Comparative physiological pharmacokinetics of fentanyl and alfentanil in rats and humans based on parametric single-tissue models

The objectives of this investigation were to characterize the disposition of fentanyl and alfentanil in 14 tissues in the rat, and to create physiological pharmacokinetic models for these opioids that would be scalable to man. We first created a parametric submodel for the disposition of either drug in each tissue and then assembled these submodels into whole-body models. The disposition of fentanyl and alfentanil in the heart and brain and of fentanyl in the lungs could be described by perfusion-limited 1-compartment models. The disposition of both opioids in all other examined tissues was characterized by 2- or 3-compartment models. From these models, the extraction ratios of the opioids in the various tissues could be calculated, confirming the generally lower extraction of alfentanil as compared to fentanyl. Assembly of the single-tissue models resulted in a whole-body model for fentanyl that accurately described its disposition in the rat. A similar assembly of the tissue models for alfentanil revealed non-first-order elimination kinetics that were not apparent in the blood concentration data. Michaelis-Menten parameters for the hepatic metabolism of alfentanil were determined by iterative optimization of the entire model. The parametric models were finally scaled to describe the disposition of fentanyl and alfentanil in humans. Supported in part by the National Institute on Aging, RO1-AG-4594, and the Anesthesia/Pharmacology Research Foundation.     

Intensity-dependent regional cerebral blood flow during 1-Hz repetitive transcranial magnetic stimulation (rTMS) in healthy volunteers studied with H215O positron emission tomography: II. Effects of prefrontal cortex rTMS.

BACKGROUND: The changes in brain activity produced by repetitive transcranial magnetic stimulation (rTMS) of the prefrontal cortex (PFC) remain unclear. We examined intensity-related changes in brain activity with positron emission tomography (PET) in normal volunteers during rTMS delivered to the left PFC. METHODS: In 10 healthy volunteers, we delivered 1-Hz rTMS at randomized intensities over left PFC with a figure-eight coil. Intensities were 80, 90, 100, 110, and 120% of the right-hand muscle twitch threshold. Regional cerebral blood flow (rCBF) scans were acquired with H(2)(15)O PET during rTMS at each intensity. RESULTS: Repetitive transcranial magnetic stimulation intensity was inversely correlated with rCBF in the stimulated and contralateral PFC, ipsilateral medial temporal lobe, both parahippocampi, and posterior middle temporal gyri. Positive correlations of rCBF with intensity occurred in ipsilateral anterior cingulate, cerebellum, contralateral insula, primary auditory cortex, and somatosensory face area. CONCLUSIONS: The intensity-related inverse relationship between 1-Hz rTMS and prefrontal activity appears opposite to that seen with rTMS over the motor cortex in a companion study. Intensity-dependent increases in rCBF were seen in a number of distant cortical and subcortical areas with PFC rTMS, suggesting activation of left anterior cingulate, claustrum, and cerebellum. The regional differences in direction of rTMS effects and the greater activation of distant structures at higher intensities suggest the potential importance of higher-intensity prefrontal rTMS for therapeutic applications in neuropsychiatric patients.     

The Role and Value of a Paediatric Specialist Neurodevelopmental Diagnostic Service: Parental Perceptions

Background:  This study was undertaken to explore parental perceptions of the role and value of a specialist service for children and families. This service offers assessment and diagnosis of children with neurodevelopmental disorders of the kind that are not evident at birth.
Method:  Information was collected from 37 families on expectations and experience of clinic attendance, user satisfaction and outcome through interviews and questionnaires, once before and twice after clinic attendance.
Results:  87% of parents found clinic attendance worthwhile, with most expecting to be provided with a diagnosis and advice on education. Parents perceived that the clinic was best able to meet their diagnostic needs and they reported that they were more able to obtain a diagnosis and a specialist opinion at a regional centre than at local clinics. Parent satisfaction with the parent-child relationship improved following clinic attendance and parents' self-identified concerns about their child decreased.     

Femoral and lateral femoral cutaneous nerve block for muscle biopsies in children

Retrospective chart review (1978–1993) of 179 children less than age 18 (10.0 ± 3.8 SD yrs) undergoing muscle biopsy for determination of susceptibility to malignant hyperthermia provided data. One hundred and forty-six patients received femoral and lateral femoral cutaneous nerve blocks as their primary anaesthetic. We examined age, weight, duration of surgery, time to discharge from hospital, choice and dosage of local anaesthetics, choice and dosage of sedation, postoperative pain medications, and complications. All children receiving this form of anaesthesia remained outpatients. Between 1978 and 1985 procaine (10 mg·kg^-1) with hyaluronidase or 2-chloroprocaine (12 mg·kg^-1) provided nerve blockade; after 1985, lignocaine (6.8 mg·kg^-1), or a combination of lignocaine or mepivacaine and 2-chloroprocaine, were the preferred agents. More recently the combination of 2-chloroprocaine and bupivacaine has been popular. Three patients required admission to the recovery room postoperatively, due to heavy sedation. Forty-three children (29%) received pain medication during recovery. Femoral and lateral femoral cutaneous block anaesthesia with light to moderate sedation is well tolerated in children undergoing anterior thigh procedures.     

脑血管病大脑局部血流量变化研究

本文对122例脑血管病人进行~(133)XE吸入法大脑局部血流量检查,研究脑梗塞及脑出血时脑局部血流量的变化,表现为脑血管病变部位局部血流量减少,并且变化范围较CT改变广泛,能在脑实质发生形态改变前测定出脑循环的改变。但无助于脑缺血与脑出血的鉴别诊断。     

Quantitative measurement of regional lung ventilation using 3He MRI.

A new strategy for a quantitative measurement of regional pulmonary ventilation using hyperpolarized helium-3 (3He) MRI has been developed. The method employs the build-up of the signal intensity after a variable number of (3)He breaths. A mathematical model of the signal dynamics is presented, from which the local ventilation, defined as the fraction of gas exchanged per breath within a given volume, is calculated. The model was used to create ventilation maps of coronal slices of guinea pig lungs. Ventilation values very close to 1 were found in the trachea and the major airways. In the lung parenchyma, regions adjacent to the hilum showed values of 0.6-0.8, whereas 0.2-0.4 was measured in peripheral regions. Monte Carlo simulations were used to investigate the accuracy of the method and its limitations. The simulations revealed that, at presently attainable signal-to-noise ratios, the ventilation parameter can be determined with a relative uncertainty of <5% over a wide range of values.     

Regional Differences in Norepinephrine and Dopamine Concentration and Effect on Serotonin Uptake and Release in Bovine Pineal Gland

In order to analyze whether the bovine pineal gland is a homogeneous or a heterogeneous structure as far as monoamine content, the regional differences in norepinephrine (NE), dopamine (DA), serotonin (5HT), and 5-hydroxyindoleacetic acid (5HIAA) contents were assessed by high-pressure liquid chromatography. NE content was maximal in the proximal (close to the recessus pinealis) region and decreased in a rostral-caudal direction to achieve minimal values at the distal region. DA exhibited an opposite trend to NE, NE/DA ratios varying from 3.2 (proximal region) to 1.4 (distal region). Significantly lower NE content was found at the inferior as compared to the superior pineal region, and at the cortex as compared to the medulla. No significant differences were detected in DA concentration of these latter pineal regions, or in 5HT or 5HIAA concentration as a function of the region examined. 3H-5HT and 3H-NE uptake were maximal at the proximal zone in a rostral-caudal direction, at the superior as compared to the inferior region, and at the medulla as compared to the cortex. Unlabeled NE was equally effective to compete with 3H-5HT uptake in the several pineal regions studied. While NE increased maximally 3H-5HT release in a rostral-caudal direction, DA exhibited an opposite trend, displaying maximal 5HT release activity at the distal pineal region. DA and NE 5HT-releasing activity were greater in the pineal medulla than in the cortex, and did not exhibit differences in the superior as compared to the inferior pineal aspects. Excess (55 mM) K+ released 3H-5HT to a similar extent regardless of the pineal region examined.     

Ropivacaine in peribulbar block: a comparative study with bupivacaine

BACKGROUND: Ropivacaine is a new local anesthetic with alleged lower systemic toxicity and slightly lower potency as compared with bupivacaine. The present study aimed to evaluate the efficacy of ropivacaine in peribulbar block, as compared with that of bupivacaine. METHODS: Eighty patients aged 45-92 years with physical status ASA I, II, or III were randomized to Group R (n=40) or Group B (n=40). Group R received 8.0 ml of 1.0% ropivacaine and Group B received 8.0 ml of 0.75% bupivacaine, both solutions with 50 IU/ml hyaluronidase, to induce peribulbar block according to the double-injection technique. Decreased ocular motility was the only criterion of successful block. RESULTS: The percentage of patients with decreased ocular motility showing successful block was higher in Group R 1 and 5 min after injection. A score indicating successful peribulbar block was found in all patients 10 min after injection. While no patient complained of a burning sensation during ropivacaine injection, 22.5% of the patients given bupivacaine reported this symptom. CONCLUSION: Both local anesthetics were effective in inducing peribulbar block for intraocular surgery. A tendency was noted to a faster onset of peribulbar block with ropivacaine; nevertheless, both drugs had a high degree of success for this block.