Methylene blue soldered microvascular anastomoses in vivo.

OBJECTIVES: solders containing chromophores and proteins enhance the strength of lasered anastomoses. Methylene blue (MB) solder anastomoses in vitro are strong but no in vivo work has been reported. We used an MB solder in vivo and studied the effects of two laser powers on patency and histological appearance. DESIGN, MATERIALS AND METHODS: two groups of 15 rabbits had unilateral end-to-end carotid anastomoses (1.5-2.0 mm) formed using three stay sutures and MB solder. Group 1 anastomoses were formed at 5.7 Wcm(-1) and Group 2 at 2.8 Wcm(-1). The vessels were examined at various points by necropsy for patency and gross macroscopic appearance, with subsequent histological examination. RESULTS: group 2 showed patency of 93.3% v 0% ( p<0.001) endothelialisation of 100% v 26.6% ( p<0.001), giant cell formation 0% v 40.0% ( p<0.01), but stenosis was not significantly different (0% v 13.3% p=0.06). Group 2 showed a higher rate of intimal hyperplasia (IH) (66.6% v 20.0% p<0.05) but neither group exhibited thermal injury or aneurysm formation. CONCLUSIONS: laser soldered microvascular anastomoses were formed in vessels of 1.5-2.0 mm with a high degree of patency. A relationship appears to exist between laser power and anastomotic patency. Methylene blue fading has the potential to act as a switch against over exposure and a visual indicator of solder activation.     

Undergraduate surgical training: variations in program objectives and curriculum implementation across Canada.

BACKGROUND: Although nationally recognized learning objectives for undergraduate surgical education exist, the extent to which Canadian medical schools follow these guidelines has never been established. METHODS: We distributed a survey to all program directors and clinical-teaching-unit coordinators for undergraduate surgery at Canada's 16 medical schools, and subsequently assessed the perceived emphasis placed on learning objectives and student performance, and the impact of instructional tools and teaching locations. RESULTS: Program directors in 15 medical schools responded to the survey. We identified a wide variation in the emphasis placed on basic learning objectives as well as specialty specific learning objectives. The length of rotations, methods of instruction and tools used to grade student performance also varied widely. CONCLUSIONS: Our findings suggest significant variation in the design and implementation of undergraduate surgical education in Canada. This study may serve as a basis for reassessing learning objectives in Canadian undergraduate surgical education.     

'Good prognosis tumours' in breast cancer screening.

The Forrest Report led to the introduction of the breast screening programme with the aim of reducing mortality from breast cancer. In 1989 a breast screening programme was introduced to the South Bucks District and now two cycles have been completed. The findings are of a high yield of good prognosis tumours 71% and 72%, respectively. These encouraging figures are reflected in a high response rate and with a fall in the incidence of non-screen-detected tumours.     

Defining the practice population in fee-for-service practice.

OBJECTIVE: To develop and validate a technique for defining a practice population of discrete individuals based on multiyear family practice fee-for-service billings data. DATA SOURCES/STUDY SETTING: Nineteen family physicians in Ontario, Canada who converted from fee-for-service to capitation payment. Data sources were fee-for-service billings data for the three-year period prior to the conversion from fee-for-service to capitation payment and the rosters of enrolled patients for the first and third years after the change to capitation payment. STUDY DESIGN: The billings-based definition of the physician's practice population was compared against the Year 1 roster. We also compared the billings-based practice population and the Year 1 roster to the physician's Year 3 roster to identify patients who might have been missed during the roster development process. Our principal analyses were an assessment of the sensitivity of the billings-based definition of the practice population (EPP), the positive predictive value of EPP, and the agreement between EPP and the rostered patient population (RPP). We also examined the ratio between EPP and RPP to determine EPP's accuracy in estimating the practice denominator. DATA COLLECTION/EXTRACTION METHODS: The practice population for each physician at the time of conversion from fee-for-service to capitation payment was defined as (a) all persons for whom the physician billed the provincial health insurance plan for at least one visit during the year immediately prior to joining the capitation-funded program; and (b) all additional patients for whom the physician billed the plan for at least one service in each of the two preceding years. Data extraction was carried out within the Ministry of Health in order to preserve the anonymity of patients and physicians. Data were provided to the investigators stripped of patient and physician identifiers. PRINCIPAL FINDINGS: The mean sensitivity and positive predictive value of EPP were 95.3 percent and 87.4 percent, respectively. The level of agreement between EPP and RPP averaged 84.4 percent. The mean ratio of EPP to RPP was 1.21 (95 percent C.I. 1.030-1.213). Correction for roster false-negatives increased the sensitivity, positive predictive value, and agreement between EPP and the practice population, and reduced the mean ratio of EPP to the practice population to 1.068 (95 percent C.I. 1.010-1.127). CONCLUSIONS: The practice population can usefully be defined in fee-for-service family practice on the basis of multiyear fee-for-service billings data. Further research examining alternative encounter-based practice population definitions would be valuable.     

The A-wave of the human electroretinogram and rod receptor function

The amplitude of the leading edge of the a-wave of the human electroretinogram (ERG) was compared with predictions from a computational model of the light-induced responses of rod mammalian receptors. According to this model, a linear process describes the amplitude and time course of the response to relatively low flash intensities and at brief times after the onset of the flash. At higher flash intensities, a nonlinear process, described by the Naka-Rushton function or a saturating exponential, is involved. The primary focus here is on intensity-response data recorded with a clinical ganzfeld apparatus. The leading edge of the rod a-wave recorded from normal observers and patients with congenital stationary night blindness (CSNB) was described by a linear process for flash intensities up to the maximum available flash intensity, 2.0 log scot td-sec. This finding is consistent with the model of the rod's response. It suggests, however, that when ERGs are recorded with clinical systems limited to 2.0 log scot td-sec, these data cannot be used to distinguish between changes in the parameters (eg, semisaturation intensity versus maximum response) of the human rod receptors. Responses to flash intensities up to 3.4 log scot td-sec were recorded using a custom, high-intensity ganzfeld system. Both the linear and nonlinear components of the model were needed to fit the ERGs recorded with this system. This suggests that changes in different receptor parameters can be distinguished with higher intensity flashes.     

The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC): past medical history in children with cancer.

The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC) collected interview and medical information relating to the child's past medical experiences from parents of 555 children diagnosed with cancer and parents of 1110 unaffected matched controls. No significant associations emerged overall for ante-natal care, place and mode of delivery, length of gestation, birth weight, condition at birth, special care, neonatal procedures or breast-feeding. Few risk factors relating to previous illnesses and medication were found, although increasing numbers of illnesses appeared to be associated with an increased risk of childhood cancer, particularly acute lymphoblastic leukaemia. A highly significant excess of case children had not been immunised (p = 0.005). In general, these results indicate that past medical experiences have little influence on the development of cancer in children.     

Parental influences on young girls' fruit and vegetable, micronutrient, and fat intakes.

OBJECTIVE: To evaluate parents' fruit and vegetable intake and their use of pressure to eat in child feeding as predictors of their 5-year-old daughters' fruit and vegetable, micronutrient, and fat intakes. SUBJECTS: Data were obtained from 191 non-Hispanic white families with 5-year-old girls. DESIGN: Parent data included reports of pressure in child feeding and their own fruit and vegetable intake. Girls' intakes of fruits and vegetables, selected micronutrients, and fat were the main outcomes of interest. STATISTICAL ANALYSIS: Structural equation modeling was used to test a model describing relationships among parents' fruit and vegetable intake, parents' use of pressure in child feeding, and daughters' fruit and vegetable, micronutrient, and fat intakes. RESULTS: The model provided a good fit to the data, revealing that girls' fruit and vegetable intake was positively related to their parents' reported fruit and vegetable intake. Parents who consumed fewer fruits and vegetables tended to report greater pressure in child feeding and had daughters who consumed fewer fruits and vegetables. Girls' reported fruit and vegetable intakes were positively related to their micronutrient intakes and negatively associated with fat intake. APPLICATIONS/CONCLUSIONS: This research demonstrates that parents' own fruit and vegetable intake may encourage fruit and vegetable intake in their daughters, leading to higher micronutrient intakes and lower dietary fat intakes. Conversely, pressure to eat may discourage fruit and vegetable intake among young girls.     

The pharmacology of GR203040, a novel, potent and selective non-peptide tachykinin NK1 receptor antagonist.

1. The in vitro and in vivo pharmacology of GR203040 ((2S, 3S)-2-methoxy-5-tetrazol-1-yl-benzyl-(2-phenyl-piperidin-3-y l)-amine), a novel, highly potent and selective non-peptide tachykinin NK1 receptor antagonist, was investigated in the present study. 2. GR203040 potently inhibited [3H]-substance P binding to human NK1 receptors expressed in Chinese hamster ovary (CHO) and U373 MG astrocytoma cells, and NK1 receptors in ferret and gerbil cortex (pKi values of 10.3, 10.5, 10.1 and 10.1 respectively). GR203040 had lower affinity at rat NK1 receptors (pKi = 8.6) and little affinity for human NK2 receptors (pKi < 5.0) in CHO cells and NK3 receptors in guinea-pig cortex (pKi < 6.0). With the exception of the histamine H1 receptor (pIC50 = 7.5). GR203040 had little affinity (pIC50 < 6.0) at all non-NK1 receptors and ion channels examined. Furthermore, GR203040 produced only weak inhibition of Na+ currents in SH-SY5Y neuroblastoma and superior cervical ganglion cells (pIC50 values < 4.0). GR203040 produced only weak antagonism of Ca(2+)-evoked contractions of rat isolated portal vein (pKn = 4.1). The enantiomer of GR203040, GR205608 (2R, 3R)-2-methoxy-5-tetrazol-1-yl-benzyl-(2-phenyl-piperidin-3-y l)-amine), had 10,000 fold lower affinity at the human NK1 receptor expressed in CHO cells (pKi = 6.3). 3. In gerbil ex vivo binding experiments, GR203040 produced a dose-dependent inhibition of the binding of [3H]-substance P to cerebral cortical membranes (ED50 = 15 micrograms kg-1 s.c. and 0.42 mg kg-1 p.o.). At 10 micrograms kg-1 s.c., the inhibition of [3H]-substance P binding was maintained for > 6 h. In the rat, GR203040 was less potent (ED50 = 15.4 mg kg-1 s.c.) probably reflecting, at least in part, its lower affinity at the rat NK1 receptor. 4. In guinea-pig isolated ileum and dog isolated middle cerebral and basilar arteries, GR203040 produced a rightward displacement of the concentration-effect curves to substance P methyl ester (SPOMe) with suppression of the maximum agonist response (apparent pKB values of 11.9, 11.2 and 11.1 respectively). 5. In anaesthetized rabbits, GR203040 antagonized reductions in carotid arterial vascular resistance evoked by SPOMe, injected via the lingual artery (DR10 (i.e. the dose producing a dose-ratio of 10) = 1.1 micrograms kg-1, i.v.). At a dose 20 fold greater than its DR10 value (i.e. 22 micrograms kg-1, i.v.), significant antagonism was evident more than 2 h after GR203040 administration. 6. In anaesthetized rats, GR203040 (3 and 10 mg kg-1, i.v.) produced a dose-dependent inhibition of plasma protein extravasation in dura mater, conjunctiva, eyelid and lip in response to electrical stimulation of the trigeminal ganglion. 7. It is concluded that GR203040 is one of the most potent and selective NK1 receptor antagonists yet described, and as such, has considerable potential as a pharmacological tool to characterize the physiological and pathological roles of substance P and NK1 receptors. GR203040 may also have potential as a novel therapeutic agent for the treatment of conditions such as migraine, emesis and pain.     

A series of novel, highly potent and selective agonists for the kappa-opioid receptor.

1. This paper describes the opioid receptor pharmacology and in vivo activity of several novel benzene-acetamidopiperidine and benzeneacetamidopiperazine analogues. 2. These compounds all showed potent, naloxone-reversible, full agonist activity in the field-stimulated rabbit vas deferens, indicating that they are kappa-opioid agonists; but showed very little activity in the rat or hamster vas deferens, indicating good selectivity with regard to mu- and delta-opioid receptors. 3. They were all potent antinociceptive agents, the most potent compound, GR 103545, having an ED50 value in the mouse abdominal constriction test of 0.25 micrograms kg-1 s.c. The compounds also produced sedation and diuresis, but had little effect on respiration rate or gastrointestinal motility. 4. It is concluded that the seven novel compounds described are all potent and selective agonists for the kappa-opioid receptor.