A randomized clinical trial of the effectiveness of a scheduled oral analgesic dosing regimen for the management of postoperative pain in children following tonsillectomy

The purpose of this study was to determine whether around-the-clock (i.e. ATC) dosing of acetaminophen with codeine, with or without nurse coaching, compared to standard care with as needed (i.e. PRN) dosing: reduced children's reports of pain intensity with and without swallowing; increased pain relief, and increased analgesic consumption. Eighty children, 6-15 years, undergoing tonsillectomy were randomized to one of three treatment groups to receive acetaminophen with codeine (120 mg/12 mg/5 ml) for 3 days after surgery: PRN group (N = 28)-every 4 h PRN, with standard postoperative instructions, without nurse coaching; ATC group (N = 26)-every 4 h ATC, with standard postoperative instructions, without nurse coaching; and ATC+coaching group (N = 26)-every 4 h ATC, with standard postoperative instructions and nurse coaching. In all three groups, significant decreases were found over time in pain intensity scores at rest (P < 0.001) and with swallowing (P < 0.001). However, mean pain scores at rest and with swallowing were >3/10 until the fourth evening after tonsillectomy. Children in both ATC dosing groups received significantly greater amounts of acetaminophen and codeine than children in the PRN group (P < 0.003). No significant differences were found in the amount of analgesic administered between the ATC dosing groups with and without nurse coaching. No significant differences were found in the amount of nausea and vomiting among the three groups. Scheduled dosing of acetaminophen with codeine did not provide adequate pain relief for children following tonsillectomy. Nurse coaching does not increase parent's adherence with an ATC dosing schedule.     

The anti-thyroid drug methimazole induces neovascularization in the neonatal rat analogous to ROP

PURPOSE: To determine the effect of methimazole (MMI), an anti-thyroid drug known to reduce serum l-thyroxine (T4), and insulin-like growth factor (IGF)-1 concentrations, on retinal vascular development in neonatal rats. METHODS: Sprague-Dawley rats (n=175) were raised in expanded litters of 25 in room air and were exposed to MMI from birth (given as a 0.1% solution to nursing mothers for either 4 or 10 days). Experiments ended on day 4 (n=25) or 10 (n=50) of life. A third group was exposed to MMI for the initial 4 days of life and then allowed to recover for the next 6 days (n=50). Fifty control rats were analyzed on day 4 (n=25) or 10 (n=25) of life. Left eyes were fixed, and retinas were dissected and stained with adenosine diphosphatase (ADPase). Retinas were graded for presence and severity of neovascularization (NV) in a masked manner, and retinal vascular areas were quantified. In a subsequent study, serum IGF-1 and T4 levels were measured by radioimmunoassay in an additional 200 rats exposed to treatments identical to those described. RESULTS: Retinal NV occurred in 31% of rats exposed to 10 days of MMI and 4% (P=0.02) of rats exposed to 4 days of MMI, followed by 6 days of recovery. None of the rats exposed to 4 days of MMI alone and none of the control animals was graded positive for NV. Retinal vascular areas were significantly reduced in rats exposed to 4 days of MMI compared with 4-day control animals (36% +/- 6% vs. 50% +/- 6%, P=0.0001). Serum IGF-1 levels were markedly reduced in 4-day MMI rats compared with age-matched control animals (42 ng/mL vs. 133 ng/mL, P=0.0001) and in 10-day MMI rats compared with 10-day control animals (133 ng/mL vs. 206.5 ng/mL, P=0.005). Serum T4 levels were similarly suppressed in the MMI-exposed litters compared with control animals at day 10 (P=0.008). In contrast, rats exposed to 4 days of MMI followed by 6 days of recovery had normal serum IGF-1 and T4 levels by day 10. CONCLUSIONS: The anti-thyroid drug, MMI, induces NV in neonatal rats. This may be mediated by the initial suppression of serum IGF-1. Nevertheless, the lower incidence of NV when serum IGF-1 levels are initially suppressed followed by complete recovery, is contrary to a purely permissive role for serum IGF-1, as reported previously. The relationship between the temporal course of serum IGF-1 and NV in immature retinas needs further investigation.     

Changing immunodominance patterns in antiviral CD8 T-cell responses after loss of epitope presentation or chronic antigenic stimulation

The H-2(b)-restricted CD8 T-cell response against lymphocytic choriomeningitis virus is directed against at least 10 dominant and subdominant epitopes, including two newly identified epitopes in the nucleoprotein. We have used this set of epitopes to characterize the plasticity of the hierarchy under different experimental circumstances, i.e., loss of MHC class I molecules, loss of specific epitopes (CTL escape), and prolonged antigenic stimulation (chronic infection). We found that loss of epitope-specific responses was almost inevitably associated with compensatory responses against other, subdominant, epitopes. Multiple epitope loss was required to change the hierarchy. Persistent viral infection was associated with a loss of not only the dominant response against the NP396 epitope, but also a loss of subdominant responses against nucleoprotein epitopes. In contrast, responses against glycoprotein epitopes, dominant and subdominant, survived under chronic infection conditions, and even dominated the response (GP118). Our results suggest that the fate of each specific T-cell response during chronic infection is in part determined by the origin of the cognate epitopes, i.e, the proteins from which they are processed, or, more specifically, nucleoprotein versus glycoprotein. A model in which recruitment time plays a role in the longevity of antiviral T-cell responses during persistent infection is discussed.     

Anesthetic technique influences brain temperature,independently of core temperature,during craniotomy in cats

Because anesthetic technique has the potential to dramatically affect cerebral blood flow and metabolism (two determinants of brain thermoregulation), we tested the hypothesis that, after craniotomy, anesthetic technique would influence brain temperature independent of core temperature. Twenty-one cats (2.7 +/- 0.4 kg; mean +/- SD) undergoing a uniform right parasagittal craniotomy received 1) halothane 1.5% end-expired and normocapnia (HN), 2) halothane 1.5% and hypocapnia (HH), or 3) large-dose pentobarbital and normocapnia (PN) (n = 7 per group). Heating devices initially maintained core and right subdural normothermia (38.0 degrees C). Thereafter, cranial heating was discontinued. Brain-to-core temperature gradients during the 3 h study were greatest in the right subdural area, averaging -2.5 degrees C +/- 0.9 degrees C in HN, -2.5 degrees C +/- 0.8 degrees C in HH, and -4.1 degrees C +/- 1.1 degrees C in PN. Gradients within the unexposed left subdural area and in the right cortex 0.5 and 1.0 cm below the brain surface were -0.8 degrees C +/- 0.5 degrees C to -1.1 degrees C +/- 0.6 degrees C for both HN and HH but were twice this amount in PN (-1.9 degrees C +/- 0.5 degrees C to -2.1 degrees C +/- 0.7 degrees C) (P < 0.05 for PN versus HN and HH). Deep barbiturate anesthesia can reduce brain temperature independently of core temperature, presumably by reducing the metabolic rate and associated brain heat production. The magnitude is sufficient to augment any direct cerebroprotective properties of the barbiturates. IMPLICATIONS: Deep barbiturate anesthesia reduced brain temperature independently of body temperature in cats and significantly more than the reduction seen with halothane anesthesia. The magnitude of temperature reduction was sufficient to account for cerebral protection by barbiturates independently of any other properties of the drug.     

Genetic polymorphisms in the expression and treatment of neuropsychiatric disorders

Recent advances in molecular genetics have greatly increased the understanding of the pathophysiology of certain neurobehavioral disorders and the core symptoms of these disorders. This paper reviews key concepts important in understanding the genetics of neuropsychiatric disorders, and gives an overview of several different types of genetic disorders, including trinucleotide repeat disorders, and functional polymorphisms of monoamine neurotransmitter systems.     

Gross anatomy course content and teaching methodology in allied health: clinicians' experiences and recommendations

The purpose of this study was to sample the experiences and recommendations of clinicians in allied health fields about gross anatomy courses. The objective was to determine if practicing clinicians recommended a course in gross anatomy, and, if so, their recommendations for course content and teaching methodology. Questionnaires were mailed to a random selection of occupational therapists (OTs), physician assistants (PAs), and physical therapists (PTs) licensed in the state of Texas. In addition to demographics, the survey asked 14 questions regarding the experiences and recommendations in seven areas of interest about gross anatomy courses. The responding sample appeared to be representative of the target population. A course in human gross anatomy during professional school was recommended by 96% of OTs, and 100% of PAs and PTs. The single most recommended teaching method was student dissection of human cadavers. Although significant differences were found regarding primary course orientation, a majority favored some form of combined systems and regional oriented courses. A majority of clinicians in each field recommended a gross anatomy course at the beginning of professional training. Specific recommendations were given for content of systems and regional oriented gross anatomy courses. We recommend that the gross anatomy course content and teaching methodologies in allied health areas be responsive to the specific needs of each clinical specialty. Copyright Wiley-Liss, Inc.     

Partial agonist clonidine mediates alpha(2)-AR subtypes specific regulation of cAMP accumulation in adenylyl cyclase II transfected DDT1-MF2 cells

alpha2-Adrenergic receptor (alpha(2)-AR) activation in the pregnant rat myometrium at midterm potentiates beta(2)-AR stimulation of adenylyl cyclase (AC) via Gbetagamma regulation of the type II isoform of adenylyl cyclase. However, at term, alpha(2)-AR activation inhibits beta(2)-AR stimulation of AC. This phenomenon is associated with changes in alpha(2)-AR subtype expression (midterm alpha(2A/D)-AR > alpha(2B)-AR; term alpha(2B) >or =alpha(2A/D)-AR), without any change in ACII mRNA, suggesting that alpha(2A/D)- and alpha(2B)-AR differentially regulate beta(2)-cAMP production. To address this issue, we have stably expressed the same density of alpha(2A/D)- or alpha(2B)-AR with AC II in DDT1-MF2 cells. Clonidine (partial agonist) increased beta(2)-AR-stimulated cAMP production in alpha(2A/D)-AR-ACII transfectants but inhibited it in alpha(2B)-AR-ACII transfectants. In contrast, epinephrine (full agonist) enhanced beta(2)-stimulated ACII in both alpha(2A)- and alpha(2B)-ACII clonal cell lines. 4-Azidoanilido-[alpha-(32)P]GTP-labeling of activated G proteins indicated that, in alpha(2B)-AR transfectants, clonidine activated only Gi(2), whereas epinephrine, the full agonist, effectively coupled to Gi(2) and Gi(3). Thus, partial and full agonists selectively activate G proteins that lead to drug specific effects on effectors. Moreover, these data indicate that Gi(3) activation is required for potentiation of beta(2)-AR stimulation of AC by alpha(2A/D) and alpha(2B)-AR in DDT1-MF2 cells. This may reflect an issue of the amount of Gbetagamma released upon receptor activation and/or betagamma composition of Gi(3) versus Gi(2).