Conical skin graft in the reconstruction of medial canthal defects.
Explore the source record for details and available documents.
Aged↗
Biomedical subjects
J Harvey
Publications and source records attributed to J Harvey.
Leptin activates ATP-sensitive potassium channels in the rat insulin-secreting cell line, CRI-G1.
1. Whole-cell current-clamp recordings demonstrate that leptin (0.3-10 nm) hyperpolarizes CRI-G1 insulin-secreting cells. This effect is slow on onset and is not reversed on washout of the leptin. 2. Voltage-clamp recordings indicate that leptin activates a potassium conductance in the presence of intracellular ATP (5 mm), but has not effect in its absence. Following activation of ATP-sensitive K+ (KATP) current by diazoxide (0.2 mm), addition of leptin did not alter cell membrane potential or potassium current further. 3. The leptin-induced hyperpolarization and increased potassium conductance are completely inhibited by the application of the sulphonylureas tolbutamide (100 microM) and glibenclamide (0.5 microM). 4. Cell-attached and inside-out single-channel recordings indicate that leptin activates tolbutamide-sensitive KATP channels in CRI-G1 insulin-secreting cells.
Adenosine Triphosphate↗
Public health. Targeting neglect.
40 per cent of health authorities responding accepted all the Health of the Nation targets. More than half of respondents rejected or modified some of the targets. This has implications for a national strategy. Lack of baseline data and difficulties in measuring progress were given as reasons for non-compliance.
Attitude of Health Personnel↗
A postsynaptic interaction between dopamine D1 and NMDA receptors promotes presynaptic inhibition in the rat nucleus accumbens via adenosine release.
The mechanism underlying dopamine D1 receptor-mediated attenuation of glutamatergic synaptic input to nucleus accumbens (NAcc) neurons was investigated in slices of rat forebrain, using whole-cell patch-clamp recording. The depression by dopamine of EPSCs evoked by single-shock cortical stimulation was stimulus-dependent. Synaptic activation of NMDA-type glutamate receptors was critical for this effect, because dopamine-induced EPSC depressions were blocked by the competitive NMDA receptor antagonist D/L-2-amino-5-phosphonopentanoate (AP5). Application of NMDA also depressed the EPSC, and both this effect and the dopamine depressions were blocked by the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), implicating adenosine release in the EPSC depression. A1 receptor agonists also depressed EPSCs by a presynaptic action, causing increased paired-pulse facilitation, but this was insensitive to AP5. Activation of D1 receptors enhanced both postsynaptic inward currents evoked by NMDA application and the isolated NMDA receptor-mediated component of synaptic transmission. The biochemical processes underlying the dopamine-induced EPSC depression did not involve either protein kinase A or the production of cAMP and its metabolites, because this effect was resistant to the protein kinase inhibitors H89 and H7 and the cAMP-specific phosphodiesterase inhibitor rolipram. We conclude that activation of postsynaptic D1 receptors enhances the synaptic activation of NMDA receptors in nucleus accumbens neurons, thereby promoting a transsynaptic feedback inhibition of glutamatergic synaptic transmission via release of adenosine. Unusually for D1 receptors, this phenomenon occurs independently of adenylyl cyclase stimulation. This process may contribute to the locomotor stimulant action of dopaminergic agents in the NAcc.
2-Amino-5-phosphonovalerate↗
Periocular necrotizing fasciitis: a review of five cases.
OBJECTIVE: The purpose of the study is to display a spectrum of clinical presentations of periocular necrotizing fasciitis caused by group A streptococci and to discuss recent trends and treatment of this disease. DESIGN AND INTERVENTION: A case series of five patients (four female and one male) was seen between July 1990 and January 1995 in four university centers. All had clinical evidence of periocular necrotizing fasciitis and grew group A streptococci on wound cultures or had serologic evidence of streptococcal infection. Details of patient presentation, treatment, and outcome are examined. RESULTS: The five patients showed a spectrum of clinical severity from a necrotizing infection confined to the eyelid to a potentially fatal, severe shock-like syndrome characterized by sepsis and multiorgan system failure. A history of trauma often was absent. Patients were treated successfully by a combination of appropriate antibiotics and surgical debridement. CONCLUSIONS: Group A streptococci can cause severe necrotizing infections of the eyelids. Early recognition and prompt treatment can be essential to these patients' survival.
Adult↗
An audit of 267 consecutively excised mammographically detected breast lesions 1989-1993.
Pathology reports and slides were reviewed from 267 mammographically detected impalpable breast lesions, excised after hookwire localisation. There were 182 benign and 85 malignant lesions (benign to malignant ratio of 2.1:1). The invasive cancers tended to be small (mean 13 mm; 50% < or = 10 mm), of low histologic grade (38% Grade I), with a low incidence of lymph node metastases (15%). A high proportion of pure duct carcinoma in situ (DCIS) lesions (21%) was found, and an unusually high proportion of invasive lobular carcinoma (17%). Preoperative fine needle aspiration (FNA) was performed in 95 (36%) cases, including 47 (18%) sampled using sterotactic guidance and 48 (18%) sampled by palpation. The absolute sensitivity of diagnosis of malignancy was 32% and 5% respectively. In 79% of carcinomas further operation was performed, for axillary clearance or re-excision of incompletely excised tumor; this high rate was largely a result of a decision not to use frozen section diagnosis for impalpable lesions and because of the early stages of the development of preoperative needle diagnosis. 58% of invasive cancers, including seven of eight (87.5%) carcinomas with an extensive intraduct component (EIC + ve), and 72% of DCIS were incompletely excised at the first operation. Residual tumor was found in the re-excisions in 26% of EIC - ve invasive carcinomas, 71% of the EIC + ve cases and 56% of DCIS lesions. The malignant lesions had highly favourable prognostic indices. The need for concentration of experience with pre-operative FNA was highlighted. Positive excision margins were a good predictor for residual malignancy, particularly for EIC + ve cases and for DCIS lesions.
Adult↗
Dilated duct pattern at mammography.
PURPOSE: To determine the importance of a dilated duct pattern at mammography. MATERIALS AND METHODS: Mammograms obtained in 46 women with histopathologically proved, asymmetrically dilated ducts were retrospectively studied. The laterality and location of the asymmetrically dilated duct, the presence of branching, and associated findings such as microcalcifications, nipple discharge, and interval change were evaluated. RESULTS: Eleven patients (24%) had malignant results (ductal carcinoma in situ or invasive ductal carcinoma). Among these, six (54%) had suspicious microcalcifications. Nonsubareolar location and interval change are significant (P = .04) variables associated with malignancy. CONCLUSION: Mammographic asymmetrically dilated ducts in a nonsubareolar area that are associated with interval change, suspicious microcalcifications, or both warrant biopsy.
Adult↗
Design of a comic book intervention for gay male youth at risk for HIV.
The prototype of a safer-sex comic book was designed in response to the need for HIV intervention material targetting gay male youth in Toronto. This prototype depicted three separate stories, each based on recorded interviews, and each revolving around the negotiation of condom use between a different pair of characters. The characters were based on observations of respondents. The prototype's plausibility, relevance and attractiveness were assessed through focus groups and an evaluation questionnaire. Results indicated that most readers found the depicted stories pleasing, realistic and personally relevant. Readers found fault with the transitions between the stories and with certain character elements. Suggested solutions and comments about condom use served as directions for further development of the prototype into a finished product.
Adolescent↗
Project has been set up to explore ways of preventing wastage of doctors.
Explore the source record for details and available documents.
Humans↗
Peripheral xenogeneic immunological response to encapsulated bovine adrenal chromaffin cells implanted within the sheep lumbar intrathecal space.
Bovine adrenal chromaffin (BAC) cells were encapsulated in polymer membranes and placed into the lumbar intrathecal (subarachnoid) space of sheep for up to 12 weeks in the absence of immunosuppression. Humoral and cellular immunological responses in the sheep were evaluated over this time course using the following assays: (1) serum-dependent cytotoxic antibody determinations, (2) flow cytometric sheep anti-bovine IgM and sheep antibovine IgG antibody analysis, (3) alterations in cellular immune markers, and (4) T cell responsiveness of the host using one-way mixed lymphocyte reactions. Complement-dependent cytotoxic antibody testing demonstrated that none of the sheep implanted with the encapsulated BAC cells were sensitized to antigens from transplanted cells in the device. There were no alterations of cellular immune markers in the blood of the transplanted sheep and no positive T cell responses were elicited by exposure of unprimed or primed in vivo host lymphocytes to unencapsulated BAC cells in vitro. Morphological analysis of the explanted devices demonstrated that all capsules contained viable cells and 20 of 21 devices released basal and nicotine-stimulated norepinephrine as determined by HPLC analysis. These observations suggest that an encapsulating membrane can provide an immunoisolatory barrier enabling successful xenogeneic transplantation.
Adrenal Medulla↗
Endogenous and exogenous dopamine depress EPSCs in rat nucleus accumbens in vitro via D1 receptors activation.
1. Whole-cell patch clamp recordings were made from nucleus accumbens neurones in slices of rat ventral forebrain. In the presence of picrotoxin (50 microM), the amplitude of 6-cyano-7-nitroquinoxaline-2, 3-dione-sensitive glutamate EPSCs, recorded at holding potentials between -80 and -90 mV, was reversibly reduced by 56 +/- 11% (n = 6) by dopamine (30 microM). The selective dopamine D1 receptor agonists SKF 38393 (10 microM) and SKF 81297A (10 microM), but not the selective D2 receptor agonist quinpirole (10 microM), also reversibly depressed the EPSC by 36-48%. The depression of the EPSC by dopamine was completely blocked by the D1 receptor antagonist SCH 23390 (1 microM), whereas the D2 antagonist (-)-sulpiride (1 microM) was without effect. 2. EPSCs were reversibly depressed by the dopamine mimetic psychostimulants cocaine (1-20 microM) and amphetamine (10-30 microM) by 40 +/- 16 and 62 +/- 9%, respectively, but only in about half of the cells tested (11/23 and 6/13, respectively). Their actions were completely reversed by SCH 23390 (1 microM), indicating that endogenous dopamine can also depress the EPSC via D1 receptors. 3. No discernable effects of dopamine, SKF 81297A, SKF 38393, quinpirole, cocaine or amphetamine were observed on membrane conductance or holding current (at holding potentials of -80 to -90 mV), suggesting that the depression of the EPSC was solely due to an action on presynaptic D1 receptors. 4. In contrast, agents that elevate intracellular levels of adenosine-3':5'-cyclic monophosphate (cAMP) (forskolin (1-10 microM), 3-isobutyl-1-methylxanthine (0.1-1 mM), rolipram (10 microM), and dibutyryl cAMP (0.5-1 mM)) caused a reversible increase in the EPSC amplitude (by 21-150%). Furthermore, in the presence of forskolin (10 microM), the ability of dopamine to depress synaptic transmission was unaffected. 5. Together these data suggest that both exogenous dopamine and dopamine released from intrinsic nerve terminals attenuate glutamate receptor-mediated synaptic transmission in the nucleus accumbens by presynaptic D1 receptor activation. The transduction mechanism underlying this effect does not appear to involve the formation of cAMP.
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
Activation of group I mGluRs potentiates NMDA responses in rat hippocampal slices.
The pharmacology of the metabotropic glutamate receptor (mGluR)-mediated potentiation of N-methyl-D-aspartate (NMDA)-evoked depolarisations in the CA1 region of rat hippocampal slices was investigated using an extracellular grease-gap method. The group I and II mGluR agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD; 10 mu M) potentiated responses to NMDA (15-25 mu M), giving a dose ratio of 0.84 +/- 0.02. The mGluR group I specific agonist (RS3,5-dihydroxyphenylglycine (DHPG) (3-10 mu M) also induced a dose-dependent and reversible enhancement of responses to NMDA (dose ratio for 10 mu M DHPG was 0.77 +/- 0.02). In contrast, the group II selective agonist (2S,1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV; 0.5-1 mu M) and the group III specific agonist (S)-2-amino-4-phosphonobutanoate (L-AP4; 50 mu M) caused little or no potentiation of responses to NMDA. The potentiation induced by 3-5 mu M DHPG was reversibly antagonised by the group I and II antagonist (+)-alpha-methyl-4-carboxyphenylglycine ((+)-MCPG; 1 mM). The present findings demonstrate that activation of group I mGluRs enhance NMDA responses in the hippocampus.
Animals↗
omega-Agatoxin IVA identifies a single calcium channel subtype which contributes to the potassium-induced release of acetylcholine, 5-hydroxytryptamine, dopamine, gamma-aminobutyric acid and glutamate from rat brain slices.
The voltage-dependent calcium channels (VDCCs) involved in K(+)-induced transmitter release have been studied. A maximally effective concentration of the N-type VDCC inhibitor, omega-conotoxin GVIA (GVIA) blocked the release of 5-HT (30%), DA (30%) and ACh (60%) but not that of GABA or glutamate. The O, P and Q-type VDCC inhibitor, omega-agatoxin IVA (Aga IVA, 1 microM), blocked 100% of GABA and glutamate, 70% of DA and about 50% of 5-HT and ACh release. The slopes of the inhibiton curves indicate that it acts on the same, single type of VDCC in all cases. omega-Conotoxin MVIIC (MVIIC) completely inhibited the release of all the transmitters. It is concluded that a single GVIA-insensitive type of VDCC is involved in the K(+)-induced release of all the transmitters and, in addition, N-type VDCCs, with a higher affinity for GVIA than MVIIC, are required for the release of 5-HT, DA and ACh. The non-N-type VDCC is not the O-type as it is not blocked by low (< 10 nM) concentrations of MVIIC. Further resolution of this VDCC into P or Q-type requires more selective antagonists.
Acetylcholine↗
Multilocus enzyme electrophoresis for characterization of Listeria monocytogenes isolates: results of an international comparative study.
Multilocus enzyme electrophoresis (MEE) is a standard technique that is used to elucidate the epidemiology of a variety of bacterial species. Recently, the method has been employed by several laboratories for investigations of clinical and foodborne isolates of Listeria monocytogenes. To assess the sensitivity and reproducibility of MEE in characterising L. monocytogenes isolates for epidemiological purposes and, ultimately, to agree on a standard protocol, seven laboratories participated in a blinded study of 80 strains. The strain collection included both epidemiologically related and unrelated isolates. Each laboratory used its own protocol for MEE. The number of enzymes that were assayed by the laboratories ranged from 8 to 23, and the total number of identified electrophoretic types (ETs) varied between 14 and 25. Of the II pairs of duplicate strains, the number of pairs recognised as identical by the seven laboratories ranged from 3 to 10 (median = 8). From 10 to 18 (median = 15) of the 22 groups of epidemiological related strains were recognised as homogeneous by the different laboratories. The discriminatory power of the method, calculated using Simpson's index of diversity for 69 strains (80 strains minus the 11 duplicates), ranged from 0.827 to 0.925. This relatively low discriminatory power is a consequence of a somewhat low genetic diversity of L. monocytogenes compared to other bacterial species. Efforts should be pursued to standardise the method in order to improve the intra- and inter-laboratory reproducibility.
Alleles↗
Surgical oncology.
Observations about the surgical oncologist and the discipline of surgical oncology are discussed.
Animals↗
Do you clean or contaminate your bronchoscope?
Explore the source record for details and available documents.
Bronchoscopes↗
Stereotactic 14 gauge core-biopsy of the breast: results from 101 patients.
BACKGROUND: Along with fine needle aspiration (FNA) cytology, core-biopsy has become an integral part of the assessment of mammographically detected breast lesions. METHODS: A series of stereotactic large-core-biopsies of mammographically detected breast lesions was studied to assess the accuracy and limitations of the technique in diagnosing malignancy and in giving specific benign diagnoses, and its use in determining surgical management. RESULTS: Eighty per cent of carcinomas were diagnosed as malignant (absolute sensitivity). In 88.8% of the cancers, the core-biopsy was classified as malignant, suspicious or atypical/indeterminate (complete sensitivity), and in 72% of the invasive carcinomas, invasive tumour was present in the core. The technique was more successful for invasive carcinomas than for ductal carcinoma in situ (DCIS) (absolute sensitivity 86.1 and 55.5, respectively; P = 0.28) and for malignant mass lesions than for a mass with associated microcalcifications or for pure microcalcifications (absolute sensitivity 91, 71 and 66.6%, respectively; P = 0.19). In five of the 45 cancers (11.1%), no tumour tissue was present in the core, but all were excised after mammographic review and no delays in diagnosis have been experienced to date. The benign to malignant ratio for excised lesions was 0.11:1. Of the benign lesions, a specific diagnosis was given in 49% (calcifications in the core in a background of fibrocystic change, or postoperative scarring, or fibro-adenoma); the remainder showed non-specific benign findings. All patients where invasive carcinoma was diagnosed in the core underwent axillary clearance and wide local excision or mastectomy at their first operation. CONCLUSIONS: This technique can markedly reduce the number of benign lesions needing open biopsy, and provide information allowing definitive management of most carcinomas at the first operation. The accuracy of core-biopsy was lower in DCIS/microcalcification lesions; extra core samples or a combination of FNA and core-biopsy may be of value in these cases.
Biopsy↗
NMDA receptor dependence of mGlu-mediated depression of synaptic transmission in the CA1 region of the rat hippocampus.
1. The depression of synaptic transmission by the specific metabotropic glutamate receptor (mGlu) agonist (1S, 3R)-1-aminocyclopentane-1,3-dicarboxylate ((1S,3R)-ACPD) was investigated in area CA1 of the hippocampus of 4-10 week old rats, by use of grease-gap and intracellular recording techniques. 2. In the presence of 1 mM Mg2+, (1S,3R)-ACPD was a weak synaptic depressant. In contrast, in the absence of added Mg2+, (1S,3R)-ACPD was much more effective in depressing both the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) and N-methyl-D-aspartate (NMDA) receptor-mediated components of synaptic transmission. At 100 microM, (1S,3R)-ACPD depressed the slope of the field excitatory postsynaptic potential (e.p.s.p.) by 96 +/- 1% (mean +/- s.e.mean; n = 7) compared with 23 +/- 4% in 1 mM Mg(2+)-containing medium (n = 17). 3. The depressant action of 100 microM (1S,3R)-ACPD in Mg(2+)-free medium was reduced from 96 +/- 1 to 46 +/- 6% (n = 7) by the specific NMDA receptor antagonist (R)-2-amino-5-phosphonopentanoate (AP5; 100 microM). 4. Blocking both components of GABA receptor-mediated synaptic transmission with picrotoxin (50 microM) and CGP 55845A (1 microM) in the presence of 1 mM Mg2+ also enhanced the depressant action of (1S,3R)-ACPD (100 microM) from 29 +/- 5 to 67 +/- 6% (n = 6). 5. The actions of (1S,3R)-ACPD, recorded in Mg(2+)-free medium, were antagonized by the mGlu antagonist (+)-alpha-methyl-4-carboxyphenylglycine ((+)-MCPG). Thus, depressions induced by 30 microM (1S,3R)-ACPD were reversed from 48 +/- 4 to 8 +/- 6% (n = 4) by 1 mM (+)-MCPG. 6. In Mg(2+)-free medium, a group I mGlu agonist, (RS)-3, 5-dihydroxyphenylglycine (DHPG; 100 microM) depressed synaptic responses by 74 +/- 2% (n = 18). In contrast, neither the group II agonists ((2S,1'S,2'S)-2-(2'-carboxycyclopropyl)glycine; L-CCG-1; 10 microM; n = 4) and ((2S,1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine; DCG-IV; 100 nM; n = 3) nor the group III agonist ((S)-2-amino-4-phosphonobutanoic acid; L-AP4; 10 microM; n = 4) had any effect. 7. The depolarizing action of (1S,3R)-ACPD, recorded intracellularly, was similar in the presence and absence of Mg(2+)-AP5 did not affect the (1S,3R)-ACPD-induced depolarization in Mg(2+)-free medium. Thus, 50 microM (1S,3R)-ACPD induced depolarizations of 9 +/- 3 mV (n = 5), 10 +/- 2 mV (n = 4) and 8 +/- 2 mV (n = 5) in the three respective conditions. 8. On resetting the membrane potential in the presence of 50 microM (1S,3R)-ACPD to its initial level, the e.p.s.p. amplitude was enhanced by 8 +/- 3% in 1 mM Mg2+ (n = 5) compared with a depression of 37 +/- 11% in the absence of Mg2+ (n = 4). Addition of AP5 prevented the (1S,3R)-ACPD-induced depression of the e.p.s.p. (depression of 4 +/- 5% (n = 5)). 9. It is concluded that activation by group 1 mGlu agonists results in a depression of excitatory synaptic transmission in an NMDA receptor-dependent manner.
Animals↗