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Biomedical subjects

R Griffin

Publications and source records attributed to R Griffin.

At least 19 recordsLinked to original sources
PubMed2005

Implications of increased tumor blood flow and oxygenation caused by mild temperature hyperthermia in tumor treatment.

In many past clinical studies in which hyperthermia enhanced the efficacy of radiotherapy, the tumor temperatures could be raised only to 40-42 degrees C range in most cases. The heat-induced cell death, cellular radiosensitization, and vascular damage induced by such mild temperature hyperthermia (MTH) are likely to be insignificant despite the increased response of tumors to radiotherapy. Heating rodent tumors at 40-42 degrees C was found to cause an enduring increase in blood flow and oxygenation in the tumors. Recent studies with canine soft tissue sarcoma and human tumor clinical studies also demonstrated that MTH improves tumor oxygenation, and enhances response of the tumors to radiotherapy or chemoradiotherapy. The increased blood flow and vascular permeability caused by MTH may also improve the delivery of various therapeutic agents such as chemotherapy drugs, immunotherapeutic agents and genetic constructs for gene therapy to tumor cells. MTH as a means to potentiate the efficacy of radiotherapy and others warrants further investigation.

Animals↗
PubMed2002

Willingness to pay for flood and ecological risk reduction in an urban watershed.

Urban watershed managers frequently must address alternative policy goals; flood control and ecological risk reduction. This study combines hydrologic models of flood control and biotic models of ecologic risk with economic models of willingness-to-pay and psychological models of risk processing and planned behavior to evaluate these two alternative policy objectives. The findings reveal that flood risk exposure, especially for those individuals who would remain outside the 100 year flood plain if the project were enacted, does influence the financial support that local residents would be willing to make to a flood control project. Other important determinants include demographic factors such as income, and attitudinal measures of the respondent. Expanding the scope of the project to include ecological risk reduction does not, however, appear to change the average willingness-to-pay for a project.

Demography↗
PubMed2001

Improvement in health care utilization and pulmonary function with fluticasone propionate in patients with steroid-dependent asthma at a National Asthma Referral Center.

The impact of switching from other inhaled corticosteroids to fluticasone propionate was studied in patients with severe oral-steroid-dependent asthma over a 1-year period. In this open-label prospective study, patients on maintenance doses of oral and inhaled steroids were referred to a national asthma treatment center and were switchedfrom their previous inhaled corticosteroid to fluticasone propionate 880 microg BID. Compared with data collected from the year prior to enrollment, treatment with fluticasone propionate resulted in significant improvements in pulmonary function, oral steroid requirements, and health resource utilization. In addition, five patients were completely weaned off oral steroids.

Administration, Inhalation↗
PubMed2001

A prodrug approach to the design of cRaf1 kinase inhibitors with improved cellular activity.

Earlier we reported potent cRaf1 kinase inhibitors with a key acidic phenol pharmacophore that had, at best, adequate cellular efficacy. To improve the cellular potency, phenol isosteres and prodrugs were investigated. Many phenol isosteres were synthesized and tested, but failed to provide adequate enzyme potency. A prodrug approach resulted in a 2- to 17-fold improvement over the parent compound in cell-based efficacy.

Antineoplastic Agents↗
PubMed2000

Classical and El Tor biotypes of Vibrio cholerae differ in timing of transcription of tcpPH during growth in inducing conditions.

Two protein pairs in Vibrio cholerae, ToxRS and TcpPH, are necessary for transcription from the toxT promoter and subsequent expression of cholera virulence genes. We have previously shown that transcription of tcpPH in classical strains of V. cholerae is activated at mid-log-phase growth in ToxR-inducing conditions, while transcription of tcpPH in El Tor strains is not. In this study, we showed that while transcription of tcpPH differs at mid-log-phase growth in ToxR-inducing conditions between the biotypes, transcription is equivalently high during growth in AKI conditions. We used tcpPH::gusA transcriptional fusions to quantitate expression of tcpPH in each biotype throughout growth in ToxR-inducing conditions and showed that although transcription of tcpPH is reduced at mid-log-phase growth in an El Tor strain, transcription is turned on later in growth to levels in excess of those in the classical strain (although cholera toxin is not produced). This suggests that the difference in expression of cholera virulence factors in response to ToxR-inducing conditions between the El Tor and classical biotypes of V. cholerae may be related to the timing of transcription of tcpPH rather than the absolute levels of transcription.

Artificial Gene Fusion↗
PubMed1998

Neonatal outcome and mode of delivery after epidural analgesia for labour with ropivacaine and bupivacaine: a prospective meta-analysis.

In this prospective meta-analysis, we have evaluated the effect of epidural analgesia with ropivacaine for pain in labour on neonatal outcome and mode of delivery compared with bupivacaine. In six randomized, double-blind studies, 403 labouring women, primigravidae and multiparae, received epidural analgesia with ropivacaine or bupivacaine 2.5 mg ml-1. The drugs were administered as intermittent boluses in four studies and by continuous infusion in two. Apgar scores, neurological and adaptive capacity scores (NACS), degree of motor block and mode of delivery were recorded. The studies were designed prospectively to fit meta-analysis of the pooled results. Results showed similar pain relief and consumption of the two drugs. In the vaginally delivered neonates, NACS scores were approximately equal for both groups at 2 h, but at 24 h there were fewer infants with NACS less than 35 in the ropivacaine compared with the bupivacaine group (2.8% vs 7.6%; P < 0.05). Spontaneous vaginal deliveries occurred more frequently overall with ropivacaine than with bupivacaine (58% vs 49%; P < 0.05) and instrumental deliveries (forceps and vacuum extraction) less frequently (27% vs 40%; P < 0.01), while the frequency of Caesarean section was similar between groups. The intensity of motor block was lower with ropivacaine. There were no significant differences in adverse events.

Adolescent↗
PubMed1998

Pulmonary vascular pressures of strenuously exercising Thoroughbred horses after administration of phenylbutazone and frusemide.

The present study was carried out to examine the effects of phenylbutazone treatment on the pulmonary haemodynamic effects of frusemide in strenuously exercising horses. Using catheter mounted manometers, whose in vivo signals were referenced at the point of the shoulder, heart rate, right atrial, right ventricular and pulmonary vascular pressures were measured in 3 different sets of experiments. Seven Thoroughbreds were subjected to 1) control (no medications), 2) frusemide control and 3) phenylbutazone + frusemide. The experiments were carried out in random order and were separated by 7 days. Measurements were made at rest and during incremental exercise performed on a treadmill set at 3.5% uphill grade. In the frusemide control experiment, horses received frusemide 250 mg i.v., 4 h pre-exercise. In the phenylbutazone + frusemide experiment, horses received 4 i.v. injections of phenylbutazone (4.4 mg/kg bwt) at 12 h intervals. Twenty-four hours after the last phenylbutazone injection, horses received frusemide 250 mg i.v. and exercise was performed 4 h later. This latter regimen mimics prevailing veterinary practice at Illinois racetracks. The highest work intensity (14.2 m/s, 3.5% uphill grade) elicited maximal heart rate of horses. Significant right atrial, as well as pulmonary arterial, capillary and venous hypertension occurred with exertion in all 3 experiments. However, in the frusemide-control and the phenylbutazone + frusemide studies, the exercise induced rise in mean right atrial and pulmonary vascular pressures was significantly (P<0.05) attenuated in comparison with that in the control experiments. Statistically significant differences were not found between the frusemide control study and the phenylbutazone + frusemide study either at rest or during any level of exertion. Therefore, it was concluded that the phenylbutazone treatment in our study did not mitigate the pulmonary haemodynamic effects of frusemide in strenuously exercising Thoroughbred horses.

Animals↗
PubMed1997

Soluble human urokinase receptor is composed of two active units.

The mechanism by which single-chain urokinase (scuPA) binds to its receptor (uPAR) is incompletely understood. We report that a fragment comprising the first domain of recombinant soluble uPAR (sDI) as well as a fragment comprising the remaining domains (sDII-DIII) competes with the binding of recombinant full-length soluble uPAR (suPAR) to scuPA with an IC50 = 253 nM and an IC50 = 1569, respectively. sDII-III binds directly to scuPA with Kd = 238 nM. Binding of scuPA to each fragment also induces the expression of plasminogen activator activity. sDI and sDII-DIII (200 nM each) induced activity equal to 66 and 36% of the maximum activity induced by full-length suPAR (5 nM), respectively. Each fragment also stimulates the binding of scuPA to cells lacking endogenous uPAR. Although scuPA binds to sDI and to sDII-DIII through its amino-terminal fragment, the fragments act synergistically to inhibit the binding of suPAR and to stimulate plasminogen activator activity. Furthermore, sDII-DIII retards the velocity and alters the pattern of cleavage of sDI by chymotrypsin. These results suggest that binding of scuPA to more than one epitope in suPAR is required for its optimal activation and association with cell membranes.

Humans↗
PubMed1997

Effects of smoking and clinical status on lung function in human immunodeficiency virus (HIV)-seropositive subjects.

Lung function was measured at 3-month intervals for up to 1 yr in a group of Caucasian HIV-seropositive subjects. The objective was to document any deterioration in lung function and seek correlations between such deterioration and smoking history and Centers for Disease Control (CDC) status. Ninety-nine subjects were studied at enrollment; 43 were followed-up (mean duration 9 +/- 3 months). Ninety-five of the 99 enrolled subjects remained free of HIV-related respiratory disease and were included in the analysis. At enrollment, carbon monoxide diffusing capacity (TLCO) was significantly lower than predicted in non-smokers, smokers and ex-smokers (88, 77 and 88%, respectively, P < 0.001). The TLCO measurements in the smoking group were significantly lower than those of the life-long non-smoking subjects (P < 0.01). Residual volume (RV) was significantly higher than predicted in smokers (111%, P = 0.02). During follow-up, all three groups demonstrated significant declines in TLCO (7%, P = 0.01; 9%, P = 0.005; 13%, P < 0.001, respectively), and increases in RV (9%, P = 0.03; 13.5%, P = 0.02, 22%, P = 0.02, respectively). At enrollment, significantly lower than predicted values of TLCO were observed in groups stratified by CDC criteria: in asymptomatic HIV-seropositive subjects (CDC 11) 89%, P = 0.01; persistent generalized lymphadenopathy (PGL) 84%; AIDS-related complex (ARC) 81%; and in non-pulmonary AIDS (IV C1) 69%, P = 0.0001, respectively. Residual volume was significantly higher than predicted in CDC II (114%, P = 0.05). During follow-up, TLCO fell in groups PGL and ARC by 7 and 9%, respectively, while RV increased in groups CDC II, PGL and ARC by 17, 15 and 8%, respectively. Only the TLCO decline in PGL showed any linkage to clinical deterioration. This study demonstrates deficits at enrollment, and a continuing decline of TLCO and increase in RV in HIV-seropositive subjects without overt lung disease.

AIDS-Related Complex↗
PubMed1997

Pulmonary vascular pressures of strenuously exercising Thoroughbreds after administration of varying doses of frusemide.

The frusemide dose-response for attenuation of exercise-induced pulmonary capillary hypertension was studied in 7 healthy, exercise-conditioned Thoroughbred horses using previously described haemodynamic procedures. Four different doses of frusemide were tested: 250 mg regardless of bodyweight (amounting to 0.56 +/- 0.03 mg/kg bwt), 1.0 mg/kg bwt, 1.5 mg/kg bwt and 2.0 mg/kg bwt. Frusemide was administered i.v., 4 h before exercise. Haemodynamic data were obtained at rest and during treadmill exercise performed at 14.2 m/s on a 3.5% uphill grade; this workload elicited maximal heart rate of horses. Airway endoscopy was performed post exercise to detect exercise-induced pulmonary haemorrhage (EIPH). In standing horses, frusemide administration resulted in a significant (P<0.05) decrease in mean pulmonary arterial, pulmonary capillary and pulmonary artery wedge pressures, but significant differences among the various frusemide doses were not observed. In the control experiments, exercise caused significant increments in the right atrial as well as pulmonary arterial, wedge, and capillary pressures, and all horses experienced EIPH. Following frusemide administration, the exercise-induced rise in right atrial and pulmonary vascular pressures was significantly attenuated, but significant differences between the frusemide doses of 250 mg, 1.0 mg/kg, and 1.5 mg/kg were not discerned and all horses remained positive for EIPH. Although a further significant (P<0.05) attenuation of the exercise-induced rise in pulmonary capillary blood pressure occurred when frusemide dose increased from 250 mg to 2.0 mg/kg bwt, all horses still experienced EIPH. It is concluded that a linear response to increasing frusemide dosage in terms of attenuation of the pulmonary capillary hypertension does not exist in strenuously exercising Thoroughbred horses.

Animals↗
PubMed1996

Pulmonary vascular pressures of strenuously exercising thoroughbreds after administration of phenylbutazone.

OBJECTIVE: To determine the effects of phenylbutazone administration on heart rate and right atrial and pulmonary vascular pressures in Thoroughbreds during rest and during exercise performed at maximal heart rate. ANIMALS: 7 healthy, exercise-conditioned Thoroughbreds. PROCEDURE: Horses were studied on 3 occasions: without medication [control], after i.v. administration of phenylbutazone (4.4 mg/kg of body weight) at 12-hour intervals for 2 days and a final dose given 1 hour before exercise, and after i.v. administration of phenylbutazone for 2 days in the same manner, but with the final dose given 24 hours before exercise. Horses were studied at rest and during exercise performed at maximal heart rate on a treadmill. Right atrial and pulmonary vascular pressures were measured with catheter-tip manometers referenced at the point of the shoulder. RESULTS: We did not detect significant differences in heart rate or right atrial and pulmonary vascular pressures among values recorded when horses were not given medication and values recorded when phenylbutazone was administered by either regimen. Exercise-induced pulmonary hemorrhage occurred in 6 of the 7 horses regardless of whether phenylbutazone was administered or the dosage regimen used. CONCLUSIONS: In these Thoroughbreds, phenylbutazone treatment did not modify heart rate or right atrial and pulmonary vascular pressures at rest or during exercise capable of eliciting exercise-induced pulmonary hemorrhage. Thus, because phenylbutazone is a potent inhibitor of cyclooxygenase, prostaglandins probably do not play a role in mediating exercise-induced pulmonary hypertension in horses. CLINICAL RELEVANCE: Phenylbutazone administration did not modify the pulmonary capillary hypertension in the strenuously exercising Thoroughbreds, and therefore, is unlikely to alter the prevalence or severity of exercise-induced pulmonary hemorrhage in Thoroughbred race-horses.

Animals↗
PubMed1995

Farm visits and zoonoses.

Recent reports of outbreaks of gastrointestinal illness, such as cryptosporidiosis, associated with visits to farms have drawn attention to the possible risks of acquiring zoonotic infections through contact with farm animals. These risks seem to be small, but it is important that people who work in urban and rural farms, and such establishments as animal sanctuaries where the general public can come into close contact with farm livestock and other animals, should be alerted to the simple precautions needed to prevent transmission of infections.

Adult↗
PubMed1995

MMPI-2 clinical correlates for ten common codes.

A number of researchers have called for the establishment of a Minnesota Multiphasic Personality Inventory-2 (MMPI-2; Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) correlate literature that is based directly on investigations of the revised MMPI. The purpose of this study was to examine clinical correlates found for 9 commonly occurring 2-point codes, each of which contained a minimum of 20 patients, and for 82 profiles that were within-normal-limit (WNL) in a sample of 289 female and 308 male psychiatric inpatients. Major findings indicated that descriptors identified for MMPI-2 based codes were generally similar to the established literature for corresponding codes derived from the original MMPI (Hathaway & McKinley, 1967). In addition, correlates identified for the WNL profile suggest that these patients are less likely to exhibit more chronic symptomatology and to have psychological histories marked by less severe psychological disturbance than other inpatients. Overall, the results of this study represent an initial step in the creation of an MMPI-2 correlate literature.

Journal Article↗
PubMed1994

The effect of position on sacral spread of epidural analgesia.

In parturients, extension of epidural analgesia to include the sacral roots is necessary for adequate analgesia during the second stage of labour and for vacuum extraction and forceps delivery. There is clinical evidence that if the sitting position is adopted after local anaesthetic administration, it impairs the sacral spread of analgesia. An in vitro model representing the lumbar spinal canal has been used to demonstrate how, in the vertical position, a CSF plug can prevent downward spread of local anaesthetic. With the model tilted 25 degrees to the horizontal and also in the full horizontal position downward spread occurs. The effect of a 25 degrees head up tilt on sacral spread of epidural analgesia was compared clinically with the horizontal position. Women requesting epidural analgesia during labour were randomly allocated to receive the first epidural dose either with the head end of the bed tilted 25 degrees head up (n = 30) or remaining horizontal (n = 30). All epidurals were sited at L3/4, a test dose of 2 ml of 0.5% bupivacaine was followed by a main dose of 6 ml of 0.5% bupivacaine. Sacral sensory blockade was greater in the head up group. The difference was significant on the left side (P < 0.05) at 15, 20, and 30 minutes after the main dose. There were more patients with blocks extending to S5 (on either the left or right sides) in the head up group at 15, 20 and 30 minutes (P < 0.05 at 20 and 30 minutes on left side).

Journal Article↗
PubMed1994

Muscle involvement in polyarteritis nodosa: report of a patient presenting clinically as polymyositis and review of the literature.

Muscle symptoms, especially myalgias, appear to be common in patients with polyarteritis nodosa (PAN). We describe a patient who presented with a generalized myopathy and elevated creatine kinase (CK) suggestive of polymyositis. However, subsequent exploratory surgery for an acute abdomen revealed colonic perforation on the basis of PAN. A review of the literature suggests that generalized myopathy and elevated CK are uncommon features of PAN. A muscle biopsy can be a helpful procedure to secure the diagnosis in patients with PAN especially those with myopathies. Strategies for optimizing the choice of biopsy site are discussed.

Creatine Kinase↗