Addition of grape seed extract and bearberry to porcine diets: Influence on quality attributes of raw and cooked pork.

The effect of supplementation of pig diets with grape seed extract (GSE) (100, 300, 700mg/kg feed) and bearberry (BB) (100, 300, 700mg/kg feed) for 56 days pre-slaughter, on the oxidative stability and quality of raw and cooked M. longissimus dorsi (LD) was examined. Susceptibility of porcine liver, kidney and heart tissue homogenates to iron-induced (1mM FeSO(4)) lipid oxidation was also investigated. In raw LD steaks, stored in modified atmosphere packs (75% O(2):25% CO(2)) (MAP) for up to 16 days at 4°C, surface lightness (CIE 'L' value), redness (CIE 'a' value), lipid stability (TBARS, mg MDA (malondialdehyde)/kg muscle) and pH were not significantly affected by supplemental GSE or BB. Similarly, the oxidative stability and sensory properties of cooked LD steaks, stored in MAP (70% N(2):30% CO(2)), for up to 28 days at 4°C, were not enhanced by dietary GSE or BB. Iron-induced lipid oxidation increased in liver, kidney and heart tissue homogenates over the 24h storage period and susceptibility to oxidation followed the order: liver>heart>kidney. Dietary GSE or BB did not significantly reduce lipid oxidation in tissue homogenates. Potential reasons for the lack of efficacy of supplemental GSE and BB on pork quality were explored.

Effects of plasmid-mediated growth hormone releasing hormone supplementation in young, healthy Beagle dogs.

Our study focused on the evaluation of the pharmacological and toxicological effects of plasmid-mediated GHRH supplementation with electroporation in normal adult dogs over a 180-d period. Twenty-eight dogs (< 2 yr of age) were randomized to four groups. Three groups (four dogs/sex for each group) were treated with ascending doses of GHRH-expressing plasmid: 0.2, 0.6, and 1 mg. One group (two dogs of each sex) served as the control. Clinical observations and body weights were recorded. Hematological, serum biochemical, and urine analyses were performed. Serum IGF-I, ACTH, and insulin were determined. Necropsies were performed on d 93 and 180; organs were weighed and tissues were fixed and processed for light microscopy. Selected tissues were used to assess plasmid biodistribution on d 93. At all doses, plasmid GHRH caused increased weight gain (P < 0.001), without organomegaly. Serum glucose and insulin in fasted dogs remained within normal ranges at all time points. Adrenocorticotropic hormone was normal in all groups. Significant increases in number of red blood cells, hematocrit, and hemoglobin (P < 0.01) were observed. In conclusion, our study shows that plasmid-mediated GHRH supplementation is safe in electroporated doses up to 1.0 mg in young healthy dogs.

Randomized double-blind study of the clinical duration and efficacy of Nesacaine-MPF 2% and 3% in peribulbar anesthesia.

PURPOSE: To compare 2 commercially available concentrations of Nesacaine-MPF (2-chloroprocaine) to determine the time to onset of adequate motor blockade, the quality of surgical anesthesia, and the duration of motor blockade in the extraocular muscles after peribulbar anesthesia for cataract surgery. SETTING: Tampa Eye and Specialty Surgery Center, Tampa, Florida, USA. METHODS: This double-blind, randomized, single-center study comprised 40 patients scheduled to receive peribulbar anesthesia before cataract surgery. Patients were given 5 mL of Nesacaine-MPF 2% or 3% before surgery. Beginning at the end of the injection, assessments of ocular and eyelid movement were made every 2 minutes until adequate motor blockade was achieved or 25 minutes elapsed. Ocular assessments were made immediately after completion of surgery, 60 minutes after the end of the initial injection, and at 15 minute intervals thereafter until full recovery. Assessments of the quality of anesthesia achieved by the patient during surgery were made by the surgeon. RESULTS: The 3% solution provided significantly faster onset of surgical anesthesia than the 2% solution (mean 3.9 minutes +/- 2.2 [SD] versus 6.0 +/- 3.6 minutes) (P = .02) but also required more time for recovery from anesthesia (98.9 +/- 18.7 minutes versus 84.8 +/- 20.6 minutes) (P = .02). All patients had adequate surgical anesthesia. Duration of ocular motor function was brief enough so that all patients could be sent home without an eye patch. Both concentrations were safe for use in this procedure. CONCLUSION: Both Nesacaine-MPF 2% and 3% produced safe and effective peribulbar anesthesia in all patients; however, the 3% solution provided better duration of clinical anesthesia.

Long-term neurodevelopmental outcome after intrauterine transfusion for the treatment of fetal hemolytic disease.

OBJECTIVE: The aim of the study was to assess the developmental outcome of neonatal survivors of hemolytic disease of the neonate treated with modern intrauterine transfusion techniques. STUDY DESIGN: In this prospective, observational study, auditory evoked-response tests were performed in the nursery. Neurodevelopmental evaluation with the Gesell Developmental Schedules was performed between 9 and 18 months of corrected age to assess motor skills, language development, comprehension capacity, and social skills. The McCarthy Scales of Children's Abilities were administered between 36 and 62 months. RESULTS: Forty children who survived severe fetal hemolytic disease were followed up until 62 months old. Demographic data included gestational age at first intrauterine transfusion (26.4 +/- 3.7 weeks), median number of intrauterine transfusions (4, range 1-8), lowest fetal hematocrit (20.2% +/- 7.8%), peak fetal bilirubin (7.1 +/- 2.1 mg/dL), incidence of hydrops fetalis (45%), and mean gestational age at delivery (35.6 +/- 2.2 weeks). One case of severe bilateral deafness and 1 case of right spastic hemiplegia were diagnosed. The Gesell Developmental Schedules score was assessed between 9 and 18 months of corrected age in 22 infants. The global developmental quotient was 101.9 +/- 9.5 (mean for normal population is 100). Regression analysis revealed no correlation between the global developmental quotient and gestational age at the first intrauterine transfusion, gestational age at birth, or the severity of the fetal hemolytic disease (fetal hematocrit, fetal bilirubin, presence of hydrops fetalis, total number of intrauterine transfusions, duration of neonatal phototherapy, and number of neonatal exchange transfusions). Eleven of the 40 children were followed up until they were 62 months old, and the McCarthy Scales of Children's Abilities were administered. The mean cognitive index was 107.6 +/- 9.4 (90-109 is considered average). CONCLUSION: Despite severe fetal hemolytic disease, normal developmental outcome can be expected for children treated with intrauterine transfusions.

A proposed approach to study the toxicology of complex mixtures of petroleum products: the integrated use of QSAR, lumping analysis and PBPK/PD modeling.

Mixture toxicity is a topic that has become a matter of concern during the last two decades. One of the major problems with assessing the toxicity of mixtures and the associated human and environmental risk is the large number of possible mixtures, as well as the fact that the actual mixture effect for a given set of constituents might strongly depend on the actual composition of the mixture, i.e., the ratios of the constituent, as well as their nature. This paper presents a possible approach to describe and thereby better understand the pharmacokinetics and dynamics of complex mixtures by combining quantitative structure-activity relationships to predict needed parameters, lumping to reduce the complexity of the problem, and physiologically based pharmacokinetic/pharmacodynamic modeling to integrate all this information into a complete toxicological description of the mixture. It is our hope that by presenting this conceptual approach we might be able to stimulate some criticisms and discussions in the toxicology community regarding this complex and yet very important area of research.

The peripheral nerve stimulator: a monitor during continuous spinal anesthesia. Case report.

BACKGROUND AND OBJECTIVES: A continuous spinal anesthetic was planned and conducted for a medically compromised and demented 80-year-old man presenting for repair of an intratrochanteric hip fracture. METHODS: A peripheral nerve stimulator was successfully employed to monitor the height and to help time the redosing of the continuous spinal anesthetic. RESULTS: The use of a peripheral nerve stimulator allowed careful titration of our continuous spinal anesthetic to provide dense analgesia at the surgical site for 1 hour 5 minutes, using a total spinal dose of 27 mg lidocaine and 7.5 micrograms spinal fentanyl. CONCLUSION: A standard peripheral nerve stimulator is an effective monitor to help optimize management of continuous spinal anesthesia.

Family structure, neonatal infection, and hay fever in adolescence.

OBJECTIVE: To determine whether increased numbers of siblings and infection in early life protect against allergic sensitisation. DESIGN: Historical cohort study. SETTING: Sheffield, UK. SUBJECTS: 11,765 children aged 11-16 years for whom a history of neonatal infectious illness had been recorded systematically at 1 month of age. METHODS: A history of hay fever and family structure was obtained by postal questionnaire; neonatal illness history was ascertained from health visitor records; 723 children underwent skin prick testing with mixed grass pollen extract. RESULTS: The prevalence of hay fever was reduced (p < 0.0001) among children of younger mothers, and those from larger families. The number of older siblings exerted a stronger independent effect than the number of younger siblings (p < 0.001). Infants breast fed exclusively during the first month were at higher risk (p < 0.05) of subsequent hay fever, independent of demographic factors. Adolescents at high risk of hay fever by virtue of their family structure were more likely to be sensitised to grass pollen (p < 0.002). No significant relations emerged between hay fever and infection in the first month of life, even among children born in June. CONCLUSIONS: The association of hay fever with family structure is not due to reporting bias and reflects an environmental influence on allergic sensitisation. The effects of sibship size, birth order, and infant feeding are consistent with a protective influence of postnatal infection. The first month of life and the first postnatal exposure to allergen are not the critical periods during which this protective effect is determined.

The effects of electrical stimulation at different frequencies on perception and pain in human volunteers: epidural versus intravenous administration of fentanyl.

The study was performed to determine whether epidural fentanyl produced segmental sensory changes to electrical stimulation at different frequencies. Eight healthy volunteers received fentanyl 1 microgram/kg both intravenously and epidurally in a randomized, double-blind, cross-over fashion. Perception thresholds and amount of current required to elicit a predetermined level of moderate pain (Cmp) at 5,250, and 2000 Hz stimulation were measured at ipsilateral dermatomes C2 and L2 at 0, 5, 15, 30, 45, and 60 min after injection. Perceptions to 5,250, and 2000 Hz stimulation were unaffected by either intravenous or epidural fentanyl (P > 0.08). Intravenous fentanyl increased Cmp at both 5 and 250 Hz at both dermatomes (P < 0.004) and thus did not produce segmental analgesia. In contrast, epidural fentanyl increased Cmp only at the L2 dermatome and only at 5 Hz (P = 0.005). We conclude that an epidural bolus of fentanyl results in segmental spinal analgesia to transcutaneous electrical stimulation only at specific frequencies. Furthermore, pain produced by stimulation at 5 Hz may have a different pharmacology than pain produced by 250 Hz stimulation.

Epinephrine prolongs duration of subcutaneous infiltration of local anesthesia in a dose-related manner. Correlation with magnitude of vasoconstriction.

BACKGROUND AND OBJECTIVES: Epinephrine is frequently combined with local anesthesia to prolong analgesia. Determination of the minimal concentration and the dose of epinephrine that produces prolongation of analgesia is important in the face of epinephrine's potential for systemic and local toxicity. The authors undertook this study to determine a dose-response curve of epinephrine on duration of analgesia of both 1% lidocaine and 0.25% bupivacaine after local infiltration. In order to determine whether epinephrine-induced vasoconstriction affected duration of analgesia, the authors correlated duration of analgesia with magnitude of local vasoconstriction as measured with laser Doppler flowmetry. METHODS: Six volunteers were studied in a randomized double-blind manner. Ten skin wheals of 0.2 mL solution were subcutaneously injected into both forearms of each volunteer. The solutions consisted of 1% lidocaine with epinephrine concentrations of 0, 1:50,000, 1:200,000, 1:800,000, and 1:3,200,000, and 0.25% bupivacaine with the same epinephrine concentrations. Duration of loss of sensation to pinprick at each wheal was recorded. Skin wheals with 0.2 mL of these same solutions were also subcutaneously injected into the abdomen of the same 6 volunteers, and laser Doppler flowmetry readings of skin blood flow were measured for 6 hours after injection. RESULTS: Epinephrine prolonged duration of analgesia for both lidocaine and bupivacaine in a dose-related manner (P < .001). All concentrations of epinephrine attenuated the vasodilation observed in the first 15 minutes after injection with plain local anesthesia (P = .03), and blood flow returned to baseline by 30 minutes after injection of either plain or epinephrine-containing solutions. Duration of analgesia correlated with magnitude of vasoconstriction only at the 15-minute measurement (r = .53 and .57, P = .003 and 0.001 for lidocaine and bupivacaine, respectively). CONCLUSIONS: Epinephrine prolongs duration of analgesia after local infiltration in a dose-related manner. Addition of epinephrine in concentrations of 1:50,000 or 1:200,000 increases duration of analgesia after local infiltration by approximately 200%. Addition of doses as dilute as 1:3,200,000 still increases duration of analgesia by approximately 100%. Duration of analgesia appears to correlate with magnitude of epinephrine-induced vasoconstriction using laser Doppler flowmetry. Based on study data, the use of epinephrine in concentrations from 1:200,000 to 1:3,200,000 is recommended for prolongation of analgesia after local infiltration.

Perioperative pain management.

The clinical anesthesia, general surgery, and gynecology literature addressing the pathophysiology and management strategies for perioperative pain were reviewed. There are few prospective, randomized studies from which to draw meaningful conclusions. Nevertheless, a theoretical construct has been developed which may help the gynecologic surgeon optimizing pain management. The era of managed care and shorter hospital stays has focused physicians and, in particular, surgeons on elements of patient care that can be addressed and improved. Reducing or eliminating postoperative pain without excessive sedation promotes rapid mobilization and return to self-care. Strategies for pain management can be adopted that reduce postoperative ileus and other adverse reactions to analgesics.

The use of nimodipine in a patient with eclampsia: color flow Doppler demonstration of retinal artery relaxation.

Color flow Doppler ultrasonography was used to demonstrate a significant and sustained reduction in the central retinal artery pulsatility index after administration of the calcium antagonist nimodipine to a patient with eclampsia. Nimodipine is an effective cerebral vasodilator and may be useful in the management of eclamptic patients with severe vasospasm.

Toxicologic evaluation of injectable acemannan in the mouse, rat and dog.

Acemannan, the USAN-accepted name for long-chain polydispersed beta-(1,4)-acetylated polymannose with interspersed 0-acetyl groups with a mannose monomer/acetyl ratio of approximately 1:1 and extracted from Aloe vera (barbadensis Miller), was administered as a 1.0 mg/ml solution to mice, rats and dogs, either as single dose or repeated at 4-d intervals for 8 doses by iv or ip routes. No significant signs of intoxication and no deaths occurred in animals treated with the single injection of acemannan at dosages of 80 mg/kg iv or 200 mg/kg ip in mice, 15 mg/kg iv or 50 mg/kg ip in rats, and 10 mg/kg iv or 50 mg/kg ip in dogs. On repeated injections systemic toxicity was limited to obvious transient discomfort that appeared dose related. There was accumulation of macrophages and monocytes without subsequent inflammatory reaction in lungs of the iv-treated animals, and in liver and spleen and on peritoneal surfaces of ip-treated animals. The effects were not considered adverse, but were consistent with the known immune stimulating activity of acemannan. A few deaths occurred in mice and rats that were suggestive of resulting from improper injection or sequella of necrosis of the injection site. The NOAELs for acemannan determined from these repeated injection studies were 20 mg/kg iv or ip in the mouse, 4.0 mg/kg iv and 50 mg/kg ip in the rat, and 1.0 mg/kg iv in dogs; 5.0 mg acemannan/kg ip in the dog was considered to be LOAEL, based on the emesis and abdominal discomfort induced.

In vitro evaluation of the synergistic antiviral effects of acemannan in combination with azidothymidine and acyclovir.

The antiviral effects of selected combinations between acemannan (ACE-M), a long-chained, polydispersed, beta-(1,4)-acetylated mannan, were tested in combination with azidothymidine (AZT) and acyclovir (ACY) in vitro. The rationale for such combinations was based on the antiviral and immunomodulatory properties exhibited by ACE-M. In addition, the observed antiviral effects of ACE-M against human immunodeficiency virus type 1 (HIV-1) and other enveloped viruses appear to be related to modification of the glycosylation of viral glycoproteins. Therefore, the inhibitory effect of ACE-M does not overlap with that of AZT or ACY. The studies presented herein show that ACE-M combined with suboptimal noncytotoxic concentrations of AZT or ACY act synergistically to inhibit the replication of HIV-1 and herpes simplex virus type 1 (HSV-1), respectively. The median effect method was not applicable for analysis because the test compounds show mutually nonexclusive drug effects. For a meaningful evaluation and interpretation of the effects of drug combinations, the biological significance of combinations must be considered, that is, the protective effect of the combination, the noncytotoxicity of the combination, the mechanism(s) of action of the individual compounds comprising the combination, and so forth. With respect to effects on U1 cells latently infected with HIV-1, treatment with combinations of AZT and ACE-M does not potentiate virus replication.

A comparison of conductivity-based hematocrit determinations with conventional laboratory methods in autologous blood transfusions.

An investigation was made of the accuracy of a portable hematocrit measurement device (Stat-Crit) on the infusate of an autologous blood transfusion system. Baseline hematocrit values were determined by three methods on in vivo blood samples of surgical patients immediately after the start of surgery, and again on the first product of the autologous blood retrieval system. At baseline, there were no significant differences in the values determined by the Stat-Crit (33.4% +/- 6.2%, mean +/- SD) and those determined by the microcentrifuge technique (33.8% +/- 4.7%) or by the Coulter method (33.5% +/- 4.5%) (P = 0.9). In contrast, hematocrit values determined on infusate samples by the Stat-Crit (36.6% +/- 4.8%) were significantly lower than those determined by the microcentrifuge technique (51.2% +/- 5.9%) or by the Coulter method (51.6% +/- 5.8%) (P = 0.0001). This study confirms close agreement of hematocrit values derived by the conductivity of whole blood in normal samples with those determined by conventional laboratory techniques, but indicates that this method will report falsely low readings in situations where plasma has been replaced by crystalloid, as in patients who have received large transfusions of processed autologous blood.

Serial maternal blood donations for intrauterine transfusion.

Because of concern regarding viral disease transmission, 21 pregnant women who had been alloimmunized to various red-cell antigens donated 77 units of blood (range two to six donations) for intrauterine transfusion to their anemic fetuses. Patients received supplemental iron and vitamin therapy throughout the blood donation period. Before the first donation, the mean (+/- SD) maternal hematocrit was 34.4 +/- 2.8%, whereas at delivery it was 33.4 +/- 3.5%. Maternal hematocrit was noted to decline slightly between the first and second donations but returned to pre-donation values with subsequent donations. No adverse maternal or fetal effects occurred secondary to repeated donations. Use of maternal designated-donor red cells for intrauterine transfusion offers potential advantages over the use of random allogeneic red blood cell units.

Intravenous pancuronium bromide for fetal neuromuscular blockade during intrauterine transfusion for red-cell alloimmunization.

Intravenous pancuronium bromide was administered into the umbilical cord by funipuncture to effect temporary fetal paralysis. Neuromuscular blockade was achieved in 12 fetuses undergoing a total of 34 intrauterine procedures for the treatment of severe red-cell alloimmunization. The same initial dose of 0.2 mg/kg fetal weight estimated by ultrasound was used in all cases, but anemic fetuses did not resume movement for prolonged periods. A relationship among fetal hematocrit, adjusted dose, and duration of paralysis was described by the equation: Duration (hours) = 5.24 + 10.30 adjusted dose (mg/kg) - 0.16 hematocrit (%) (R2 = 0.49; P less than .001). Intravenous pancuronium was found to be a safe and effective method for cessation of fetal movement during intrauterine procedures.

The use of fetal neuromuscular blockade during intrauterine procedures.

Advances in fetal therapy have led to the utilization of such techniques as intravascular transfusion of the Rh-affected fetus, bladder shunt placement in the fetus with obstructive uropathy, and percutaneous umbilical blood sampling. Fetal movement makes these procedures technically more difficult while increasing the risk of fetal injury. However, maternal sedation rarely results in adequate suppression of fetal activity. Thus we tested the sedative effects of intramuscular d-tubocurarine (3 or 1.5 mg/kg) or pancuronium bromide (0.3 mg/kg) injected into the fetal gluteal region under ultrasound guidance in conjunction with 70 invasive in utero procedures. Short-term paralysis of the fetus was induced in all cases. No deleterious effects of this technique were noted on initial examination of the neonates. Neuromuscular blockade was found to be a very useful adjunct to both diagnostic and therapeutic procedures involving the fetus.