Biomedical subjects
G John
Publications and source records attributed to G John.
Bowel-related abscesses: MR demonstration preliminary results.
The purpose of this study is to describe the appearance of bowel-related abscesses on magnetic resonance (MR) images. Sixteen consecutive patients who had bowel-related abscesses underwent MR examination at 1.5T. MR sequences included T1-weighted fat-suppressed imaging pre- and post-intravenous gadolinium chelate administration (all patients) and breathing-independent single-shot T2-weighted half Fourier turbo (fast) spin echo (6 patients). Patients with pelvic abscesses also underwent sagittal imaging with post-gadolinium T1-weighted images (9 patients) and T2-weighted turbo (fast) spin echo (8 patients). Abscesses were confirmed by open surgery or surgical drainage (6 patients), percutaneous drainage (8 patients), or combined physical examination, fluoroscopic fistulogram, and clinical follow-up (2 patients). Oval-shaped fluid collections were identified in all of the patients, which ranged in diameter from 2 cm to 18 cm, mean: 8 cm. Abscesses were low to intermediate in signal on T1-weighted images, heterogenous and moderately high signal on T2-weighted images, and low signal on post-gadolinium images. A layering effect of lower signal material in the dependent portion of the abscess was noted in abscesses in 6 of 14 patients on T2-weighted images. Post-gadolinium images demonstrated a definable 3- to 7-mm thick abscess wall, which enhanced substantially with contrast. Definition of the wall was best shown on fat-suppressed images post-gadolinium. Substantial enhancement of surrounding periabscess tissues was demonstrated in all cases and was most clearly defined on fat-suppressed images. Image acquisition in two orthogonal planes was of value to demonstrate that fluid collections were oval, and separate from bowel. Image acquisition in the sagittal plane was useful in the evaluation of pelvic abscesses. The results from this preliminary study show that bowel-related abscesses are demonstrable on MR images using gadolinium-enhanced fat-suppressed T1-weighted and turbo (fast) spin-echo T2-weighted sequences. The presence of a thickened, enhancing lesion wall and enhancement of perilesional tissues on T1-weighted fat-suppressed images were observed in all abscesses. A layering effect of low signal intensity material in the dependent portion of the abscess was an important ancillary feature.
Cochlear implantation under local anaesthesia, the Belfast experience.
The profoundly deaf, who gain little or no benefit from conventional hearing aids and meet various criteria are potential candidates for cochlear implantation. The last two decades have witnessed remarkable progress in this field, and it is now a routine clinical procedure. A few adult patients who are potential candidates for cochlear implantation have an unacceptably high risk for hypotensive general anaesthesia due to other systemic conditions. This group has been successfully implanted under local anaesthesia in our centre. The post-implantation progress of these patients was comparable to those carried out under hypotensive general anaesthesia. Data regarding patient selection criteria, examination, anaesthesia, surgery and the outcome are discussed. It was concluded that cochlear implantation under local anaesthesia is a safe and effective procedure for those patients who otherwise may be denied an implant.
F 11440, a potent, selective, high efficacy 5-HT1A receptor agonist with marked anxiolytic and antidepressant potential.
F 11440 (4-methyl-2-[4-(4-(pyrimidin-2-yl)-piperazino)-butyl]-2H, 4H-1,2,4-triazin-3,5-dione) was the outcome of a research effort guided by the hypothesis that the magnitude of the intrinsic activity of agonists at 5-HT1A receptors determines the magnitude of their antidepressant and anxiolytic-like effects. The affinity of F 11440 for 5-HT1A binding sites (pKi, 8.33) was higher than that of buspirone (pKi, 7.50), and somewhat lower than that of flesinoxan (pKi, 8.91). In vivo, F 11440 was 4- to 20-fold more potent than flesinoxan, and 30- to 60-fold more potent than buspirone, in exerting 5-HT1A agonist activity at pre- and postsynaptic receptors in rats (measured by, for example, its ability to decrease hippocampal extracellular serotonin (5-HT) levels and to increase plasma corticosterone levels, respectively). F 11440 did not have detectable antidopaminergic activity (unlike buspirone, which inhibited all of the directly observable behavioral effects of methylphenidate in rats), showed no evidence of antihistaminergic activity (unlike flesinoxan, which protected against the effects of a histamine aerosol in guinea pigs), and had a 70-fold separation between its 5-HT1A agonist and alpha-1 adrenergic antagonist properties (measured as the ability to inhibit the methoxamineinduced increase in blood pressure in rats), unlike flesinoxan, which showed a <3-fold separation. In HeLa cells expressing human 5-HT1A receptors, F 11440 decreased the forskolin-induced increase in AMP, and, based on its maximal effect, was found to have an intrinsic activity of 1.0 relative to that of 5-HT, which was significantly higher than that of buspirone (0.49), ipsapirone (0.46) and flesinoxan (0.93). Consistent with the aforementioned hypothesis, F 11440 produced anxiolytic- and antidepressant-like effects in animal models (i.e., increased punished responding in a pigeon conflict procedure and decreased immobility in a rat forced swimming test, respectively) that were more substantial than those of buspirone, ipsapirone and flesinoxan. Thus, F 11440, shown here to be a potent, selective, high efficacy 5-HT1A receptor agonist, appears to have the potential to exert marked anxiolytic and antidepressant activity in humans.
Increased Pseudomonas aeruginosa adhesion following air drying of etafilcon A soft contact lenses.
PURPOSE: The purpose of this study was to determine the changes in bacterial adhesion resulting from air-drying soft contact lenses. METHODS: An in vitro study was conducted on four sets of identical, unworn etafilcon A soft contact lenses, air-dried for varying periods of time. These lenses were placed in a bacterial suspension, rinsed, ground, and plated in order to determine bacterial adhesion. RESULTS: The increased bacterial adhesion to these high water content, ionic lenses was statistically significant following five minutes of drying. Reversal of the effect was noted after rehydration. CONCLUSIONS: Soft contact lens drying results in increased bacterial adhesion.
Frontal glioma presenting as anxiety and obsessions: a case report.
A 53-year-old gentleman is described, who presented with acute onset of anxiety and obsessional symptoms. The clinical picture was complicated by the presence of mild alcohol withdrawal symptoms and history of excessive drinking for 20 years. A month later, he developed right hemiparesis. CT scan revealed a left frontal tumour, and on histology this was found to be Grade 4 astrocytoma.
In vivo induction of sister chromatid exchanges (SCE) in a tropical fish, Etroplus suratensis (Bloch).
Sister chromatid exchange (SCE) test was applied to a tropical cultured fish, Etroplus suratensis by exposing to known mutagens. Intramuscular injections of methyl methane sulphonate (MMS) and cyclophosphamide (CP) for an exposure period of 96 h resulted in significant increase in the frequency of SCE in gill tissues. MMS induced dose dependent increase in SCE. The findings revealed that the test species in the present study may be used in mutagenicity assays for screening environmental pollutants.
Reconstitution of bacteriorhodopsin and ATP synthase from Micrococcus luteus into liposomes of the purified main tetraether lipid from Thermoplasma acidophilum: proton conductance and light-driven ATP synthesis.
The archaebacterium Thermoplasma acidophilum is cultivated at 59 degrees C in a medium containing sulfuric acid of pH 2. The purified bipolar membrane spanning main phospholipid (MPL) of this organism can be used to produce stable liposomes of 100-500 nm in diameter either using a French pressure cell detergent dialysis or sonication. Despite a potassium diffusion potential of 186 mV very low ionic permeability of sonicated MPL liposomes was measured using the potassium binding fluorescent indicator benzofuran isophthalate PBF1, which measures net K+ uptake. The latter also remained very low, in the presence of the K(+) ionophore valinomycin and palmitic acid. Addition of valinomycin and the potent uncoupler carbonylcyanid-p-trifluormehoxyphenyl-hydrazone (FCCP), led to a stimulation in potassium uptake. The rate of proton flux can be calculated from the net K(+) uptake. Under these conditions MPL liposomes are 1-2 orders of magnitude less permeable than egg yolk lecithin vesicles. The difference in proton permeability becomes even more pronounced with increasing temperature, examined using the fluorescent pH indicator pyranine. Purified bacteriorhodopsin from Halobacterium halobium was reconstituted into MPL liposomes in order to study the light-driven proton uptake in 150 mM KCl following addition of valinomycin, gramicidin, FCCP and Triton X-100. The light-driven proton transport into the liposomes was increased 30-fold by addition of valinomycin decreased by gramicidin and FCCP, and abolished by Triton X-100. Co-reconstituted MPL proteoliposomes containing bacteriorhodopsin and ATP synthase from Micrococcus luteus were capable of light-driven ATP synthesis demonstrating the functional coupling of proton transport and nucleotide generation in liposomal MPL membranes.
Failure of calcium channel blockade to reduce platelet-mediated cyclic flow variations in dogs with coronary stenosis and endothelial injury.
Experimental canine coronary artery stenosis associated with endothelial injury results in a typical pattern of coronary flow characterized by gradual decreases in blood flow to almost zero values followed by abrupt restorations to original levels. Cyclic flow variations (CFVs) are the consequence of recurrent platelet aggregation at the site of the stenosis and subsequent dislodgement of the thrombus. The present study was designed to test the efficacy of diltiazem, nifedipine, and verapamil in inhibiting in vivo platelet aggregation as compared with that of aspirin and ketanserin, two potent reference compounds effective in this model. Except for aspirin, compounds were given as a slow intravenous infusion (i.v.) for 60 min to avoid hemodynamic changes. Diltiazem (0.01 mg/kg/min), nifedipine (3 micrograms/kg/min), and verapamil (0.01 mg/kg/min) were totally inactive against CFVs. A higher dose of verapamil (0.02 mg/kg/min) abolished CFVs in 3 of 4 dogs, but serious side effects were observed [atrioventricular (AV) block and death of 2 animals]. Aspirin (10 mg/kg bolus) caused complete inhibition of CFVs in 4 of 4 dogs, and ketanserin (0.01 mg/kg/min) abolished CFVs in 4 of 5 dogs. These data suggest that calcium channel blockade alone in contrast to cyclooxygenase inhibition or 5-HT2 antagonism cannot inhibit thrombus formation in this model.
Plasma catecholamine levels during functional endoscopic sinus surgery.
Plasma adrenaline and noradrenaline concentrations were measured in 10 consecutive patients during functional endoscopic sinus surgery (FESS). Surgery was preceded by nasal packing with 5 ml 2% cocaine solution, followed by infiltration with 1:80,000 adrenaline and 2% lignocaine. All patients showed a marked rise in plasma adrenaline concentration within 4 min of commencing infiltration, which was not related to the patient's sex, age, weight, the total amount injected, nor the amount injected into the nose. Surgeons should be aware of this marked, but unpredictable, systemic absorption of locally infiltrated vasoconstrictors. Pulse and ECG monitoring should be considered mandatory for such procedures, even when surgery is performed under local anaesthesia.
Breast milk transmission of HIV-1.
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Paracetamol potentiates isaxonine toxicity in vitro.
The toxicity of isaxonine alone and in combination with the known glutathione depletor, paracetamol, was evaluated using rat hepatocyte primary cultures in vitro by measuring morphometric parameters and the leakage of intracellular lactate dehydrogenase into the culture medium. No cytotoxicity was observed with isaxonine at concentrations up to 10(-3) M, whereas paracetamol was cytotoxic at concentrations above 0.6 x 10(-3) M in the culture medium. Paracetamol cytotoxicity (0.6-3.3 x 10(-3) M) was enhanced in the presence of a non-cytotoxic concentration of isaxonine (10(-7) M). Furthermore cytotoxicity was observed when cells were exposed to a combination of non-cytotoxic concentrations of the paracetamol (0.3 x 10(-3) M) and isaxonine (10(-7) M). These findings demonstrate that isaxonine has no direct cytotoxic effect even at high concentrations. However co-administration of isaxonine with paracetamol greatly potentiates cytotoxicity. We suggest that this effect may be related to glutathione depletion within the cell but additional studies are required to verify this hypothesis.
Purification of ATP synthase from beef heart mitochondria (F0F1) and co-reconstitution with monomeric bacteriorhodopsin into liposomes capable of light-driven ATP synthesis.
ATP synthase was isolated from beef heart mitochondria by extraction with N,N-bis-(3-D-gluconamidopropyl)deoxycholamide or by traditional cholate extraction. The enzyme was purified subsequently by ion-exchange and gel-permeation chromatographies in the presence of glycerol and the protease inhibitor diisopropylfluorophosphate. The ATP synthase consisted of 12-14 subunits and contained three tightly bound nucleotides. The co-reconstitution of crude or purified ATP synthase with monomeric bacteriorhodopsin by the method of detergent incubation of liposomes yielded proteoliposomes capable of light-driven ATP synthesis, as detected with a luciferase system for at least 30 min. The reaction was suppressed by the inhibitors oligomycin (> 90%) and dicyclohexylcarbodiimide (85%) and by the uncoupler carbonylcyanide-p-trifluormethoxyphenylhydrazone (> 95%). The purified ATP synthase was apparently free of cytochrome impurities and of adenylate kinase activity, i.e. the enzyme exhibited light-driven ATP synthesis without the dark reaction. For the first time, this is demonstrated with purified ATP synthase from beef heart mitochondria.
Postoperative endophthalmitis resulting from prosthesis contamination in a monocular patient.
Monocular patients who wear an ocular prosthesis may harbor pathogenic conjunctival flora both in the socket and in the contralateral eye. They may therefore be at increased risk of developing endophthalmitis after intraocular procedures. We studied a monocular, prosthesis-wearing, 86-year-old man who underwent cataract extraction, subtotal transpupillary vitrectomy, and intraocular lens insertion. Fulminant endophthalmitis ensued postoperatively, and despite complete vitrectomy and administration of intraocular antibiotics, the eye lost light perception. Intravitreal as well as conjunctival cultures bilaterally grew Proteus mirabilis. The patient disclosed that he cleaned the prosthesis frequently because of discharge. We considered an association between this bacterial colonization and the risk of developing postoperative endophthalmitis and suggest prophylactic measures for treatment of monocular patients undergoing intraocular procedures.
Intraocular tissue plasminogen activator concentrations after subconjunctival delivery.
BACKGROUND: Topical application of recombinant tissue plasminogen activator (tPA) results in detectable intraocular tPA levels. The authors sought to determine whether subconjunctival delivery of recombinant tPA results in enhanced intraocular drug levels. METHODS: One week after first performing a gas vitrectomy in each eye, the authors injected 0.4 ml of a tPA solution (1 or 10 mg/ml) subconjunctivally in one eye of 16 rabbits and 0.4 ml of sterile water in the fellow control eye. Vitreous taps were performed to obtain vitreous samples for measuring tPA concentrations. An anterior chamber paracentesis was then done for each concentration at 15, 30, and 60 minutes. Aqueous and vitreous tPA concentrations were determined using a two-site enzyme-linked immunosorbent assay (ELISA). RESULTS: Vitreous tPA levels were higher than aqueous levels in the treated eyes. Vitreous levels averaged 7 +/- 7 ng/ml for the 1-mg/ml group (n = 7/7) and 202 +/- 230 ng/ml for the 10-mg/ml group (n = 7/8). Aqueous levels were positive in 8 of 16 samples. The authors conclude that subconjunctival delivery of tPA results in both vitreous and aqueous tPA levels.
Procedural safeguards for euthanasia.
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