Search PubMed⌕ Search

Biomedical subjects

J Blanchard

Publications and source records attributed to J Blanchard.

At least 109 records · Page 6Linked to original sources

Immunocytochemical characterization of the suprachiasmatic nucleus and the intergeniculate leaflet in the diurnal ground squirrel, Spermophilus lateralis.

The suprachiasmatic nucleus (SCN) and the intergeniculate leaflet (IGL) are retinorecipient structures that play important roles in the expression of circadian rhythmicity. We examined these two structures in a diurnal ground squirrel, Spermophilus lateralis, using immunohistochemical techniques, and cholera toxin-bound horseradish peroxidase. A number of immunoreactive substances are distributed within the ground squirrel SCN in a pattern similar to that reported in many other mammals. These include vasopressin, vasoactive intestinal polypeptide, serotonin, neuropeptide Y (NPY), and glial fibrillary acidic protein. The squirrel SCN differs from that of most other species examined to date in two respects. First, a dense cluster of cells containing immunoreactive L-enkephalin (L-ENK-IR) is observed in the center of the SCN. Second, there is a contralateral, but no ipsilateral, projection from the retina to the SCN. In the lateral geniculate region there is a substantial region that contains NPY-immunoreactive cells and receives a bilateral retinal projection. This region is assumed to be homologous with the IGL described in other mammals. Cells containing L-ENK-IR are distributed throughout the LGN in groups that overlap, but which have a distinctly different distribution than the more extensive groups of NPY-IR cells.

Animals↗

Serum/saliva correlations for theophylline in asthmatics.

Theophylline levels in mixed saliva (both stimulated and unstimulated) were compared with total and free (unbound) serum theophylline levels in 28 asthmatic outpatients using theophylline regularly. Stimulated saliva predicted both total and unbound serum theophylline concentrations within +/- 1 microgram/mL in 62.5% and 92.9%, respectively, of the samples examined. In addition, the total serum levels could be used to predict unbound serum concentrations to within +/- 1 mg/L in 100% of the cases that were examined. These results indicate that saliva levels predict the unbound serum theophylline levels with greater accuracy and precision than they predict total serum theophylline levels. In addition, total serum levels can be used to reliably predict unbound serum levels. The use of mixed stimulated saliva is recommended as a reliable non-invasive method for monitoring unbound serum theophylline levels. The therapeutic range for saliva, which corresponds to the accepted total serum concentration range of 10-20 mg/L, is approximately 5.6-11.3 mg/L.

Administration, Oral↗

Effects of gender on vitamin C pharmacokinetics in man.

The pharmacokinetics of vitamin C (VC) were compared in young and elderly male and female subjects following 500 mg oral doses to each subject in two states of VC nutriture: a depleted state achieved by 4-5 weeks on a diet containing less than 10 mg VC/day and a supplemented state which was achieved following 500 mg/day doses of VC for 3 weeks. The males were taller and heavier than their female counterparts and consequently had a greater body surface area (BSA). The body mass index (BMI) and fat mass did not differ between genders within an age group, whereas only the young females exhibited a greater percent body fat. The males exhibited a larger fat-free mass (FFM) than the females. None of the pharmacokinetic parameters differed due to gender in depleted subjects. In the supplemented state the female subjects exhibited a significantly greater peak VC concentration (Cmax), a longer absorption lag time (tlag), apparent volume of distribution (AVd) in L/kg, clearance (CL) in ml/hr/kg, and renal clearance (CLr) in ml/hr/kg. When AVd, CL, and CLr were expressed in absolute terms (i.e., L or ml/min), no gender-related differences were observed. A stepwise multiple linear regression indicated that Cmax was inversely linearly related to body weight, tlag was directly related to BSA and dose, and AVd (L/kg) was inversely linearly related to BSA. CL (ml/hr/kg) and CLr (ml/hr/kg) were not significantly related to any of the body composition parameters examined. Overall, these results indicate that there are few gender-related differences in the pharmacokinetics of VC in humans and that a portion of the observed differences can be explained by body composition differences between the sexes.

Adipose Tissue↗

Depletion and repletion kinetics of vitamin C in humans.

Depletion and repletion profiles of vitamin C were determined in young and elderly males and females. Plasma vitamin C concentrations were determined upon entry into the study, once each week during a 5-wk period of dietary restriction (10 mg/day) of the vitamin and twice each week during a 2.5-wk period of supplementation with 500 mg/d. The rate constant (K) and the half-life of the depletion phase (t1/2) were determined. Other values calculated included the mean plasma vitamin C concentration in the four subject groups at entry, depleted and supplemented states of vitamin C nutriture. A t test indicated that none of the calculated values differed due to age. In contrast, K was significantly smaller in men, resulting in a longer t1/2. The entry and depleted plasma vitamin C concentrations did not differ due to gender whereas repleted plasma vitamin C concentrations were higher in women than in men. Data analysis indicated that plasma depletion of vitamin C is a first-order process. In addition, t1/2 was inversely related to entry vitamin C levels at concentrations below approximately 85 mumol/L whereas above this concentration t1/2 was approximately constant and averaged 14.2 d. This implies that a conservation effect may be operative at low plasma vitamin C concentrations.

Adult↗

Reevaluation of the absorption of carbenoxolone using an in situ rat intestinal technique.

The absorption of the model drug carbenoxolone was reevaluated using an in situ rat intestinal perfusion technique in which disappearance from the intestinal lumen, binding to the perfused jejunal segment, and appearance in the mesenteric (jejunal) vein were measured. The effect of the degree of ionization on these processes was examined by employing perfusion solutions of pH 4.0, 4.4, 5.0, and 6.5. Tissue binding was observed to be independent of pH. There was a rank-order correlation of the transfer rate of carbenoxolone with the degree of ionization which indicated that carbenoxolone was absorbed faster in its ionized form. This observation is in direct opposition to the pH-partition hypothesis, a finding which appears to support the previous work of Bridges et al. Ion-pairing of carbenoxolone with sodium ion present in the pH 6.5 buffer is one possible explanation for the unusually high transfer rate seen at this pH. A more likely explanation is that at the low pH values, some carbenoxolone precipitated out of solution during the perfusion experiments, thereby reducing the driving force for diffusion across the intestinal wall.

Animals↗

Brachial plexus block with a new local anaesthetic: 0.5 per cent ropivacaine.

A new local anaesthetic, ropivacaine hydrochloride, was used in a concentration of 0.5 per cent in 32 patients receiving a subclavian perivascular block for upper extremity surgery. One group (n = 15) received 0.5 per cent ropivacaine without epinephrine and a second group (n = 17) received 0.5 per cent ropivacaine with epinephrine in a concentration of 1:200,000. Anaesthesia was achieved in 87 per cent of the patients in both groups in all of the C5 through T1 brachial plexus dermatomes. Motor block was profound with 100 per cent of patients in both groups developing paresis at both the shoulder and hand and 100 per cent developing paralysis at the shoulder. There was a rapid initial onset of sensory block (a mean of less than four minutes for analgesia) with a prolonged duration (a mean of greater than 13 hr of analgesia). The addition of epinephrine did not significantly affect the quality or onset of sensory or motor block. The duration of sensory block was reduced by epinephrine at T1 for analgesia and at C7, C8, and T1 for anaesthesia. The duration of sensory block in the remaining brachial plexus dermatomes as well as the duration of motor block was not effected by epinephrine. There was no evidence of cardiovascular or central nervous system toxicity in either group with a mean dose of 2.5-2.6 mg.kg-1 ropivacaine.

Adult↗

Plasma concentrations of ropivacaine given with or without epinephrine for brachial plexus block.

The purpose of this study was to determine the pharmacokinetic properties of the local anaesthetic ropivacaine used with or without epinephrine for brachial plexus block. Seventeen ASA physical status I or II adult patients undergoing elective orthopaedic surgery received a single injection of 33 ml ropivacaine for subclavian perivascular block and 5 ml to block the intercostobrachial nerve in the axilla. One group (n = 8) received 0.5 per cent ropivacaine without epinephrine (190 mg) and the other (n = 9) received 0.5 per cent ropivacaine with epinephrine 1:200,000 (190 mg). Plasma ropivacaine concentrations were measured from peripheral venous blood samples taken for 12 hr after drug administration. Ropivacaine base was determined in plasma using gas chromatography and a nitrogen-sensitive detector. The mean peak plasma concentration (Cmax) was 1.6 +/- 0.6 mg.L-1 and 1.3 +/- 0.4 mg.L-1 after administration of ropivacaine with and without epinephrine. The median time to peak plasma concentration (tmax) was 0.75 hr and 0.88 hr and the mean area under the plasma concentration curve AUC0-12h was 7.7 +/- 3.6 and 7.0 +/- 3.4 mg.l hr-1. The differences were not statistically significant. The terminal phase of the individual plasma concentration-time curves showed a varying and sometimes slow decline possibly indicating a sustained systemic uptake of ropivacaine from the brachial plexus. No central nervous system or cardiovascular symptoms attributed to systemic plasma concentrations of the drug were observed, with the dose (1.90-3.28 mg.kg-1) of ropivacaine used. It is concluded that the addition of epinephrine does not alter the pharmacokinetic properties of ropivacaine when used for subclavian perivascular brachial plexus block.

Adult↗

Intravenous regional sympatholysis: a double-blind comparison of guanethidine, reserpine, and normal saline.

This double-blind, randomized study was designed to compare the effectiveness of intravenous regional sympatholysis using guanethidine, reserpine and normal saline. Twenty-one patients with reflex sympathetic dystrophy of an upper or lower extremity were enrolled and received intravenous regional blockade (IVRB) with one of the three medications. There was significant pain relief in all three groups at 30 min. There were no significant differences among the three groups in the degree of pain relief, the number of patients obtaining pain relief in the 30 min after the block, or the number of patients reporting more than 50% pain relief for more than 24 hr. The saline group's high rate of pain relief could be partially due to a mechanism of tourniquet-induced analgesia.

Adult↗

Subarachnoid and epidural calcitonin in patients with pain due to metastatic cancer.

Nine patients with metastatic cancer who had pain refractory to traditional treatments received a subarachnoid injection of salmon calcitonin. Eight of the nine patients reported pain relief after subarachnoid injection varying from 1 hr to 5 days. Four of the responding patients subsequently received an epidural injection of salmon calcitonin, and two of these patients reported pain relief. Although many patients experienced pain relief, nausea and vomiting appeared to be a significant side effect, occurring in seven out of nine patients.

Analgesia, Epidural↗

Vitamin C disposition in young and elderly men.

The pharmacokinetics of vitamin C after a 500-mg oral tablet dose were compared in 15 healthy young men aged 25.20 +/- 2.54 (means +/- SD) and in 15 healthy elderly men aged 69.31 +/- 2.52 y. The doses were characterized with the subjects in two states of vitamin C nutriture: a depleted state, which was achieved by 4-5 wk of compliance with a vitamin C-restricted diet of less than 10 mg/d and a supplemented state, in which the subjects were given 500 mg vitamin C/d for 3 wk. Plasma and urine samples were collected for 72 h after the dose of vitamin C from depleted subjects and for 24 h from supplemented subjects and analyzed for vitamin C. Several of the pharmacokinetic indices measured were different in depleted vs supplemented subjects but none exhibited any age-related differences. This indicates that vitamin C nutriture affects vitamin C pharmacokinetics but age does not.

Administration, Oral↗

HPLC analysis of methylxanthines in human breast milk.

A sensitive and specific high-performance liquid chromatographic (HPLC) procedure is developed for simultaneously quantitating the levels of caffeine, theophylline, theobromine and paraxanthine in breast milk. The method involved the precipitation of proteins present in the milk samples with a 6% v/v perchloric acid solution containing the internal standard, proxyphylline, followed by centrifugation at 12,800 Xg for 10 minutes. The clear supernatant was then chromatographed on a C18 reversed-phase analytical column at ambient temperature using a wavelength of 272 nm. Samples were eluted from the column at a constant flow rate of 1.5 mL/min using a gradient program in which the concentration of methanol in the mobile phase varied from 0 to 16%. The mean recoveries of the methylxanthines averaged over all the concentrations examined were generally excellent and ranged from 96.3 +/- 5.4% for caffeine to 102.3 +/- 8.9% for paraxanthine. The assay precision was very good and the peaks of interest were extremely well resolved. The method is recommended for assessing the total caffeine and dimethylxanthine load to which the nursing infant is exposed in mothers ingesting typical amounts of caffeine.

Caffeine↗

A rapid and specific high-performance liquid chromatographic assay for theophylline in biological fluids.

A rapid, specific high-performance liquid chromatographic analysis of theophylline in plasma, serum, and saliva is described. Proteins present in the biological samples are precipitated with 6% perchloric acid and the clear supernatant is chromatographed on a reversed-phase column. Only 100 microL of serum is required and concentrations as low as 0.07 micrograms/mL can be measured accurately. Other xanthines do not interfere in the assay. Within- and between-day variation is less than or equal to 2.2%. The method shows less bias and greater precision than the TDx (Abbott Diagnostics) procedure commonly used in clinical laboratories.

Chromatography, High Pressure Liquid↗

Comparison of methods for estimating body composition in young and elderly women.

Estimates of percent body fat and fat-free mass (FFM) were made in healthy young and elderly female subjects using five different methods: bioelectrical impedance analysis (BIA); regression equations involving skinfold measurements at two (Durnin and Womersley; SKF-DW) or three (Jackson and Pollack; SKF-JP) sites; the body mass index (BMI); and an equation relating height and weight to total body water (TBW). Three of the five methods indicated that the percent body fat was significantly greater in the elderly age group. Similarly, three methods estimated FFM values that were significantly lower in the elderly group. In the young group the SKF-DW and TBW methods produced percent fat estimates significantly higher than the other three methods. In the elderly group the percent fat estimates were as follows: SKF-DW greater than BIA greater than SKF-JP = TBW greater than BMI. FFM estimates in both age groups were in inverse rank order to the percent fat estimates. In elderly subjects SKF-DW produced results closest to those from BIA, whereas in young subjects SKF-JP provided the best agreement with the BIA procedure.

Adipose Tissue↗

Comparison of ultrafiltration devices for assessing theophylline protein binding.

The ability of two commercially available ultrafiltration devices to assess the protein binding of theophylline was compared using human serum albumin in pH 7.4 buffer at 37 degrees C. The devices compared were the Millipore-MC filter units (Catalog number UFC3LGC00) and the Amicon Centrifree Micropartition System; both rely on centrifugal force to separate the unbound and bound molecules. The results from each device were essentially identical provided that the Millipore units were centrifuged using conditions that would not allow heat buildup to occur and thereby cause a decrease in the binding. This problem could be minimized if the Millipore units were available in a low-binding 30,000 dalton cutoff membrane instead of the 10,000 dalton membrane currently available. The use of the Millipore 30,000 dalton cutoff polysulfone membrane (UFC3TTK00) reduced the centrifugation time necessary to obtain a sufficient volume of ultrafiltrate for assay, thereby minimizing the possibility of heat generation. Furthermore, the binding of theophylline to this device was low and comparable to the binding to the Centrifree devices. Because this low degree of membrane binding may not hold for other drugs, we would suggest that a Millipore unit supplied with a low-binding, 30,000 dalton cutoff membrane could provide binding data with an efficacy comparable to that achieved with the Centrifree devices.

Humans↗

Experimental infection of timed-pregnant rhesus monkeys with simian immunodeficiency virus (SIV) during early, middle, and late gestation.

Ten rhesus monkeys were inoculated with SIV/DeltaB670 during various stages of gestation to determine factors predictive of transplacental infection. Two abortions associated with rapid disease occurred shortly after infection; uninfected infants were caesarean delivered from eight other females. SIV-specific RNA accompanied by deciduitis was identified in the maternal portion of two placentas suggesting that opportunistic infections may promote entry of SIV into placental tissue. The lack of evidence for SIV infection of caesarean delivered infants suggests that fetal infection may often occur during parturition.

Abortion, Spontaneous↗

[Sarcoid reaction to a foreign body located in the uterus and the liver].

A case is reported of a sarcoidosis reaction within the uterine wall which developed following the vaginal injection of an unknown substance for contraceptive purposes. The reaction spread through the body to affect the lymphnodes and liver. Can this serve as an experimental model for the various forms of sarcoidosis observed clinically, notably genital sarcoidosis?

Female↗