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Biomedical subjects

W R Francis

Publications and source records attributed to W R Francis.

At least 19 recordsLinked to original sources
PubMed1997

Percutaneous absorption of vanilloids: in vivo and in vitro studies.

The percutaneous absorption of three highly lipophilic analogs of capsaicin--vanillylnonanamide (VN), olvanil, and NE-21610--was measured in vivo in the CD:VAF rat, and in vitro through excised CD: VAF and SkH:Fz rat skin and human cadaver skin. Absorption and skin metabolism were monitored by radiolabel techniques. The rank order of penetration in all species was VN > olvanil > NE-21610, in accordance with that expected from their physical properties. Rat skin was more permeable than human skin by factors ranging from 4 to 8 for VN, 10 to 20 for olvanil, and approximately 10 to 100 for NE-21610. All three compounds were extensively metabolized during passage through fresh SkH:Fz rat skin, with the primary route of degradation for at least two of the compounds involving hydrolysis of the amide bond (the metabolites of NE-21610 were not identified). For the in vitro studies a range of receptor solutions was employed to determine a set of conditions that best mimicked in vivo absorption. The results with phosphate-buffered saline containing a preservative and 1-6% polyoxyethylene-20 oleyl ether (Oleth-20) were in good agreement with in vivo results for all three compounds for periods up to 24 h post-dose; after this time, in vivo absorption rates declined but in vitro rates remained relatively constant. Buffered saline or saline containing 0.5% bovine serum albumin led to marked underestimates of in vivo penetration for olvanil and NE-21610, whereas a 1:1 ethanol: water solution led to gross overestimates of the in vivo absorption rates for all three compounds.

Animals↗
PubMed1994

Improving the sensitivity of in vitro skin penetration experiments.

The institution of a readily-implemented sample screening and data handling procedure for in vitro skin penetration studies yields substantial improvements in sensitivity for distinguishing between formulations, treatments, penetrants, etc. The procedure involves four steps: 1) prescreen the tissue samples to determine their intrinsic permeability; 2) apply treatments using a randomized complete block (RCB) design, with blocking by tissue permeability; 3) apply a variance-stabilizing transformation to the penetration data, followed by outlier testing; and 4) analyze the transformed data according to an RCB analysis of variance, using tissue permeability as the blocking variable. For penetration studies in which high sample variability is a concern, the above procedure commonly yields a sensitivity advantage of several-fold versus alternative methods of comparison.

Humans↗
PubMed1991

Capsaicin desensitization to plasma extravasation evoked by antidromic C-fiber stimulation is not associated with antinociception in the rat.

The relationship of capsaicin desensitization to the antinociception produced by acute capsaicin administration was studied in the rat. Cutaneous application of 1% capsaicin (3 x/day) for 1 day antagonized plasma extravasation evoked by either 5% capsaicin applied to the dorsal surface of the hindpaw or antidromic stimulation of the saphenous nerve. Treatment with either 1% or 5% capsaicin (3 x/day) for up to 4 days failed, however, to produce thermal antinociception as measured by the rat paw-withdrawal procedure. In contrast, intracutaneous injection of 100 micrograms capsaicin produced marked increases in paw-withdrawal response latencies for up to six hours after injection. These data demonstrate a dissociation between block of cutaneous plasma extravasation and thermal antinociception in the rat. The data provide in vivo evidence that desensitization of peripheral nociceptors by capsaicin cannot account for the antinociception observed following acute capsaicin administration. Finally, these data support the notion that some pharmacologic actions of capsaicin in the rat can be dissociated from frank neurotoxicity on the basis of concentration or dose.

Animals↗
PubMed1990

Embryonal disposition of salicylate: in vivo-in vitro comparisons.

The distribution of salicylate to embryonal compartments for in situ and in vitro rat embryos under equivalent exposure conditions, and salicylate disposition in the in vivo mid-gestation embryo and late gestation fetus, were compared. Pregnant Sprague-Dawley CD rats were exposed to steady-state blood levels of salicylate by infusing 14C-salicylic acid iv for a 24 hour period from gestation day 11.5 to 12.5. Cultured Sprague-Dawley rat embryos (in medium consisting of 100% male rat serum) were exposed to the steady-state 14C-salicylate concentration achieved in maternal serum in vivo for the same 24 hour developmental period. At the end of the exposure period radioactivity in visceral yolk sac, extra-embryonic fluid and embryos, and in maternal tissues, was measured. The distribution of salicylate to embryonal tissues was statistically comparable in vivo and in vitro, although the embryos in vitro accumulated slightly (but not significantly) less of the chemical. There was considerable binding of salicylate by maternal serum and culture medium proteins: less than 20% of the chemical was free at the 40 micrograms/ml concentration used in this experiment. Consequently, the salicylate concentration in embryonal compartments appeared to be quite low when compared to the surrounding serum/medium, but was actually equal to or greater than the concentration of unbound salicylate in serum or culture medium. The proportion of free salicylate in serum increased at concentrations higher than 40 micrograms/ml, resulting in somewhat higher concentrations of salicylate in in vitro embryos and extraembryonic fluid (as compared to medium) when cultured in the presence of 200 or 400 micrograms/ml salicylate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Urinary and bladder responses to immobilization in male rats.

Immobilization of groups of five to nine male rats for 2-5 days results in a 50% increase in urinary bladder fresh weight compared with normally caged controls. The increase in urinary bladder weight was not due to tissue oedema and was accompanied by epithelial hyperplasia in some urinary bladders. Immobilization did not alter total urine volume, but it did decrease the frequency of urine voiding and doubled the mean urine weight/voiding. Thus, bladder distention caused by the increased volume per voiding caused a rapidly induced increase in bladder tissue growth, and was accompanied by an increase in bladder epithelial cell division.

Animals↗
PubMed1989

Traumatic spondylolisthesis of the axis.

Hanging, a common method of execution, began in antiquity and continues to this date. Unfortunately, the exact cause of a victim's demise was not always obvious, and many victims died as the result of asphyxiation from the hangman's noose. In the latter part of the 19th century, scientific curiosity led to autopsy studies of the cervical spine; Paterson in 1890 first described the lethal lesion. Experimental work in 1913 demonstrated that when the hangman's knot was placed beneath the chin, death rapidly occurred because of a traumatic spondylolisthesis of the second cervical vertebra. This knot placement then became standard as the most efficient method of execution. It was not until the mid-20th century that the similarity between judicial and civilian injury was recognized. The reports were infrequent, and most of the pars interarticularis fractures resulted from automobile accidents in which the victim was thrown forward and struck his or her face against the windshield which caused sudden violent hyperextension. The similarity between civilian and vehicular injuries was recognized in 1965 by Schneider who, together with his associates, reported eight cases; it was this group who introduced the term "hangman's fracture". Garber presented his thoughts on this subject, noting that there was a difference between the forces generated by judicial hanging and those caused by motor vehicle accidents and other similar civilian injuries. The former results in axial loading and hyperextension, and, rarely, in flexion or axial loading. Since the lesion occurs at the pars interarticularis of C2, Garber suggested that a more appropriate term might be traumatic spondylolisthesis of the axis.

Axis, Cervical Vertebra↗
PubMed1988

Treatment of cervical kyphosis in children.

Children with severe cervical kyphosis present a difficult treatment challenge. The most common etiology of this deformity is extensive laminectomies, especially associated with postlaminectomy irradiation. The deformity can be rapidly progressive leading to neurologic involvement. With intact posterior elements, kyphosis can occur as a result of congenital, traumatic, metabolic or neoplastic processes. Treatment is directed towards early recognition, arrest of the progression of deformity, and improvement of neurologic symptoms. Patients with loss of posterior elements can be treated effectively by preoperative traction and a single-staged anterior release with strut fusion. Patients with intact posterior elements require preoperative traction, initial posterior osteotomies with intraoperative traction, then an anterior release with strut fusion. All patients need rigid postoperative halo immobilization for a minimum of 3 to 4 months to maintain position. Using these techniques, nine patients were treated surgically with satisfactory outcomes.

Adolescent↗
PubMed1988

Physiological model for tissue glutathione depletion and increased resynthesis after ethylene dichloride exposure.

Ethylene dichloride (EDC) is metabolized by two competing pathways both of which consume glutathione (GSH). EDC undergoes oxidation to form chloroacetaldehyde (CAA) which is detoxified by GSH and also reacts directly with GSH to form 2-(s-chloroethyl)-GSH. A physiological pharmacokinetic model developed for EDC was extended to describe tissue GSH turnover and its depletion after EDC exposures. This GSH model was necessary to keep track of GSH concentrations with time, as EDC metabolism is affected by GSH status. Reactions of GSH with EDC and GSH with CAA were defined as second-order. Steady-state GSH formation was modeled as zero-order and GSH loss as first-order. GSH rebound effects after its depletion were controlled by a GSH synthetase reaction, which allowed time- and GSH concentration-dependent feedback for increased GSH resynthesis. The model was developed for liver GSH in the rat and was extrapolated to include the lung. Allometric scaling was used to extrapolate the model to other animal species. Experimental observations in the rat and mouse were consistent with model predictions.

Animals↗
PubMed1987

Effect of dietary carbohydrate type and content on the response of male rats to dietary sodium saccharin.

The role of dietary carbohydrate composition and concentration in the response of male rats to sodium saccharin (NaS) was ascertained by comparing the response to 5% dietary NaS in rats given diets containing 65% starch, 50% sucrose together with 15% starch, 65% glucose, or 3% sucrose. NaS induced similar levels of caecal enlargement and increases in urine volume and bladder mass when given with any of the three forms of carbohydrate at 65% in the diet. However with the 3% sucrose diet, NaS caused a lesser caecal enlargement and no increase in urine volume or bladder mass. These findings suggest that NaS not only inhibits saccharide hydrolysis but also inhibits glucose transport. The significance of these findings in relation to NaS-associated bladder tumours is discussed.

Animals↗
PubMed1986

Effect of N-nitroso-n-butyl-(4-hydroxybutyl)amine exposure on the changes in mineral disposition caused by trisodium nitrilotriacetate.

Male Fischer 344 rats were used to determine effect of consumption of 0.5% N-nitroso-n-butyl-(4-hydroxybutyl)amine (BNN) in the drinking-water for 2 wk on the response to 0.02, 0.2 and 2.0% trisodium nitrilotriacetate (Na3 NTA . H2O) in the diet in terms of urinary mineral excretion, bladder mass and bladder mineral concentrations. The primary objective of the study was to determine whether exposure of rats to an initiating dose of a bladder carcinogen (BBN) alters the threshold dose of Na3NTA . H2O required to alter urinary or bladder mineral concentrations or the dose-response to NTA. Such alterations are considered to be necessary precursors for changes in bladder morphology in rats fed NTA in chronic toxicity studies (Anderson, Bishop & Campbell, CRC Crit. Rev. Toxicol. 1985, 15, 1). The results demonstrated that BBN exposure caused an increase in bladder mass and bladder-tissue Zn concentration. However, BBN pretreatment did not have any effect on Na3NTA . H2O metabolism, the threshold dose of Na3NTA . H2O required to attain the necessary conditions for induction of bladder toxicity by NTA, or the dose-response relationships for NTA's effects on any parameter examined. From these data, it is concluded that it is unlikely that NTA would show a different threshold or dose-response for bladder tumour promotion than for its tumorigenicity at this site, which has been demonstrated previously (National Cancer Institute, DHEW Publication No. (NIH) 77-806, 1977).

Acetates↗
PubMed1986

Trypsin inhibitor ingestion-induced urinary indican excretion and pancreatic acinar cell hypertrophy.

Sodium saccharin (NaSacc) has been shown to be a protease inhibitor and to induce an increase in urinary indican, which is a product that is dependent on microbial metabolism of tryptophan. These findings suggest that urinary indican might provide a noninvasive marker of increased pancreatic acinar cell size associated with plant trypsin inhibitor ingestion. The results demonstrate the 7.5% of dietary NaSacc, which increases urinary indican, also increases relative pancreas mass (g/kg body weight), and that these effects are not induced by intravenous infusion of NaSacc. Dietary soybean trypsin inhibitor in the dose range of 17-713 mg/100 g diet was associated with parallel dose-dependent increases in urinary indican and pancreatic acinar cell size (assessed histologically). These findings suggest that measurement of relative urinary indican excretion (microgram/g diet ingested) can provide a noninvasive marker of increased pancreatic acinar cell size in rats that ingest compounds which inhibit digestive proteases.

Animals↗
PubMed1985

Home health care: drug-related problems detected by consultant pharmacist participation.

Consultant pharmacists conducted a drug history and regimen review on one-fourth of the patient population served by a community hospital-based home health department. About one-third of study patients had inappropriately stopped taking their medications; over one-fourth of the study patients had changed their schedule or dose without health professional consultation. Fifteen percent of all medications were duplications, and only 8% of prescription medications were correctly identified by name. Consultant pharmacist activities that could reduce drug-related problems were identified as drug therapy consultation with patients and staff, drug regimen review, drug information, and patient medication education.

Consultants↗
PubMed1984

Renal pelvic and ureteral dilatation in male rats ingesting trisodium nitrilotriacetate.

Renal pelvic and proximal ureteral dilatation has been observed in male Charles River (CD) and Fischer 344 rats ingesting comparable doses of Na3NTA X H2O. Ureteral dilatation is accompanied by epithelial surface ulceration and erosion. Taken together with previous work (Anderson, Alden & Merski, Fd Chem. Toxic. 1982, 20, 105), these findings demonstrate that the ingestion of high doses of NTA results in similar effects on the transitional epithelium throughout the urinary tract.

Acetates↗
PubMed1983

Atlantal fracture in a child through congenital anterior and posterior arch defects. A case report.

A five-year-old boy sustained a vertical compression injury to the occiput, initial findings were consistent with a cervical spine injury. Evaluation, including plain films, tomograms, and CT scanning, confirmed a C1 fracture through congenital anterior and posterior arch defects. Flexion and extension tomograms showed this rare lesion to be stable, and no surgical intervention was required. Because congenital anomalies of the cervical spine can be confused with traumatic lesions, thorough evaluation is warranted. Treatment should be based on signs of instability, if present.

Atlanto-Axial Joint↗
PubMed1981

Traumatic spondylolisthesis of the axis.

A series of 123 patients suffering traumatic spondylolisthesis of the axis is reported. This lesion is associated with extension and axial loading injury, and there is a high incidence of injuries of the face or scalp and of associated fractures of the upper cervical spine. There is a low incidence of neurological injury, which seems paradoxical in the presence of what appears to be gross instability, but protection from extremes of flexion and extension may be adequate treatment. Union is usual regardless of displacement. Traction is a safe means of treatment, but early waking in a halo support reduces time in hospital without jeopardizing the result. Operation is needed only for chronic instability with or without pain, and anterior interbody fusion of C2--3 is than preferred in order to preserve rotation at the atlanto-axial joints.

Adolescent↗
PubMed1981

MAC regulations: their predicted economic impact on pharmaceutical reimbursement.

The Maximum Allowable Cost (MAC) regulations, Part 19 of Subtitle A of Title 45 of the Code of Federal Regulations, were promulgated as a method of cost containment applicable to a component of the escalating health care expenditures. This study predicted the economic impact of the MAC regulations on the Medicaid program of Georgia. Reimbursements for Medicaid prescription drug products by the Georgia Department of Medical Assistance for 1976-1977 were compared with the reimbursements for drug products that would have been paid under the MAC regulation limitations had the MAC regulations been in force during the time period studied. The cost per unit of a purposive sample of 386 drug entities sorted into eight code groups was compared with the MAC-regulated cost per unit reimbursements. Significant differences in cost were noted for three of the eight code groups. For these groups, reimbursements of before MAC-regulated drug product cost per unit were greater than reimbursements for predicted MAC-regulated drug product cost per unit. Further analysis of the data predicted a reduction of reimbursements for the eight classes of prescription drug products studied to be 24.42%. This reduction compares favorably with the projected savings of 22-36% reported by the Task Force on Prescription Drugs.

Cost Control↗