Proctoscopic polyp delivery after colonoscopic polypectomy.
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Biomedical subjects
Publications and source records attributed to M J Kelly.
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A man presented with frank haematuria and a grossly prolonged prothrombin time. He was later found to have taken an overdose of difenacoum--a 'superwarfarin' rodenticide. The diagnosis was confirmed by a serum concentration of difenacoum of 0.6 micrograms ml-1. Overdosage with superwarfarins is discussed and the need for prolonged treatment with vitamin K1 highlighted.
The effects of estrogen on the response of hypothalamic arcuate neurons to mu-opioid and GABAB agonists were investigated. Intracellular recordings were made from arcuate neurons in slices prepared from ovariectomized guinea pigs that were pretreated with estrogen or vehicle. Estrogen shifted the dose-response curve to the mu-opioid agonist DAMGO (Tyr-D-Ala-Gly-MePhe-Gly-ol) by 3.4-fold; the EC50 for DAMGO was 240 +/- 25 nM in estrogen-treated females versus 70 +/- 12 nM in the controls. The maximal hyperpolarization induced by DAMGO was equivalent in neurons from both groups. The Ke for the naloxone antagonism of the DAMGO response was similar in both groups, which would indicate that the affinity of the mu-receptor was unchanged. To explore where in the receptor/G-protein/K+ channel cascade estrogen may be acting to attenuate the mu-opioid-mediated hyperpolarization, the response to the GABAB agonist baclofen was also tested. Estrogen treatment also shifted the dose-response curve for the baclofen-induced hyperpolarization by 3.3-fold without altering the maximum hyperpolarization; the EC50 shifted from 11.0 +/- 4.0 microM to 36.0 +/- 5.0 microM. All of the neurons were identified after linking the intracellular biocytin with streptavidin-FITC, and a subpopulation of cells in both groups were immunoreactive for beta-endorphin. We conclude that estrogen decreases the functional coupling of the mu-opioid and GABAB receptors to the inwardly rectifying K+ channel possibly through an action on the G-protein.
The strength of active external rotation and of abduction of the shoulder when the humerus was in the plane of the scapula (30 degrees of horizontal flexion anterior to the coronal plane) was measured isokinetically and isometrically in thirty-nine normal volunteers, who were stratified by age and sex. The angles at which peak torque was produced were similar when tested isokinetically and isometrically; these angles were similar for external rotation (at 60 and 30 degrees of internal rotation) and for abduction (at 30 and 60 degrees of abduction). Isometric peak torque was greater than slow-speed (90 degrees per second) isokinetic peak torque, which in turn was greater than fast-speed (210 degrees per second) isokinetic peak torque. There were highly significant differences in strength, measured isokinetically and isometrically, between younger and older men and between older men and older women. The variability of normal values for torque was similar in each group. Repeat testing demonstrated a high reliability of isokinetic measurements and of isometric measurements at angles within the range of the production of peak torque. Complete testing was performed in four normal volunteers before and after a block of the suprascapular nerve. The supraspinatus and infraspinatus components of the rotator cuff contributed a variable proportion to the total strength of abduction (25 to 50 per cent) and external rotation (50 to 75 per cent) throughout the range of motion. This study demonstrated that both isokinetic and isometric testing in the scapular plane are valid methods for measurement of the strength of external rotation and abduction of the shoulder. The data support standardization of the positions for testing the strength of motions of the shoulder: isometric strength of external rotation should be measured in the scapular plane with the shoulder in 45 degrees of abduction and 45 degrees of internal rotation; isometric strength of abduction, in the scapular plane with the shoulder in 45 degrees of abduction; and isokinetic strength of external rotation and abduction, in the scapular plane at 90 degrees per second.
This study assessed factors which may contribute to suboptimal image quality when the modified in vivo erythrocyte labeling technique is used with standard clinical 99mTc activities. For each assessment duplicate or triplicate blood specimens were withdrawn from > or = 10 patients, into syringes containing 700-900 MBq 99mTc as pertechnetate. After incubation the percent of 99mTc which was not bound to erythrocytes at blood re-injection time (%Unbound 99mTc), was measured and compared when one of four factors was varied. The most significant results, in descending order of measured effect were: [table: see text] Our data suggest that the requirements for optimal erythrocyte labeling with standard clinical 99mTc activities are: (A) Erythrocyte tinning time between 10 and 30 min; (B) blood volume > or = 3 ml; (C) blood incubation time > or = 20 min; and (D) Generator ingrowth time < or = 24 hr.
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The results of a physician-directed follow-up of 145 women undergoing the modified Pereyra bladder neck suspension from March 1980 to February 1986 are presented. Median follow-up was 3.5 years (2.0-7.7); 70 percent of patients had follow-up between three and four years postoperatively. All patients had preoperative demonstration of stress incontinence as well as urodynamic evaluation. Fifty-one percent of patients reported no stress incontinence and 76 percent reported that their sense of urinary control was better, or much better at the time of follow-up. Improvement was seen in all grades of stress incontinence. Age, weight, parity, and history of prior anti-incontinence surgery had no significant impact on success rates. Although preoperative urgency symptoms were more common among failure (28% vs 15%), this association was not statistically significant. However, persistent or de novo urgency symptoms postoperatively were highly associated with postoperative incontinence (p less than 0.005). The onset of recurrent incontinence was experienced more than two years postoperatively in 23 percent of the incontinent group.
Quadriceps femoris muscle torque was measured in 40 subjects during transcutaneous neuromuscular electrical stimulation (NMES). Three different electrode types (carbonized rubber, sponge, and adhesive) were used on each subject, permitting determination of the factors that influenced the magnitude of quadriceps femoris muscle torque induced by NMES. This goal was accomplished by entering the various factors into a multiple-regression model. The electrodes differed significantly in their characteristics. The carbonized-rubber electrode delivered the greatest current with the lowest impedance, resulting in the highest knee extension torque. We found that the most important factor in determining torque generation level was the quadriceps femoris muscle's intrinsic ability to be activated (as opposed to electrode size, current, current density, or skin impedance). These data suggest that NMES efficacy is primarily determined by the intrinsic tissue properties of the individual (defined in this study as "efficiency") and is not dramatically changeable by using high stimulation currents or large electrode sizes. The precise physiological basis for interindividual differences in efficiency is not known.
Catecholamine-induced cardiomyopathy associated with pheochromocytoma is a well-recognized but rare entity. Both hypertrophic and dilated variants have been described. We report a case of dilated cardiomyopathy associated with a benign pheochromocytoma that showed complete normalization of left ventricular systolic function following removal of the tumor. Serum noradrenaline and dopamine were significantly elevated without elevation in serum adrenaline levels. This may be the first report in which radionuclide ventriculography was used to document the time course of normalization in LVEF following removal of a pheochromocytoma.
Both gamma-aminobutyric acid (GABA) and the endogenous opioid peptides have pervasive effects on neuroendocrine function. This study examined the effects of selective activation of GABAB and/or mu-opioid receptors on neurons of the arcuate nucelus (ARC) of the rat hypothalamus using intracellular recording of cells in a hypothalamic slice. Some recorded neurons were filled with biocytin allowing subsequent identification and immunocytochemical evaluation for the presence of beta-endorphin. ARC neurons exhibited a broad array of active and passive conductances. Tyr-D-Ala-Gly-MePhe-Gly-ol (DAGOL), a mu-opioid receptor agonist, inhibited spontaneous firing, hyperpolarized 68% of ARC cells in a dose-dependent manner and increased cell conductance. Baclofen, a GABAB receptor agonist, hyperpolarized all cells tested. The reversal potentials for both the DAGOL- and baclofen-induced currents were near that of a potassium conductance. Maximal activation by either of the agonists blocked the effects of the other agonist. Identified beta-endorphin cells were inhibited by both DAGOL and baclofen. The results of these in vitro studies suggest that GABAB and mu-opioid receptors are coupled to the same set of potassium channels and that these channels directly and powerfully inhibit most ARC cells, including beta-endorphin neurons. We propose that convergence of inhibitory influences at the ligand-gated potassium conductance described here may be an important site of interaction for opioidergic, GABAergic and other putative neurotransmitter systems in the control of neuroendocrine circuits by the ARC.
Typical genuine stress urinary incontinence is the result of an anatomic defect, with most procedures designed to restore the support of the proximal urethra and bladder neck. Complications associated with these procedures have been presented to help facilitate an understanding of their etiology and prevention. Careful attention to patient selection, history and physical examination, and surgical detail can prevent most of these complications.
Intracellular recordings were made from 48 hypothalamic arcuate (ARC) neurons under current- and voltage-clamp in slices prepared from female guinea pigs which had been ovariectomized and pretreated with estradiol. Twenty ARC neurons were silent (RMP: -62 +/- 2 mV) and 28 cells were spontaneously active (7.3 +/- 1.1 Hz; threshold -57 +/- 1 mV). The input resistance (Rin), determined in the potential range between -60 and -80 mV, was 358 +/- 30 M omega (n = 38) and ARC neurons showed inward rectification at potentials negative to the equilibrium potential for potassium. The selective mu-opioid agonist Tyr-D-Ala-Gly-MePhe-Gly-ol (DAGO) was applied by pressure pipette application at concentrations of 10 or 20 microM. DAGO decreased spontaneous firing and it hyperpolarized 26 of 31 neurons (9.6 +/- 0.8 mV; range 3-21 mV). Concomitant with the hyperpolarization, DAGO caused a decrease in Rin of 32 +/- 3, and the reversal potential, measured from current-voltage plots, was -94 +/- 2 mV. These effects were mimicked by bath concentrations of 0.5-1.0 microM DAGO. In voltage clamp, DAGO caused an outward current to flow at -60 mV (range 50-185 pA, n = 6). This current reversed at -92 +/- 2 mV (n = 6) and exhibited inward rectification. An additional 6 ARC neurons were tested with DAGO in varying extracellular concentrations of K+ (2.5, 5 and 10 mM) and the reversal potential for the effect of DAGO shifted by 58 mV per decade change in extracellular K+ concentration. DAGO decreased spontaneous postsynaptic potentials in some cells, but TTX (1 microM) had no effect on the ability of DAGO to hyperpolarize the membrane. The hyperpolarization and decrease in Rin induced by DAGO were blocked by the opioid antagonist naloxone (100 nM-1 microM). DAGO responsive cells were unaffected by a kappa-opioid agonist (trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1- pyrrolidinyl)cyclohexyl]benzeneacetamide methanesulphonate; U50,488H), however, 2 of 5 cells also were hyperpolarized by a selective delta-receptor opioid agonist (Tyr-D-Pen-Gly-Phe-D-Pen; DPDPE). The effects of DPDPE, but not DAGO, were blocked by a delta-antagonist (ICI 174,864; 1 microM). The present results indicate that activation of ARC mu-receptors leads to an increase in an inwardly rectifying potassium conductance and a subsequent hyperpolarization of most ARC neurons. We suggest that this mu-receptor-induced hyperpolarization of ARC neurons may underlie the opioid inhibition of reproductive events in the mammal.
We report an analysis of the results obtained in our first 100 studies with indium-111-oxine labelled leukocyte scintigraphy, a diagnostic technique which has recently become available for clinical evaluation within Australia. We used this technique to assess patients with suspected sepsis or inflammation after other commonly used investigations had failed to confirm a diagnosis. Four patient subgroups were evaluated: fever of unknown origin; suspected abdominal or postoperative sepsis; suspected active inflammatory bowel disease; and suspected sepsis or inflammation of bones or joints. The course of all patients was followed for at least three months to establish the accuracy of the technique. The leukocyte labelling procedure took 90 min and imaging was carried out typically 3-6, 24 and occasionally 48 h after reinjection of the labelled autologous leukocytes. In one patient labelling of leukocytes was unsuccessful. In the remaining 99 studies the overall sensitivity of leukocyte scintigraphy was 88% (36 of 41 patients with a proved inflammatory or infective disease focus had positive scan findings); and the specificity was 95% (55 of 58 cases with no proved disease focus had normal scan findings). This series supports the use of this method as the imaging procedure of choice in nuclear medicine for the evaluation of suspected acute sepsis (symptoms less than four weeks' duration), of inflammatory bowel disease and of suspected infections involving appendicular bones which contain no active bone marrow. It is also a useful secondary scintigraphic procedure, after gallium-67-citrate scintigraphy, in patients with suspected infective disorders of more than four weeks' duration.
We have reviewed the experience of our institution and the literature concerning the use of hepatobiliary scintigraphy for the diagnosis of acute cholecystitis. The aim of this study was to assess whether the hepatobiliary scintigraphic finding of initial gallbladder visualization within 30 min is a more reliable criterion for excluding acute cholecystitis than gallbladder visualization within 1 h after tracer injection. In our institution's consecutive series, 113 of 211 hepatobiliary studies had gallbladder visualization within 1 h. Gallbladder visualization time in this group had a log normal distribution, with gallbladder visualization occurring within 30 min in 107 of 113 (95%). Gallbladder visualization occurred between 31 and 60 min in only 6 (5%); nevertheless, our one false negative study came from this small subgroup of patient studies (P = 0.05). Review of the literature (1645 patients with iminodiacetic acid [99mTc-IDA] derivative studies) revealed 6 further timed false negative results with gallbladder visualization within 1 h. Of these studies, in 4 (67%) the gallbladder was visualized between 31 and 60 min and in only 2 before 30 min. One of these latter 2 patients had a rare anatomy. Analysis of the pooled institutional and literature data gave an estimated false negative rate of 21% if the gallbladder was visualized between 31 and 60 min. This was significantly higher (P less than 0.001) than the 0.5% false negative rate when the gallbladder was seen prior to 30 min, but similar to the false negative rate of 16% reported by Weissmann et al. for studies with initial visualization after 1 h.(ABSTRACT TRUNCATED AT 250 WORDS)
In the spring of 1984, British Airways was involved in a major food poisoning outbreak which affected nearly 1000 passengers, aircrew and ground personnel. The operational impact was worldwide and could have resulted in the cessation of the airline's day-to-day operations. The investigation paralleled a major aircraft disaster in the number of national and international agencies involved and in the variety of disciplines engaged. Although the causative organism was rapidly identified (salmonella), and its introduction into the food chain proved to be a key factor, the scale of the outbreak was the result of an interaction of other factors. As with a major aircraft accident, none of the factors alone would have caused the near disaster that occurred.
The genome of Azotobacter vinelandii contains DNA sequences homologous to the structural genes for the Escherichia coli cytochrome bd terminal oxidase complex. Two recombinant clones bearing cydA- and cydB-like sequence were isolated from an A. vinelandii gene library and subcloned into the plasmid vector pACYC184. Physical mapping demonstrated that the cydA- and cydB-like regions in A. vinelandii are contiguous. The cydAB and flanking DNA was mutagenized by the insertion of Tn5-B20. Mutations in the cydB-hybridizing region resulted in the loss of spectral features associated with cytochromes b595 and d. A new locus, cydB, encoding cytochromes b595 and d in A. vinelandii is proposed. A second region adjacent to cydB was also involved in expression of the cytochrome bd complex in A. vinelandii, since mutations in this region resulted in an increase in the levels of both cytochrome b595 and cytochrome d. The regions involved in expression of the cytochrome bd complex and cydB are transcribed in the same direction. Mutants deficient in cytochromes b595 and d were unable to grow on N-deficient medium when incubated in air but could fix nitrogen when the environmental O2 concentration was reduced to 1.5% (vol/vol). It is proposed that the branch of the respiratory chain terminated by the cytochrome bd complex supports the high respiration rates required for the respiratory protection of nitrogenase.
Intracellular recordings were made from hypothalamic arcuate (ARC) neurons with biocytin-filled electrodes under current- and voltage-clamp in slices prepared from ovariectomized guinea pigs which were pretreated with estradiol. Forty-three neurons were identified after linking the intracellular biocytin with streptavidin-FITC and subsequently were examined for beta-endorphin immunoreactivity. Ten of these neurons were immunoreactive for beta-endorphin. beta-Endorphin neurons displayed the following passive membrane properties: RMP:-56 +/- 2 mV; Rin: 439 +/- 66 M omega; tau: 17.5 +/- 2.4 ms; and often fired spontaneously (5.9 +/- 2.2 Hz). These membrane characteristics were not different from identified neurons in the ARC that were not immunoreactive for beta-endorphin. beta-Endorphin neurons exhibited instantaneous inward rectification and time-dependent rectification. The mu-opioid agonist Tyr-D-Ala-Gly-MePhe-Gly-ol (DAGO) decreased spontaneous firing, induced membrane hyperpolarization (12 +/- 2 mV; range 6-22 mV) and decreased the Rin (38 +/- 4%) of the beta-endorphin neurons. These effects of DAGO were blocked by the opioid antagonist naloxone (1 microM) and were not blocked by 1 microM TTX. DAGO-responsive cells were unaffected by either kappa- or delta-receptor opioid agonists. These results indicate that mu-receptors may be autoreceptors on ARC beta-endorphin neurons and that activation of opioid mu-receptors hyperpolarizes beta-endorphin neurons via an increase in K+ conductance. Therefore, opioid peptides may modulate opioid tone through an 'ultra-short loop' feedback control mechanism.
GnRH is synthesized as part of a larger 92-amino acid prohormone (pro-GnRH). In the present study, we examined the effect of gonadectomy and hormone replacement on the processing of pro-GnRH to GnRH in adult male rats. Immunoreactive levels of pro-GnRH and GnRH in acid extracts of preoptic area (POA) and basal hypothalamus (BH) from intact, castrate, and testosterone (T)-treated castrate males were quantified by RIA. In addition, we used immunocytochemistry to detect pro-GnRH-and GnRH-positive neurons and determine the effects of hormone treatment. Three weeks after castration, the pro-GnRH content of the POA was 2-fold greater than the amount found in intact males. Treatment with T for 1 week lowered the prohormone content to intact levels. Although the pro-GnRH content in the BH was about 50% lower than that in the POA, the BH responded to castration and steroid replacement in a manner identical to the POA. The GnRH content of the BH, but not that of the POA, was significantly reduced after castration and increased by T treatment. On the other hand, the total number of pro-GnRH and GnRH cell bodies visualized by immunocytochemistry was not significantly altered by either treatment. These results show that changes in pro-GnRH content vary in inverse relation to changes in GnRH content and suggest that gonadectomy inhibits the enzymatic processing of precursor, while T treatment promotes it.