Cellular neurophysiological actions of nociceptin/orphanin FQ.

Cellular actions of nociceptin/orphanin FQ (N/OFQ) resemble those of micro-, delta-, and kappa-opioids, i.e. activation of inwardly rectifying K(+) conductance, inhibition of high-voltage-activated Ca(2+) channel currents, and impediment of neurotransmitter release. Differences in ORL(1) and micro-receptor distribution lead to: 1) more widespread actions of N/OFQ on periaqueductal gray neurons than opioids and 2) differential effects of N/OFQ and opioids in the brainstem. Also, unlike opioids, N/OFQ inhibits T-type Ca(2+) channel current in sensory neurons. Opioids and N/OFQ may modulate glutamate responses in different ways, and certain actions of N/OFQ are potentiated following nerve injury whereas those of micro-opioids are attenuated. Agonists at ORL(1) receptors may therefore be of clinical interest in the management of neuropathic pain.

Transient-evoked otoacoustic emissions in a representative population sample aged 18 to 25 years.

Transient-evoked otoacoustic emissions (TEOAEs) were obtained from 688 ears of a group of 345 young adults aged 18 to 25 years, using the Otodynamics ILO88 in the standard, non-linear mode. Normative data for TEOAEs obtained from 186 otologically normal (ON) ears are presented. In 5 ON ears, there was no recordable response, despite hearing threshold levels better than 20 dB. The main factors affecting the TEOAE level were (1) gender, where females had larger responses on average than males; (2) tympanometric measures, where ears with entirely normal tympanometric measures had larger responses than those with minor tympanometric abnormalities; (3) click stimulus intensity measured in the ear canal, which correlated positively with TEOAE level; and (4) hearing threshold level at 0.5 kHz, which correlated negatively with amplitude. There was also a small effect of social noise exposure in the 2-kHz region of the TEOAE, where the response was lower in those subjects exposed to significant social noise.

The role of the gastroenterology nurse in colorectal cancer screening.

This article provides an overview of the incidence of colorectal cancer in the United States and describes personal and familial factors that increase a person's risk for developing colorectal cancer. Recommendations for each classification of patient risk group are outlined. An in depth review of screening justification for colorectal cancer is presented as well as the American Cancer Society's recommendations for screening. Descriptions of and recommended frequency for fecal occult blood tests, flexible sigmoidoscopy, double contrast barium enema, and colonoscopy are explained as well as the advantages and disadvantages of each test. The role and fundamental responsibilities of the nurse endoscopist are presented based on the author's personal experience. Factors that influence patient compliance are also described, including the role of the gastroenterology nurse in facilitating colorectal cancer screening.

Interventions used by staff nurses to manage "difficult" patients.

Interventions utilized by nurses to manage "difficult" patients and outcomes indicating successful interventions were investigated. Themes included getting the difficult patient label, difficult patient behaviors, reflecting on the label and passing it on, coping with a difficult patient, interventions that worked, and interventions that did not work. Clues indicating that patient behavior was changing were also identified.

Cloning and functional expression of the cDNA encoding a novel ATP-sensitive potassium channel subunit expressed in pancreatic beta-cells, brain, heart and skeletal muscle.

A cDNA clone encoding an inwardly-rectifying potassium channel subunit (Kir6.2) was isolated from an insulinoma cDNA library. The mRNA is strongly expressed in brain, skeletal muscle, cardiac muscle and in insulinoma cells, weakly expressed in lung and kidney and not detectable in spleen, liver or testis. Heterologous expression of Kir6.2 in HEK293 cells was only observed when the cDNA was cotransfected with that of the sulphonylurea receptor (SUR). Whole-cell Kir6.2/SUR currents were K(+)-selective, time-independent and showed weak inward rectification. They were blocked by external barium (5 mM), tolbutamide (Kd = 4.5 microM) or quinine (20 microM) and by 5 mM intracellular ATP. The single-channel conductance was 73 pS. Single-channel activity was voltage-independent and was blocked by 1 mM intracellular ATP or 0.5 mM tolbutamide. We conclude that the Kir6.2/SUR channel complex comprises the ATP-sensitive K-channel.

Spectroscopic and physicochemical studies on the interactions of reversible H+/K(+)-ATPase inhibitors with phospholipid bilayers.

Three complementary techniques, differential scanning calorimetry (DSC), Fourier transform infrared (FT-IR) spectroscopy and nuclear magnetic resonance (NMR) spectroscopy, have been used to characterise the interactions between dimyristoylphosphatidylcholine (DMPC) model biological membranes and two non-covalent inhibitors of the gastric (H+, K+)-ATPase. DSC, FT-IR and deuterium NMR studies of side-chain perdeuterated DMPC (DMPC-d54) support the prediction, based on physical property measurements, that SK&F 96079 partitions readily into phospholipid bilayers, resulting in a slight but measurable disordering of the lipid hydrocarbon side-chain motion and a concomitant reduction in the co-operativity and onset temperature of the gel to liquid crystalline phase transition. However, FT-IR and deuterium NMR studies show that the bilayer structure remains intact even at high (1:4) compound to lipid molar ratios. Proton (1H) NMR nuclear Overhauser effect determinations in sonicated codispersions reveal details of the membrane bound conformations of SK&F 96079. The structurally related analogue SK&F 96464, also studied by 1H-NMR, can be shown, by interpreting the effects of nitroxide-labelled fatty acid relaxation probes, to adopt a well-defined orientation relative to the bilayer, in contrast to SK&F 96079. This orientation directs the proton at the 5-position of the quinoline ring towards the hydrophobic centre of the bilayer, and the quinoline 8-methoxy group towards the surface and hence the aqueous phase. Molecular modelling has been used to rationalise this orientation in terms of hydrogen bonds between the amino NH group of SK&F 96464 and the sn-1 carbonyl group of DMPC, and between the NH group of the protonated quinoline ring of SK&F 96464 and the DMPC phosphodiester group.

Micronucleated erythrocytes as an index of cytogenetic damage in humans: demographic and dietary factors associated with micronucleated erythrocytes in splenectomized subjects.

Erythrocytes containing micronuclei serve as an indicator of genotoxic exposure in splenectomized individuals. Micronucleated erythrocytes, derived from cytogenetically damaged RBC precursors, are not selectively removed from peripheral blood in individuals who lack splenic function. The relationship between micronucleated cell frequencies and demographic, environmental, and dietary factors was examined in 44 subjects with previous splenectomy due to trauma. Their micronucleated cell counts fit a log-normal distribution, with geometric means of 3.3 micronucleus-containing cells/1000 reticulocytes and 2.7/1000 normochromatic erythrocytes. A multiple regression analysis showed that drinking five cups of coffee or tea/day (relative to none) was associated with an approximately 2-fold higher frequency of micronucleated cells. Weaker statistical associations were also noted with micronucleus frequency and the consumption of calcium supplements (associated with a higher frequency) and vitamins A, C, or E (lower frequency). An apparent trend of higher micronucleus counts with age was attenuated when other factors were considered in the regression. Cigarette smoking and decaffeinated coffee consumption were among the factors not associated with elevated micronucleated cell frequencies. Because the occurrence of micronuclei in reticulocytes reflects cytotoxic exposures within the past 3-8 days, it may be possible to test directly the relationship of these factors to micronucleus formation through intervention studies.

Adjunctive use of hyaluronidase in local anaesthesia.

The effects on anaesthesia of adding hyaluronidase to subcutaneous lignocaine were evaluated in a volunteer's forearm. Three beneficial effects were demonstrated: Onset of anaesthetic was immediate. Loss of surface contour was minimal due to rapid spread of infiltrate. The area of anaesthesia was more than doubled compared to the control without hyaluronidase. The indications for the use of hyaluronidase in plastic surgery and its effectiveness as an adjunct to nerve blocks are discussed.

The effects of oral iron supplementation on zinc and magnesium levels during pregnancy.

Serial changes in serum zinc and magnesium concentrations have been studied before conception, throughout pregnancy and at 12 weeks postpartum in 15 normal healthy women not receiving iron supplementation, 10 women receiving iron supplementation but otherwise having healthy pregnancies and five insulin-dependent diabetics who also received oral iron. Relative to pre-pregnancy values zinc concentrations progressively decreased throughout pregnancy reaching a nadir at 36 weeks gestation followed by an increase; pre-pregnancy values were achieved by 12 weeks postpartum. Magnesium concentrations also decreased throughout pregnancy reaching a nadir at 32 weeks gestation increasing thereafter again with pre-pregnancy values achieved by 12 weeks postpartum. Iron supplementation in non-diabetic and diabetic women had no significant effect upon the changes in serum concentration of either zinc or magnesium. These results suggest that the decrease in the concentrations of both elements is a normal physiological adjustment to pregnancy and that iron supplementation does not influence these changes.

Kinetics of N-(phosphonacetyl)-L-aspartate and pyrazofurin depletion of pyrimidine ribonucleotide and deoxyribonucleotide pools and their relationship to nucleic acid synthesis in intact and permeabilized cells.

Pools of uridine triphosphate and cytidine triphosphate are greatly (90%) reduced in cultured L1210 cells exposed to N-(phosphonacetyl)-L-aspartate (PALA) or pyrazofurin; the concentration of the deoxynucleotides deoxycytidine triphosphate, deoxythymidine triphosphate, and deoxyguanosine triphosphate also decreases, but deoxyadenosine triphosphate pools are enlarged. Associated with these pool depletions is a pronounced inhibition of DNA synthesis even when pools are only moderately reduced; RNA synthesis is only slightly inhibited under these same conditions. DNA synthesis in permeabilized preparations of L1210 cells was also more sensitive than was RNA synthesis when the concentrations of ribonucleotide and deoxyribonucleotide triphosphates presented were equivalent to those found in PALA- or pyrazofurin-treated cells. The specific sensitivity to depletion of DNA precursors was also seen in protection of both DNA synthesis and growth of L1210 cells by deoxycytidine and thymidine. This supplement restored deoxycytidine triphosphate, deoxythymidine triphosphate, and deoxyguanosine triphosphate pools to normal but of course did not affect the marked depletions of uridine triphosphate and cytidine triphosphate or the less marked effect of PALA on RNA synthesis. The relative ability of PALA to reduce uridine triphosphate and cytidine triphosphate pool size in L1210 ascites and Lewis lung carcinoma in vivo correlates with the intrinsic sensitivity to this agent.

Progressive atrophy of pancreatic acinar tissue in rats fed a copper-deficient diet supplemented with D-penicillamine or triethylene tetramine: morphological and physiological studies.

This paper describes the progressive effects of severe copper depletion on pancreatic weight, structure, amylase content and responses to secretin and caerulein, as well as a number of general body parameters (appearance, body weight and blood indices). Copper depletion was produced by feeding young rats a copper-deficient diet alone or together with either of the two chelating agents D-penicillamine or triethylene tetramine (Trien). After 6 weeks, the copper-deficient diet alone had relatively little effect on general body parameters but reduced gland weight and the secretory response to caerulein. Addition of D-penicillamine ductal and islet tissue relatively intact; gland weight was markedly reduced, and gland amylase was reduced virtually to zero; and the secretory response to caerulein was almost abolished while that to secretin was reduced. The effects of Trien on general body parameters were less severe; the secretory response to secretin was also less affected, while acinar cell atrophy, gland amylase and the secretory response to caerulein were affected to the same extent as with D-penicillamine. The effects of severe copper depletion on the pancreas were largely irreversible after 13 weeks on a copper-supplemented diet.

From the classroom to the community: teaching primary health workers.

PIP: Students receiving training as medical assistants at the Health Sciences Institute in Maputo, Mozambique, participated in an out of the classroom exercise which provided them with exposure to community attitudes toward illness and medical treatment. Students in the program were drawn from the urban elite, and they were, therefore, socially and educationally quite distinct from the people for whom they would be expected to provide primary health care. 43 students were out in pairs to inteview 1) patients in 2 suburban health centers concerning their beliefs about the causes of disease, and 2) residents in a home for the elderly concerning their beliefs about mental illness and how it should be treated. About half of the respondents gave magical explanations for physical diseases. They tended to give common sense explanations for common and acute disases and magical explanations for chronic illnesses and for mental illnesses. In regard to treatment, most indicated they would first seek modern medical treatment, but if this failed, they would use traditional forsm of treatment. The student's field experiences acted as an impetus for discussing many of the health care issues they will confront in their future work. They became aware of the difficulties involved in collecting and analyzing health data, and they gained an appreciation of the community's beliefs concerning illness. They developed a respect for traditional medicine and recognized the need to work in harmony with the traditional health care system. Also the discussions provided a forum for students to discuss many of the conflicts they themselves were experiencing. Many of the students were brought up in tradition oriented families. These students frequently experienced family and community pressures which were counter to the ideas they were acquiring in class.^ieng