A tribute to Dr Medduma B. Kappagoda

Dr Medduma B. Kappagoda ('Kappa') was a dynamic, unique ophthalmologist. His knowledge and comprehension of ophthalmology were outstanding. He is best remembered for his love of and care for people of all backgrounds, his teaching and his sense of humour.     

Reciprocal interactions between the amygdala and ventrolateral periaqueductal gray in mediating of Q/N(1-17)-induced analgesia in the rat

The opioid peptide, Orphanin FQ/nociceptin (OFQ/N(1-17))(,) its active fragments, and a related precursor peptide each produce analgesia following microinjection into the amygdala of rats. OFQ/N(1-17)-induced analgesia elicited from the amygdala is blocked by amygdala pretreatment of either general, mu, kappa, or delta-opioid antagonists even though OFQ/N(1-17) binds poorly to these receptor subtypes, and the antagonists bind poorly to the ORL-1/KOR-3 receptor. Agonists at mu and kappa opioid receptors as well as beta-endorphin each produce analgesia elicited from the amygdala that is blocked by opioid antagonist pretreatment in the ventrolateral periaqueductal gray (vlPAG) of rats. The present study examined whether pretreatment of general and selective opioid antagonists in the vlPAG blocked OFQ/N(1-17)-induced analgesia on the tail-flick test elicited from the amygdala, and whether pretreatment of general and selective opioid antagonists in the amygdala blocked OFQ/N(1-17)-induced analgesia elicited from the vlPAG of rats. OFQ/N(1-17)-induced analgesia elicited from the amygdala was significantly and markedly reduced following vlPAG pretreatment with a dose range of either naltrexone, beta-funaltrexamine (beta-FNA, mu), nor-binaltorphamine (NBNI, kappa) or naltrindole (NTI, delta). In contrast, opioid antagonists administered into misplaced mesencephalic control placements ventral and lateral to the vlPAG actually enhanced OFQ/N(1-17)-induced analgesia elicited from the amygdala. OFQ/N(1-17)-induced analgesia elicited from the vlPAG was significantly and markedly reduced following amygdala pretreatment with naltrexone and NBNI, to a lesser degree by NTI, and was unaffected by beta-FNA. Yet, opioid antagonists administered into misplaced amygdala control placements were generally ineffective in altering OFQ/N(1-17)-induced analgesia elicited from the vlPAG. Latencies were transiently increased by general, but not selective opioid antagonist treatment alone in the amygdala, but not the vlPAG. These data indicate reciprocal and regional interactions between the amygdala and vlPAG in the mediation of OFQ/N(1-17) by classic opioid receptor subtype antagonists in rats.     

Ultra-long antagonism of kappa opioid agonist-induced diuresis by intracisternal nor-binaltorphimine in monkeys

Kappa opioid receptor (KOR) agonists such as U-50488H and bremazocine are analgesics and diuretics. In monkeys, the selective KOR antagonist, nor-binaltorphimine (nor-BNI), produces a long-lasting antagonism of the antinociceptive effects of U-50488H but not those of bremazocine, suggesting that KOR-mediated antinociception may occur through two distinct KORs. The aim of this study was to characterize the antagonist effect of nor-BNI against the diuretic effects of U-50488H and bremazocine in monkeys. Urine outputs were collected over 3 h subsequent to i.m. administration of KOR agonists. Both U-50488H (0.032-1 mg/kg) and bremazocine (0.00032-0.01 mg/kg) dose-dependently increased urine output and the diuretic effect reached a plateau at higher doses. The maximum effect of either U-50488H or bremazocine was approximately 15 ml/kg/3 h of urine. Pretreatment with intracisternal nor-BNI 0.32 mg significantly blocked both U-50488H (0.18 mg/kg)- and bremazocine (0.0032 mg/kg)-induced diuresis for 20 weeks. However, the same dose of nor-BNI 0.32 mg given subcutaneously was not effective. These results demonstrate that central KOR mediate KOR agonist-induced diuresis in monkeys. More important, this study provides functional evidence for a homogenous population of KOR underlying KOR-mediated diuresis and illustrates a unique pharmacological profile of nor-BNI-induced ultra-long KOR antagonism in vivo.     

Three-choice discrimination in pigeons is based on relative efficacy differences among opioids

RATIONALE: Drug discrimination assays can provide important information on receptor selectivity and relative efficacy to guide the classification and characterization of opioid agonists. OBJECTIVES: A three-choice discrimination was established among high efficacy opioid agonist morphine, low efficacy opioid agonist nalbuphine, and saline to examine the conditions under which differences in relative efficacy might serve as a basis for stimulus control. METHODS: Seven White Carneau pigeons were trained to discriminate among 5.6 mg/kg nalbuphine, 3.2 mg/kg morphine, and saline under fixed ratio 30 (FR30) schedules of food reinforcement. Substitution and antagonism experiments were then conducted with mu, kappa, and delta opioids and naltrexone, respectively and the percent responding appropriate to the training stimuli was determined. RESULTS: Low, intermediate, and high doses of morphine produced > or = 80% saline-, > or = 60% nalbuphine-, and > or = 96% morphine-appropriate responding, respectively. Low and high doses of nalbuphine produced > or = 80% saline- and nalbuphine-appropriate responding, respectively. In substitution tests, low doses of fentanyl and etorphine produced partial nalbuphine-appropriate responding (20-60%) and high doses produced > or = 60-80% morphine-appropriate responding. Intermediate doses of buprenorphine and dezocine produced > or = 60-80% nalbuphine-appropriate responding and high doses produced > or = 80% morphine-appropriate responding. The lower efficacy agonists butorphanol, nalorphine, and levallorphan produced > or = 40-80% nalbuphine-appropriate responding. The kappa agonists spiradoline and U50,488 produced approximately > or = 50% nalbuphine-appropriate responding whereas d-amphetamine, saline, and delta agonists BW373U86 and SNC 80 produced > or = 80% saline-appropriate responding. Naltrexone produced > or = 80% saline-appropriate responding and reversed the stimulus effects of morphine and nalbuphine. CONCLUSIONS: The discrimination between morphine and nalbuphine in pigeons is predominantly based on the relative efficacy differences between morphine, a higher-efficacy mu agonist and nalbuphine, a lower-efficacy mu agonist.     

Pitfalls in the use of kappa when interpreting agreement between multiple raters in reliability studies

ObjectiveTo compare different reliability coefficients (exact agreement, and variations of the kappa (generalised, Cohen's and Prevalence Adjusted and Biased Adjusted (PABAK))) for four physiotherapists conducting visual assessments of scapulae.DesignInter-therapist reliability study.SettingResearch laboratory.Participants30 individuals with no history of neck or shoulder pain were recruited with no obvious significant postural abnormalities.Main outcome measuresRatings of scapular posture were recorded in multiple biomechanical planes under four test conditions (at rest, and while under three isometric conditions) by four physiotherapists.ResultsThe magnitude of discrepancy between the two therapist pairs was 0.04 to 0.76 for Cohen's kappa, and 0.00 to 0.86 for PABAK. In comparison, the generalised kappa provided a score between the two paired kappa coefficients. The difference between mean generalised kappa coefficients and mean Cohen's kappa (0.02) and between mean generalised kappa and PABAK (0.02) were negligible, but the magnitude of difference between the generalised kappa and paired kappa within each plane and condition was substantial; 0.02 to 0.57 for Cohen's kappa and 0.02 to 0.63 for PABAK, respectively.ConclusionsCalculating coefficients for therapist pairs alone may result in inconsistent findings. In contrast, the generalised kappa provided a coefficient close to the mean of the paired kappa coefficients. These findings support an assertion that generalised kappa may lead to a better representation of reliability between three or more raters and that reliability studies only calculating agreement between two raters should be interpreted with caution. However, generalised kappa may mask more extreme cases of agreement (or disagreement) that paired comparisons may reveal.     

MRI Inter-Reader and Intra-Reader Reliabilities for Assessing Injury Morphology and Posterior Ligamentous Complex Integrity of the Spine According to the Thoracolumbar Injury Classification System and Severity Score

ObjectiveTo evaluate spine magnetic resonance imaging (MRI) inter-reader and intra-reader reliabilities using the thoracolumbar injury classification system and severity score (TLICS) and to analyze the effects of reader experience on reliability and the possible reasons for discordant interpretations.ResultsInter-reader agreement between the six readers was moderate (k = 0.538 for the first and 0.537 for the second review) for injury morphology and fair to moderate (k = 0.440 for the first and 0.389 for the second review) for PLC integrity. No significant difference in inter-reader agreement was observed according to the number of years of radiologist experience. Intra-reader agreements showed a wide range (k = 0.538-0.822 for injury morphology and 0.423-0.616 for PLC integrity). Agreement was achieved in 44 for the first and 45 for the second review about injury morphology, as well as in 41 for the first and 38 for the second review of PLC integrity. A positive correlation was detected between injury morphology score and PLC integrity.ConclusionThe reliability of MRI for assessing thoracolumbar spinal injuries according to the TLICS was moderate for injury morphology and fair to moderate for PLC integrity, which may not be influenced by radiologist'' experience.     

Anthropometric survey of the elderly in south-western Nigeria

One hundred and ninety-four subjects aged 65-78 years from rural and urban areas of the south-western region of Nigeria have been surveyed for height, weight, upper arm, hip and waist circumferences. The 24-hour dietary recall technique was also employed to assess their dietary energy intake. In both rural and urban cohorts, male subjects were significantly taller and weighed more (p < 0.05) than female subjects. There were no significant differences in the height of rural groups and their respective urban groups, although urban males and females weighed significantly (p < 0.05) more than their respective rural counterparts. Mean body mass index (BMI) ranged from 18.4 to 21.1kgm^-2, and 73% of all subjects had a BMI below 20% and 10% were below 18.5. Waist, hip and upper arm circumferences of urban cohorts consistently exceeded those of rural subjects, although only for females were these differences statistically (p < 0.05) significant. Significant differences observed in the energy intake (per kg body weight) are offered as one explanation for the superior anthropometric indices of urban as compared with rural elderly in Nigeria.