Biomedical subjects
P Georgiou
Publications and source records attributed to P Georgiou.
Degloving injury of the penis from pig bite.
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Upper eyelid island orbicularis oculi myocutaneous flap for periorbital reconstruction.
PURPOSE: To describe the upper eyelid island orbicularis oculi myocutaneous flap, medially or laterally based, for reconstruction of periorbital defects. METHODS: During the past three years we have used the island orbicularis oculi myocutaneous flap in 62 patients with tumors of the periorbital area, with the following indications: (a) anterior lamellar defects of the medial aspect of the upper eyelid, when the peripheral arcade is intact; (b) up to 2/3 anterior lamellar lower eyelid defects; (c) inner and outer canthus defects; and (d) defects of the peripalpebral area (the lateral half of the eyebrow, bridge of the nose and suprazygomatic areas). RESULTS: The flap proved to be flexible, safe, relatively simple, and provided good functional and aesthetic results. Complications were minimal. CONCLUSIONS: The upper eyelid island orbicularis oculi myocutaneous flap may be a useful tool for periorbital reconstruction.
Head and neck soft-tissue reconstruction using the vertical trapezius musculocutaneous flap.
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Upper eyelid orbicularis oculi flap with tarsoconjunctival island for reconstruction of full-thickness lower lid defects.
The reconstruction of full-thickness defects of the lower eyelid after tumor resection is a challenging operation. The great number of techniques for these defects shows that none of them is the operation of choice. The method of reconstruction will be chosen according to the extent of the defect, the missing components of the eyelid structure, the age of the patient, and the quantity and the quality of the surrounding tissues. In this article, we propose, under specific indications, the use of a pedicled myocutaneous orbicularis oculi flap with a tarsoconjunctival island from the upper eyelid to reconstruct full-thickness lower lid defects. The more choices in a surgeon's armamentarium, the more easily the difficult problems of periorbital surgical oncology will be resolved.
Surgical treatment of soft-tissue sarcomas.
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Island mucochrondrocutaneous flap for reconstruction of total loss of the lower eyelid.
The methods usually employed for reconstruction of total lower eyelid loss include (1) tarsoconjunctival flaps from the upper eyelid and skin-graft cover and (2) chondromucosal grafts and local skin-flap cover. We report a technique for coverage of these defects with an island flap involving the full thickness of the ipsilateral nasal wall based on the dorsal (external) nasal vessels, terminal branches of the ophthalmic vessels. The advantages of this method are (1) the main components of the eyelid (skin, tarsus, conjunctiva) are reconstructed in a single short operation, even under local anesthesia, (2) there is one donor area that can be closed primarily without significant deformity, (3) the upper lid remains intact, and ectropion is improbable, and (4) the procedure involves a short hospitalization. As disadvantages we might mention bulkiness of the new eyelid and difficult dissection of the (subcutaneous) pedicle.
Effect of pranlukast, an oral leukotriene receptor antagonist, on leukotriene D4 (LTD4) challenge in normal volunteers.
BACKGROUND: There is increasing evidence to show that leukotrienes are important mediators in asthma. Leukotriene receptor antagonists protect against antigen and exercise challenges in patients with chronic asthma. A study was undertaken to investigate the activity of the leukotriene receptor antagonist pranlukast (SB 205312, ONO-1078) in blocking bronchoconstriction induced by leukotriene D4 (LTD4) inhalation. The selectivity of pranlukast was evaluated using histamine challenge. METHODS: Pranlukast, 450 mg twice daily, was given to eight healthy non-smoking men for five days in a randomised, double blind, placebo controlled, crossover study. The specific airways conductance (sGaw) was measured before and after bronchial provocation with inhaled LTD4 at 3.5 hours after the first dose and at 3.5 and 9.5 hours after the last dose of pranlukast on the morning of day 5. The concentration of LTD4 required to produce a fall in sGaw of 35% (PC35) was calculated. Subjects also underwent a histamine challenge 3.5 hours after a single dose of pranlukast, 450 mg, or placebo. RESULTS: A single dose of pranlukast produced a 10.6 fold increase in PC35sGaw (95% confidence interval (CI) 4.4 to 25.5; p < 0.001) for LTD4 at 3.5 hours after dosing compared with placebo. Three and a half hours after the morning dose of pranlukast on day 5 the PC35sGaw for LTD4 was increased 25.9 fold (95% CI 10.8 to 62.2; p < 0.001) and was still increased sevenfold (95% CI 2.9 to 16.7; p < 0.001) relative to placebo 9.5 hours after administration of the morning dose. No significant differences were noted for the PC35sGaw to histamine for pranlukast compared with placebo. CONCLUSIONS: This study shows that pranlukast is a potent and selective LTD4 receptor antagonist in humans which blocks LTD4 challenge after initial and repeated administration when given twice daily for five days.
Tear and saliva ferning tests in Sjögren's syndrome (SS).
The purpose of this study was to evaluate the tear ferning test (TFT) and the saliva ferning test (SFT) as diagnostic tests for xerophthalmia and xerostomia respectively in patients with SS. Dried samples of freshly produced tears and saliva from: (A) 36 healthy controls without sicca symptoms, (B) 61 patients with primary SS, (C) 53 patients with secondary SS and (D) 22 patients with psychiatric disorders receiving antidepressants, were examined by polarizing light microscopy. All individuals included in the study were postmenopausal women. The crystallization was classified into 4 types according to the ferning phenomenon: uniformity, branching, spreading and integrity (type I normal and II, III, IV abnormal). Abnormal TFT was found in tear samples of: (A) 8/72 normal control eyes, (B) 110/122 prim SS eyes, (C) 86/106 sec SS eyes and (D) 30/44 psychiatric patients' eyes. Abnormal SFT was found in: (A) 6/36 of normal controls, (B) 59/61 of prim SS, (C) 51/53 of sec SS patients and (D) 16/22 of psychiatric patients. The differences of both TFT and SFT of patients with prim SS and sec SS versus controls were significant (p < 0.001). The sensitivity of TFT was found to be high both in prim SS (90%) and in sec SS (81%). In addition the specificities of TFT and SFT were high 89% and 83% respectively. On the other hand the differences of TFT and SFT in psychiatric patients receiving antidepressants versus normal controls were also significant (p < 0.05 and p < 0.025 respectively). According to our data TFT and SFT are simple, sensitive and specific tests to evaluate xerophthalmia and xerostomia in SS and probably in other conditions characterized by mucous membrane dryness.
The single and multiple dose pharmacokinetics of pranlukast in healthy volunteers.
OBJECTIVE: The pharmacokinetics of pranlukast, a leukotriene LTD4 antagonist, were studied in 48 young, healthy subjects after single and repeated oral doses (given every 12 h) ranging from 112.5 to 675 mg. The doses were administered 30 minutes after a light breakfast. RESULTS: Maximal drug concentrations generally occurred between 2 and 6 h after dosing, and there was some evidence of an absorption lag-time. Secondary peaks were observed in the plasma concentration vs. time profiles of many of the study subjects after both single and repeated doses, particularly during the period of maximum drug absorption. In general, after both single and repeated doses, there were related increases in the corresponding Cmax and AUC with a rise in dose, although the increase was diminished at doses above 450 mg. With repeated dosing of pranlukast the mean AUC was generally higher (up to 1.6-fold), and the higher plasma concentrations allowed characterisation of a longer mean t 1/2 than after single dose administration. The mean steady-state trough plasma concentrations attained after evening doses were considerably higher (up to 14-fold) than those obtained after the morning dose. CONCLUSION: The data suggested that the pharmacokinetics of pranlukast are influenced by the time of dosing. Based on analysis of urinary 6 beta-hydroxycortisol excretion, there was no evidence that pranlukast modified the metabolic activity of cytochrome P-450 3A isoenzymes.
A double blind, placebo-controlled study to assess the effect of famciclovir on virus replication in patients with chronic hepatitis B virus infection.
This is the first double-blind controlled study of famciclovir, an oral antiviral agent, as potential therapy for chronic hepatitis B virus (HBV) carries. A fall of more than 90% in HBV DNA levels was noted in six of 11 evaluable patients treated with a 10 day course of oral famciclovir. Further studies with more prolonged therapy are ongoing.
Role of ETS1 in IL-2 gene expression.
The ETS1 gene encodes a sequence-specific transcription factor binding to purine-rich DNA sequences (-GGAA-) present in the transcriptional regulatory regions of many cellular and viral promoters/enhancers, including many lymphokine genes. The ETS1 gene is expressed at high levels in resting T cells and at very low levels after T cell activation, suggesting it may suppress the expression of genes induced during T cell activation. To find out if ETS1 regulates expression of the IL-2 gene, we have ectopically expressed antisense (AS) ETS1 in Jurkat T cells to block the formation of ETS1 proteins. AS ETS1 transfectants produce higher levels of IL-2 compared with sense ETS1 transfectants. Expression of ETS1 DNA binding domain in Jurkat T cells also decreased the production of IL-2. In AS ETS1 transfectants, IL-2 formation was completely inhibited by cyclosporin A and FK590. The IL-2 promoter linked to a chloramphenicol acetyl transferase reporter gene has high activity in AS ETS1 transfectants, indicating that increased IL-2 production seems to be a result of transcriptional induction. Taken together, these results suggest the possibility that ETS1 may act as a negative regulator of IL-2 gene transcription and provide a rational approach toward engineering the endogenous expression of IL-2 in T cells.
Regenerative and non-regenerative calcium transients in hamster eggs triggered by inositol 1,4,5-trisphosphate.
1. Inositol 1,4,5-trisphosphate (InsP3) injected into unfertilized golden hamster eggs elicits a hyperpolarizing response (HR) that is due to stimulation of calcium-activated potassium channels in the egg plasma membrane. 2. A single injection of InsP3 gave a single HR above a threshold value of 0.3 nM. At 5 nM and above, InsP3 induced HRs with no detectable latency. At concentrations between these two values a latency was observed. The amplitude of the HR was independent of InsP3 concentration. 3. A second HR could be elicited by injection of InsP3, but five times more InsP3 was required to trigger a second HR, and 10-100 times more to give an HR of similar magnitude to the first, and there was no latency. 4. The increase in [Ca2+]i in response to an initial injection of 1 nM InsP3 could be resolved into two distinct components: a slow, early rise immediately after InsP3 injection (phase I) followed by a larger and more rapid increase (phase II). The initiation of an HR coincided with the second component of the [Ca2+]i increase. 5. Further injection of InsP3 resulted only in slow, smaller increases in [Ca2+]i that resembled phase I and often did not cause an HR. Phase II appeared to be absent. However, 100-fold greater InsP3 concentrations gave slow, larger Ca2+ transients (and HRs) with no detectable latency. 6. If large amounts of InsP3 were allowed to leak into the eggs constantly from a pipette, repetitive calcium transients were seen. Unlike the sustained repetitive responses seen at fertilization, they were often smaller than the initial transient and less well sustained. However, a subsequent transient could still be elicited on injection of very large concentrations of InsP3. 7. InsP3 can induce regenerative, all-or-none [Ca2+]i increase (CICR) in hamster eggs, often with a long latency, as well as non-regenerative increases. InsP3 injections desensitize CICR and cannot mimic all the features of Ca2+ signalling at fertilization in the hamster egg, in particular, the sensitization of CICR caused by the sperm.
Tear mucus ferning in patients with Sjögren's syndrome.
The purpose of this study is to evaluate the possibility of using the mucus ferning phenomenon of the tears as a diagnostic test for Keratoconjunctivitis sicca in patients with Sjögren's syndrome. Using a polarising light microscope dried samples were tested for ferning phenomenon collected from (1) 36 healthy controls, (2) 21 patients with primary Sjögren's syndrome, and (3) 15 patients with secondary Sjögren's syndrome. Patients with Sjögren's had xerostomia, abnormal salivary gland biopsy and at least two positive tests for Kerato-conjunctivitis sicca. Patterns of mucus crystallization were classified into 5 types according to uniformity, branch spreading and integrity (types I, II normal, types III, IV, V abnormal). Abnormal ferning was found in tear samples of 8 out of 72 normal control eyes, 38 out of 42 with primary Sjögren's syndrome and 25 out of 30 with secondary Sjögren's syndrome. The differences between both primary and secondary Sjögren's syndrome, in comparison to healthy controls, were significant (p < 0.001). The sensitivity of the method was found 90% for primary Sjögren's syndrome and 80% for secondary Sjögren's syndrome. According to our data, tear mucus ferning test is a simple, sensitive and specific test to estimate Keratoconjunctivitis sicca in patients with Sjögren's syndrome.
Epitope mapping of human ETS1 monoclonal antibody.
The epitope for E44 monoclonal antibody (mAb) was mapped using mutated ETS1 proteins lacking different carboxy-terminal regions and by the employment of synthetic oligopeptides spanning the epitope region. This epitope lies around Arg211 of the human ETS1 protein since substitution of Arg211 by Gln211 in the epitope region results in the loss of recognition of the mouse ETS1 protein by E44 mAb. Substitution of Leu214 by valine214 in the epitope region (as is found in the chicken ETS1 and viral Ets proteins) does not alter the capacity of the E44 mAb to recognize this antigen. Taken together, these results suggest that a specific ionic interaction is able to play a pivotal role in the recognition of the ETS1 protein by the E44 mAb.
Linear pharmacokinetics of penciclovir following administration of single oral doses of famciclovir 125, 250, 500 and 750 mg to healthy volunteers.
Twenty healthy male volunteers received single oral doses of famciclovir (125-750 mg), in a randomized, single-blind, crossover study. Plasma and urine concentrations of penciclovir and its 6-deoxy precursor, BRL 42359, were determined and penciclovir plasma concentration-time data submitted to model-independent pharmacokinetic analysis. Peak plasma concentrations of penciclovir were obtained at median times of 0.5-0.75 h after dosing. The areas under the concentration versus time curves (AUC) and the peak penciclovir concentration (Cmax) increased linearly with dose of famciclovir. Time to Cmax, elimination half-life, urinary recovery and renal clearance of penciclovir did not change with increasing dose. Famciclovir was excreted via the kidneys as penciclovir (60%) and BRL 42359 (5%), respectively. Famciclovir was well tolerated by all subjects with a low incidence of adverse effects. In conclusion, penciclovir thus displays linear pharmacokinetics in the anticipated therapeutic dose range of famciclovir.
A delayed all-or-none hyperpolarisation induced by a single Ca action potential in hamster eggs.
A transient change of membrane potential and resistance could be evoked after a long latency (ca. 9 s) by a single calcium action potential in some unfertilized hamster eggs. The estimated reversal potential for the delayed response was close to EK supporting the conclusion that K channels were opened indirectly by the Ca2+ influx through voltage-gated channels. A second action potential elicited after the first did not induce a similar response. A number of treatments (insertion of a Ca2+ pipette, application of Na+-free solution, La3+ or high external pH) likely to raise [Ca2+]i also induced similar large changes of potential and resistance after which a single action potential failed to evoke a large delayed response. The evidence indicates that a small rise in [Ca2+]i activates a slow process leading to a further large increase in [Ca2+]i.
On the mechanism of a pH-induced rise in membrane potassium conductance in hamster eggs.
1. The effect of external pH (pHo) on the membrane potential and resistance of unfertilized zona-free hamster eggs was investigated by intracellular recording techniques. 2. A hyperpolarization of the hamster egg membrane was induced by raising the extracellular pH above 8.0. This hyperpolarization was accompanied by a rise in membrane conductance and was reversible by washing the egg. 3. The estimated value of the reversal potential of the hyperpolarizing response to a solution with pHo 9.5 was about -85 mV. The membrane potential changed linearly with log [K+]o with a slope of 43 +/- 2 mV (mean +/- S.D.; n = 4) for a 10-fold change in [K+]o, while it was unaltered by the removal of Cl- from the solution. 4. The amplitude of the pHo-induced hyperpolarization decreased substantially as [Ca2+]o was lowered from 20 to 1 mM. Sr2+ could substitute for Ca2+ in sustaining the response to high pHo, whereas Ba2+ or Mg2+ could not. 5. Injection of the Ca2+ chelator EGTA into the egg prevented the pHo-induced hyperpolarization suggesting that a rise in [Ca2+]i is required. 6. The rate of rise of Ca2+ action potentials was reversibly enhanced by raising pHo. However, influx through the voltage-gated Ca2+ channels is not involved in initiation and maintenance of the pHo-induced response, as responses were not affected by the Ca2+ channel blocker La3+. 7. The duration of the hyperpolarization evoked by intracellular Ca2+ injection in eggs bathed in normal solution or Na+-free solution was greatly prolonged by raising pHo. 8. It is suggested that a rise in external pH produces an increase in [Ca2+]i, activating a Ca2+-mediated K+ conductance which hyperpolarizes the egg membrane. 9. It is concluded that both a Na+-Ca2+ exchange system and a Ca2+ pump are responsible for Ca2+ extrusion and that inhibition of the Ca2+ pump by high pHo is the chief mechanism underlying the pH-induced hyperpolarization in hamster eggs. Although the Na+-Ca2+ exchange system is facilitated at high pHo, the effect of this facilitation of efflux is outweighed by the inhibition of the Ca2+ pump.