- 4.3 and 53.1 +/- 3.5 min; epidural dosage 6.1 +/- 0.6 and 1.5 +/- 0.2 mg/kg; elimination half-life 113.9 +/- 5.6 and 110.4 +/- 20.4 min; plasma clearance 6.1 +/- 0.4 and 13.6 +/- 1.3 mL.kg-1.min-1; volume of distribution 0.98 +/- 0.1 and 1.67 +/- 0.3 L/kg; time to peak concentration 31 +/- 2.3 and 40.5 +/- 1.7 min; peak Ma concentration 6.4 +/- 0.65 and 0.8 +/- 0.1 microgram/mL; and Uv/Ma gradient 0.43 +/- 0.05 and 0.26 +/- 0.1. Peak Ma lidocaine concentrations in 2 of 10 patients reached potentially toxic levels without producing clinical toxicity, whereas peak bupivacaine Ma concentrations never approached levels considered unsafe. The results suggest that epidural bupivacaine reliably produces acceptable Ma concentrations below the toxic range.

Adolescent↗
PubMed1997

The placental transfer of sufentanil: effects of fetal pH, protein binding, and sufentanil concentration.

This study investigated factors that influence the placental transfer of sufentanil using the dual-perfused, single-cotyledon human placental model. Placentas were collected from healthy women. Experiments were designed to elucidate the effects of maternal protein binding, changing maternal sufentanil concentration (1, 10, 20, and 100 ng/mL) and decreasing fetal pH (fetal acidemia 7.2, 7.0, 6.8) on the placental transfer of sufentanil. Sufentanil crossed the placenta rapidly at a rate two-thirds that of the transfer marker, antipyrine. Sufentanil transfer increased linearly with the maternal concentration (r = 0.999). Sufentanil/antipyrine maternal to fetal (M-->F) transfer ratios were significantly reduced (0.66 +/- 0.05 vs 0.40 +/- 0.04, P < 0.05) when fresh frozen plasma was added to the maternal circuit to enhance protein binding. Fetal pH and sufentanil transfer were related because sufentanil M-->F clearance increased significantly as the fetal pH decreased (r = 0.973, P < 0.05). Sufentanil appears to cross the placenta by passive diffusion but is modulated by the degree of maternal protein binding. Sufentanil M-->F transfer is enhanced by fetal acidemia.

Adult↗
PubMed1997

The interaction of meal-related, rhythmic and homeostatic mechanisms and the generation of thirst and drinking.

One of the primary goals of the study of thirst is to understand why drinking occurs under ad libitum or natural conditions. An appreciation of the experimental strategies applied by physiologists studying thirst from different perspectives can facilitate progress toward understanding the natural history of drinking behavior. Drinking research carried out using three separate perspectives-homeostatic, circadian rhythms, and food-associated-generates types of information about the mechanisms underlying drinking behavior. By combining research strategies and methods derived from each of these approaches, it has been possible to gain new information that increases our appreciation of the interactions between homeostatic mechanisms and circadian rhythms in the modulation of water intake and how these might be related to drinking associated with food intake under near natural conditions.

Animals↗
PubMed1997

Dual messenger function for prostaglandin E2 (PGE2) in human placenta.

There is periparturitional increase of prostaglandin E2 (PGE2) in the plasma and amniotic fluid of humans. PGE2 increases uterine contractions and also increases uterine blood flow to sustain the contractions. A question arises as to what role PGE2 plays in human placental circulation. It may regulate feto-placental blood flow and closure of placental resistance vessels at parturition. Therefore, we have investigated (a) the release of PGE2 into fetal and maternal circulations, and (b) the influence of PGE2 on the feto-placental pressure in the isolated perfused cotyledon of normal human term placenta. The placental cotyledon was perfused with aerated. (21% O2, 5% CO2) Krebs-Ringer bicarbonate buffer (pH 7.4, 37 degrees C) containing 2% albumin on both maternal (230 ml, 12 ml/min., 0.6" Hg) and fetal (93 ml, 1.75 ml/min., 1.75" Hg) sides in a closed recirculating system. In one group of cotyledons, perfusion samples (2 ml) were collected at regular intervals from both perfusates for 3 hrs. and PGE2 was determined in aliquots (0.5 ml) of samples by a specific radioimmunoassay. In a second set of cotyledons, exogenous PGE2 was administered into fetal perfusate, and pressure was monitored as a function of time. These experiments gave the following results: 1) During the initial 20 min., a constant level of PGE2 (2.3-4.4 pg/ml) was maintained in both perfusates. At 3 hrs., the concentrations increased to about 110 ng/ml on the fetal side and 30 ng/ml on the maternal side. The total amount of PGE2 accumulated in the fetal and maternal reservoirs reached to 10.16 and 7.03 ng, respectively. 2) PGE2 (10-150 ng/ml) increased the feto-placental perfusion pressure in a concentration dependent manner. At 150 ng/ml, the pressure increased to 125-240% of control pressure observed at the beginning of the experiment. These studies suggest that a) placental trophoblast has the capacity for the synthesis and release of PGE2 into fetal and maternal circulations; b) PGE2 exhibits differential effects in the placental and uterine blood vessels, vaso-constriction in placental vessels and vasodilation in uterine blood vessels, and (c) PGE2 exhibits dual effects on blood vessels possibly by activating two different subtypes of PG-receptors.

Adult↗
PubMed1996

Differentiation of NG108-15 neuroblastoma cells by serum starvation or dimethyl sulfoxide results in marked differences in angiotensin II receptor subtype expression.

Differentiation of NG108-15 neuroblastoma cells following exposure to either 1.5% dimethyl sulfoxide (DMSO)/0.5% fetal bovine serum (FBS) or serum starvation resulted in significant differences in angiotensin (AT) receptor levels and the AT1/AT2 receptor ratio. When NG108 cells were differentiated for 4 days with DMSO/low serum, the number of AT binding sites increased 30-fold compared with the binding levels on undifferentiated (blast) cells. However, cells differentiated by serum starvation for 4 or 14 days resulted in only a modest 2.5- and fivefold increase in AT receptor levels, respectively, over the levels seen with the undifferentiated cells. KD values for all treatment conditions were not significantly different (0.71 +/- 0.11 nM, p = 0.06). Using the AT1 and AT2 isoform-specific receptor antagonists losartan and PD123319, the relative numbers of AT receptor subtypes on undifferentiated and differentiated cells were determined by competitive inhibition against 125I-[Sar1,Ile8]-angiotensin II (sarile). A majority of the AT receptors on undifferentiated NG108 cells were the AT1 subtype (AT1/AT2 receptor ratio of 8:3). Differentiation by serum starvation and DMSO/low serum treatment resulted in fivefold and 30-fold increases in AT receptor levels, respectively, compared with the levels seen with the undifferentiated cells. Although serum starvation increased the total number of AT1 and AT2 receptors, it did not significantly alter the AT1/AT2 receptor ratio. In contrast, differentiation with DMSO/low serum both increased the total number of AT1 and AT2 receptors and reversed the AT1/AT2 receptor ratio (1:3). The increase in AT receptors following differentiation with DMSO/low serum for 4 days was largely accounted for by an 80-fold increase in the AT2 receptor level. Previous studies by Tallant at al. (1991) and Bryson et al. (1992) reported increased AT2 receptor expression following neuroblastoma differentiation with dibutyryl cyclic AMP and DMSO/low serum, respectively, and suggested a role for the AT2 receptor in neuronal differentiation. In the present study, we have extended these earlier observations by demonstrating that the method of differentiation significantly affects both the AT receptor level and the ratio of AT1 to AT2 receptor expression. Finally, our findings indicate that the AT2 receptor is expressed as a consequence of neuronal maturation and dose not mediate morphological differentiation.

Binding, Competitive↗
PubMed1996

Effects of fetal pH on local anesthetic transfer across the human placenta.

BACKGROUND: Fetal acidemia increases umbilical venous bupivacaine concentrations in the in situ rabbit model. The authors studied the effects of decreasing fetal pH on the rate of maternal to fetal (M-->F) clearances of lidocaine, bupivacaine, 2-chloroprocaine, and antipyrine (a nonionic marker of placental transfer) across the isolated, dual perfused, human placental cotyledon. METHODS: Maternal to fetal clearances of bupivacaine, lidocaine, 2-chloroprocaine, and antipyrine were determined at fetal pH (7.4), during progressive fetal acidemia (pH 7.2-->7.0-->6.8), and after recovery to fetal pH 7.4 in experiments with both low protein state and in those with in vivo maternal and fetal protein-binding potentials. RESULTS: Placental transfer of all three agents increased linearly as the fetal pH decreased. Antipyrine transfer was unaffected. Clearance of lidocaine and bupivacaine, but not 2-chloroprocaine, returned to baseline when fetal pH was restored to 7.4. When maternal and fetal protein-binding potentials were increased, clearance at fetal pH 7.4 of bupivacaine, but not lidocaine, decreased significantly. During fetal acidemia, the transfer of both agents increased, but to a lesser extent than in the low protein concentration experiments. CONCLUSIONS: Increasing the pH difference between maternal and fetal perfusates promotes M-->F passage of unionized lidocaine, bupivacaine, and 2-chloroprocaine. This likely results from an increased proportion of ionized local anesthetic in the acidemic fetal perfusate and consequent widening of the M-->F concentration gradient of the unionized form. Transfer of lidocaine and bupivacaine was limited by the maternal protein binding.

Anesthetics, Local↗
PubMed1996

Tuberculoma presenting as an en plaque meningioma. Case report.

Intracranial tuberculomas generally present as either solitary or multiple lesions in the brain parenchyma. They are characterized by a ring-enhancing area on either computerized tomography scans or magnetic resonance images. A case is presented in which an intracranial tuberculoma was dural based and had an appearance similar to an en plaque meningioma.

Adult↗
PubMed1996

Burr hole neuroendoscopic fenestration of quadrigeminal cistern arachnoid cyst: technical case report.

Arachnoid cysts of the quadrigeminal cistern have been managed by cyst shunting and craniotomy with cyst fenestration. Two children are presented who underwent successful burr hole neuroendoscopic fenestration of symptomatic quadrigeminal plate cysts. The literature is reviewed with regard to the treatment of quadrigeminal arachnoid cysts, and the neuroendoscopic management of these cysts is described.

Adolescent↗
PubMed1995

Bupivacaine transfer across the human term placenta. A study using the dual perfused human placental model.

BACKGROUND: Bupivacaine is widely used for obstetric analgesia, yet published information on the mechanism of human placental bupivacaine transfer is sparse. The dual perfused human placental model was used to elucidate the factors governing the placental transfer of bupivacaine. METHODS: Bupivacaine transfer was studied using the recirculating (closed) model and the single pass (open) model. Single placental cotyledons were perfused with either heparinized Krebs-Ringer's buffer (KRB) supplemented with human albumin (fetal and maternal circuits) or 100% fresh frozen plasma (maternal circuit) to control the bupivacaine protein binding in those circuits. In the open model, bupivacaine clearance was compared before and after being subjected to either increasing concentrations of bupivacaine or its structural analog, mepivacaine. RESULTS: For those studies in which the maternal and fetal protein binding was equal, the maternal to fetal (M-->F) transfer was significantly greater (P < 0.05) than that in the fetal to maternal (F-->M) direction. When the perfusates were modified to simulate actual in vivo plasma protein concentrations, bupivacaine transfer was shown to be related to the degree of protein binding found in the two circuits. In the open studies, bupivacaine transfer was similar at all concentrations investigated, unaffected by mepivacaine, and related to the pH of the fetal perfusate. A concentration effect was seen within the placental tissue at the end of the experiment. CONCLUSIONS: Bupivacaine placental transfer characteristics suggest passive diffusion rather than active drug transport and appear to be influenced by the maternal and fetal plasma protein binding, fetal pH, and placental uptake.

Antipyrine↗
PubMed1995

Advance directives in the medical intensive care unit of a community teaching hospital.

STUDY OBJECTIVE: To evaluate the frequency with which advance directives (ADs) are available at the time of admission and their impact on subsequent care in a medical intensive care unit (MICU) setting before and 9 months after the implementation of the Patient Self-Determination Act (PSDA). DESIGN: Prospective nonrandomized cohort data collection and analysis. SETTING: Thirteen-bed MICU of community teaching hospital providing primary and referred care. PATIENTS: Consecutive admissions during 2-month periods separated by 1 year: August-September 1991 (91) and August-September 1992 (92). MEASUREMENTS: The following were assessed: the presence and type or absence of AD at the time of admission; the presence or absence of a written order to limit resuscitation (WO-R) during the MICU stay; duration of MICU stay in hours; outcome; and combined duration of use or administration of seven selected interventions. MAIN RESULTS: Fifteen of 133 patients (11.3%) in the 91 group and 15 of 171 patients (8.8%) in the 92 group presented with an AD. This difference was not significant (p = 0.578). Most patients in both groups (75.9% in 91 and 80.1% in 92) presented without an AD and did not have a WO-R during their MICU course. In addition, most patients who did present with an AD, 11 of 15 (73.3%) in the 91 group and 14 of 15 (93.3%) in the 92 group, did not have a WO-R. A subgroup of older and more severely ill patients in both cohorts was identified; they did not present with an AD but subsequently a WO-R was established. These patients had the highest mortality, about 40%, when compared with the overall mortality of 8.2%. CONCLUSION: Advanced directives were infrequently available and had little impact on the pattern of care.

Advance Directives↗