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Biomedical subjects

F May

Publications and source records attributed to F May.

At least 37 records · Page 2Linked to original sources

Activation of cellular invasion by trefoil peptides and src is mediated by cyclooxygenase- and thromboxane A2 receptor-dependent signaling pathways.

We have investigated the possible functional relationships between cellular invasion pathways induced by trefoil factors (TFFs), src, and the cyclooxygenases COX-1 and COX-2. Pharmacological inhibitors of the Rho small GTPase (C3 exoenzyme), phospholipase C (U-73122), cyclooxygenases (SC-560, NS-398), and the thromboxane A2 receptor (TXA2-R) antagonist SQ-295 completely abolished invasion induced by intestinal trefoil factor, pS2, and src in kidney and colonic epithelial cells MDCKts.src and PCmsrc. In contrast, invasion was induced by the TXA2-R mimetic U-46619, constitutively activated forms of the heterotrimeric G-proteins Galphaq (AGalphaq), Galpha12, Galpha13 (AGalpha12/13), which are signaling elements downstream of TXA2-R. Ectopic overexpression of pS2 cDNA and protein in MDCKts.src-pS2 cells and human colorectal cancer cells HCT8/S11-pS2 initiate distinct invasion signals that are Rho independent and COX and TXA2-R dependent. We detected a marked induction of COX-2 protein and accumulation of the stable PGH2/TXA2 metabolite TXB2 in the conditioned medium from cells transformed by src. This led to activation of the TXA2-R-dependent invasion pathway, which is monitored via a Rho- and Galpha12/Galpha13-independent mechanism using the Galphaq/PKC signaling cascade. These findings identify a new intracrine/paracrine loop that can be monitored by TFFs and src in inflammatory diseases and progression of colorectal cancers.

Cell Line, Transformed↗

[Value of a new non-contact biometer for intraocular crystalline lens power calculation].

PURPOSE: One of cataract surgery's current imperatives involves refraction: the power of the lens implant must be calculated as accurately as possible. Here we present a new method of biometric ocular measurement using the partial optical consistency interferometer. MATERIAL AND METHODS: This investigation studied the axial length measurement of 100 eyes. Five measurements were taken with a classic echobiometric contact technique using the ultrasonic mode; 5 others were taken with the infrared noncontact technique (IOL Master, Zeiss Humphrey). The latter technique is based on interferometric biometry with optical consistency and measurements were taken with an infrared luminous ray. With extreme rapidity and no contact, the device provides a complete biometry, including axial length, keratometry, and anterior chamber depth. It includes a built-in computer. RESULTS: Comparing the ultrasonic and infrared measurements emphasizes the precision and particularly the high reproducibility of the infrared method. The standard deviations of the samples were significantly lower for the 100 measurements. Its limitations depends on the type of cataract since success was not obtained for certain posterior subcapsular opacities. DISCUSSION: This new method of performing a biometry with a partial consistency interferometer contributes a number of advantages: speed, its noninvasive nature with no contact, the high reproducibility of the exam, as well as precise measurements as shown by the difference in the standard deviations of the two methods. CONCLUSION: Biometry using the optical consistency interferometer seems to be a reliable, reproducible, and precise technique that brings great precision for the calculation of the power of the intraocular implant in cataract surgery.

Diagnostic Techniques, Ophthalmological↗

[New medical treatments of glaucoma. New strategies?].

Several new classes of ocular hypotonia medications have recently become available. These include the topical treatments carbonic anhydrase inhibitors, the alpha-2 agonists, the prostaglandin analogues, and a fixed combination of beta-blockers and carbonic anhydrase inhibitors. With an equal or superior efficacy than beta-blockers, these new treatments must be reconsidered as first-line therapy in glaucoma. The long-term safety profile of antiglaucomatous drugs plays an important role in the new trends of medical treatment. These data, better known and detailed over time by clinical experience, are changing our habits and advancing therapeutic strategies for a more effective treatment, better suited to the individual, thus allowing the best quality of life possible.

Adrenergic alpha-Agonists↗

Recurrent aggressive angiomyxoma of the urinary bladder. Case report and review of the literature.

Aggressive angiomyxoma is a rare neoplasm which predominantly involves the female pelvis and perineum. Forty-four cases have been reported in the world literature, including 10 cases in men. To the best of our knowledge, the first case of recurrent aggressive angiomyxoma of the urinary bladder is presented here. Operative management, radiologic features and pathological findings are discussed.

Adult↗

[Trans-scleral diode laser cyclophotocoagulation for the treatment of refractory pediatric glaucoma].

PURPOSE: To evaluate the success rate of contact diode transscleral cyclophotocoagulation (TSCPC) in pediatric refractory glaucoma. PATIENTS: and method: Twenty-eight eyes of 28 patients (age range 5 months to 26 years) with medical and surgical refractory pediatric glaucoma due to primary congenital glaucoma (group 1, 20 eyes) or aphakic congenital glaucoma (group 2: 8 eyes), were included in this retrospective study. All eyes underwent one or more TSCPC with the diode laser (Oculight SLX, Iris Medical) with a minimal follow-up of 2 months. Success was defined as intraocular pressure (IOP) between 6 and 20 mmHg after one or more procedures, with no increase in medical hypotensive therapy, and no progression to another hypotensive procedure. RESULTS: Mean baseline IOP was 29.4 +/- 7.8 mmHg (range 25 to 60 mmHg) and mean follow-up was 10.3 +/- 6.9 months (range 2 to 26 months). Success rates evaluated at 6 and 12 months (Kaplan Meier survival curves) were 54.4% and 27.7% respectively, with one-third of the eyes retreated once or more. These success rates were similar in both groups with a mean baseline IOP decrease of 38.9 +/- 15.9%. Postoperative uncontrolled hypertony occurred in the first 3 months in 6 (21.4%) eyes, leading to surgical IOP management. Other complications were decrease in visual acuity (14.3%), inflammation (25.5%) and phthisis (3.5%). CONCLUSION: TSCPC with the diode laser is a disappointing procedure for the management of refractory pediatric glaucoma, with poor mid-term IOP control and high incidence of complications including severe uncontrolled IOP increase. For these reasons, this cyclodestructive procedure should be considered as a last resort therapy for patients with refractory pediatric glaucoma.

Adolescent↗

Diversity of human endogenous retrovirus class II-like sequences.

Class II human endogenous retroviruses (HERVs), often referred to as mouse mammary tumour virus (MMTV)-like or HERV-K elements, have similarities to several animal infectious retroviruses. Single clones from each of nine class II HERV groups (NMWV 1 to NMWV 9), isolated from a human breast cancer cell genomic library, were sequenced over a 244 bp stretch of the conserved reverse transcriptase region. These sequences were aligned to related exogenous and endogenous retroviruses and a phylogenetic tree was constructed. Sequences with more than 80% identity were considered as members of one group and we report here that the class II HERV family consists of at least ten groups. Three of the sequenced clones, from groups NMWV 3, 7 and 9, could not be related to any other previously identified elements and constituted their own groups. NMWV 8 had no similarity to any retroviral sequences in the sequenced region and is so far considered to be non-retroviral.

Amino Acid Sequence↗

[Diffusion if lidocaine after intracameral injection].

PURPOSE: To determine the lidocaine diffusion space, we compared lidocaine aquous humor concentration in topical anesthesia with 1% lidocaine intracameral injection and in peribulbar anesthesia with 2% lidocaine prior phacoemulsification. MATERIAL AND METHOD: A gas chromatography technique of analyzing 100 microliters aqueous humor was used to detect the presence of lidocaine prior to phakoemulsification cataract surgery in two groups of patients: group A: after peribulbar anesthesia with 10 ml 2% lidocaine, group B: after 1% tetracaine topical anesthesia and 0.5 ml intracameral injection of 1% preservative-free lidocaine. The intracameral volume was estimated mathematically in group B. Endothelial cells loss was analyzed in two groups with non contact specular microscopy. RESULTS: Lidocaine was detected in aqueous humor with a good reliability. The mean concentration after intracameral injection was 6,300 micrograms/ml and was higher than after peribulbar injection. This concentration was near than theorical intracameral rate, suggesting that there was no diffusion in the posterior segment. There was no significant difference in the 2 groups in endothelial cells loss. CONCLUSION: Intracameral injection of lidocaine is an effective technique to anesthetize intracameral structures without diffusion in posterior segment prior to phakoemulsification.

Aged↗

Worldwide telemedicine services based on distributed multimedia electronic patient records by using the second generation Web server hyperwave.

A distributed multimedia electronic patient record (EPR) is a central component of a medicine-telematics application that supports physicians working in rural areas of South America, and offers medical services to scientists in Antarctica. A Hyperwave server is used to maintain the patient record. As opposed to common web servers--and as a second generation web server--Hyperwave provides the capability of holding documents in a distributed web space without the problem of broken links. This enables physicians to browse through a patient's record by using a standard browser even if the patient's record is distributed over several servers. The patient record is basically implemented on the "Good European Health Record" (GEHR) architecture.

Antarctic Regions↗

[Intracameral lidocaine and phacoemulsification under topical anesthesia. Apropos of 80 operations].

PURPOSE: To evaluate the advantage of intracameral unpreserved lidocaine for patient comfort during phacoemulsification under topical anesthesia. METHODS: In this prospective study, we performed 80 phacoemulsifications under topical anesthesia, with tetracaine 1% drops, 10 minutes before and at the start of surgery: 40 patients received 0.3 cc balanced salt solution (BSS) intracameral injection; 40 patients received 0.3 cc unpreserved lidocaine 1% intracameral injection. The same surgical procedure was performed in both groups: 3.2 mm temporal corneal self-sealing incision, capsulorhexis, foldable polyHEMA IOL implantation into the capsular bag. There was no intravenous sedation. RESULTS: Forty-eight percent (19) in the BSS group and 70% (28) in the lidocaine group felt no pain. 10% (4) in the BSS group reported sharp pain during phacoemulsification. During IOL insertion, no pain was reported by 48% (19) in the BSS group, and 75% (30) in the lidocaine group; 10% (4) in the BSS group felt severe pain (significant difference: p < 0.05). Endothelial cell loss was 6% in the BSS group, and 6.4% in the lidocaine group (non significant difference). CONCLUSION: Intracameral lidocaine is safe and effective in decreasing discomfort among patients undergoing phacoemulsification under topical anesthesia.

Administration, Topical↗

[Eye injuries caused by lasers in military and industrial environment. Apropos of 13 cases].

PURPOSE: The aim of this study was to analyse the nature of wavelengths used by military forces, evaluate their clinical consequences in terms of ocular risk, and determine the therapeutic implications and specific preventative measures which should be implemented both in peace- and war-time-settings. MATERIAL AND METHODS: We analyzed retrospectively 13 cases of laser injury (12 patients) treated in our unit over the past 10 years. We recorded the characteristics of the responsible lasers, effects on visual acuity and visual filed, initial ophthalmoscopic and angiographic aspects, treatment undertaken and patient follow-up. RESULTS: Wavelengths were know in only 10 cases. In 9 cases a NdYag laser operating at 1063 nm was involved. The tenth case was an Argon Coirorint laser accident. In three cases the wavelength could not be ascertained because it was confidential information or had been emitted by the enemy and had not been identified. Ocular injury was bilateral in 1 case and unilateral in 12. Retinal lesions were foveolar in 8 cases with an initial visual acuity varying from 1/10 to 10/10. Visual loss depended on the extent of the burn and did not tend to improve despite vasoprotector and corticosteroid treatments. In 2 cases the injury progressed without formation of an epimacular membrane. Retinal lesions were extra-foveolar in 5 cases and in 1 case vitreous hemorrhage required vitrectomy. CONCLUSION: With the widespread use of Yag lasers and the soon to be employed tuneable lasers, there in major risk of serious ocular injury resulting from foveolar burns or peripheral retina trauma with vitreous hemorrhage. In a war situation, a large number of laser casualties producing peripheral vitreous hemorrhage would create an important logistics problem for vitrectomy. The accent must therefore be focused on prevention. Personnel must be informed of the danger and instructed in wearing filter glasses adapted to the wavelengths being used, if known, or a universal photoactivated protective device, as yet a hypothetical possibility.

Accidents, Occupational↗

The effect of hypoxaemia on drug disposition in chronic respiratory failure.

OBJECTIVE: The influence of hypoxaemia on the disposition of two common drugs has been examined in ten adults with stable chronic respiratory failure. METHODS: There were two experimental periods in this cross-over study: during these periods supplemental oxygen was either withheld or administered to impose clinical hypoxaemia or maintain normoxaemia, respectively. Each participant received either oral (40 mg) or intravenous (20 mg) frusemide combined with oral paracetamol (500 mg) on consecutive days of the two experimental periods. RESULTS: The total (bound plus unbound) plasma clearance of frusemide during hypoxaemia (arterial oxygen tension, PaO2 < or = 50 Torr) was not significantly different from the value during normoxaemia (PaO2 > or = 60 Torr) [76.9 and 62.4 ml.min-1]. The volume of distribution was not affected by acute hypoxaemia (121 ml.kg-1 without and 109 ml.kg-1 with oxygen; P > 0.05). Renal and non-renal clearances of frusemide were similar during the period of hypoxaemia (31 and 38 ml.min-1, respectively) compared to respective values during supplemental oxygen delivery (29 and 32 ml.min-1). The absolute bioavailability of frusemide during hypoxaemia (0.62) was not different to that obtained during normoxaemia (0.56). The combined sodium and potassium excretion rate (expressed as a function of the frusemide excretion rate) was not altered by changing the oxygen tension. The pharmacokinetics of paracetamol were unaffected by hypoxaemia.

Acetaminophen↗

High-dose pelvic irradiation followed by ileal neobladder urinary diversion: complications and long-term results.

OBJECTIVE: To determine the risk of post-operative complications in patients receiving high-dose pelvic irradiation before radical cystectomy and urinary diversion. PATIENTS AND METHODS: Of 300 patients who underwent orthotopic bladder replacement at our institution from 1986 to 1994, 11 patients (mean age 63 years, range 53-74) did so after receiving high-dose pelvic irradiation. The indication for cystectomy and urinary reconstruction was bladder cancer in seven men, prostate cancer in two men and a contracted bladder due to combined external pelvic irradiation and afterloading radiotherapy in two women. RESULTS: The post-operative course, including the duration of hospital stay, peri-operative complications and early functional results, did not differ from a control group of non-irradiated patients, and no patients died. The mean follow-up was 22 months (range 10-37) and revealed satisfactory results in seven of 11 patients. A neovesicoperitoneal fistula developed in one woman 10 months after surgery and was repaired by laparotomy. A neovesicovaginal fistula led to supravesical urinary diversion in the second woman. CONCLUSIONS: High-dose pelvic irradiation should not be a primary contra-indication for orthotopic urinary diversion using segments of small intestine. For patients who undergo combined external and afterloading radiotherapy, the indication for orthotopic bladder replacement should be considered critically.

Aged↗

Prostate-specific membrane antigen: a novel folate hydrolase in human prostatic carcinoma cells.

A novel monoclonal antibody has been developed that reacts strongly with human prostatic cancer, especially tumors of high grade. This antibody (7E11C-5) is currently in Phase 3 trials as an imaging agent for metastatic disease. We have cloned the gene that encodes the antigen that is recognized by the 7E11C-5 monoclonal antibody and have designated this unique protein prostate-specific membrane (PSM) antigen. PSM antigen is a putative class II transmembranous glycoprotein exhibiting a molecular size of Mr 94,000. Functionally, class II membrane proteins serve as transport or binding proteins or have hydrolytic activity. Preliminary studies have demonstrated binding of pteroylmonoglutamate (folate) to membrane fractions that also cross-reacted with the PSM monoclonal antibody. We observed substantial carboxypeptidase activity as folate hydrolase associated with PSM antigen. The purpose of our study was to demonstrate that human prostatic carcinoma cells expressing PSM antigen exhibit folate hydrolase activity using methotrexate triglutamate (MTXGlu3) and pteroylpentaglutamate (PteGlu5) as substrates. Isolated membrane fractions from four human prostate cancer cell lines (LNCaP, PC-3, TSU-Prl, and Duke-145) were examined for folate hydrolase activity using capillary electrophoresis. After timed incubations at various pH ranges and in the presence and absence of thiol reagents, separation of pteroyl(glutamate)n derivatives was achieved with an electrolyte of sodium borate and SDS, while absorbance was monitored at 300 nm. The results demonstrate clearly that LNCaP cells, which highly express PSM, hydrolyze gamma-glutamyl linkages of MTXGlu3. The membrane-bound enzyme is an exopeptidase, because it progressively liberates glutamates from MTXGlu3 and PteGlu5 with accumulation of MTX and PteGlu1, respectively. The semipurified enzyme has a broad activity from pH 2.5 to 9.5 and exhibits activity maxima at pH 5 and 8. Enzymatic activity is maintained in the presence of reduced glutathione, homocysteine, and p-hydroxymercuribenzoate (0.05-0.5 mm) but was inhibited weakly by DTT (>/=0.2 mm). By contrast to LNCaP cell membranes, membranes isolated from other human prostate adenocarcinoma cells (PC-3, Duke-145, and TSU-Pr1) did not exhibit comparable hydrolase activity, nor did they react with 7E11-C5 monoclonal antibody. After transfection of PC-3 cells with a full-length 2.65-kb PSM cDNA subcloned into a pREP7 eukaryotic expression vector, non-PSM antigen-expressing PC-3 cells developed immunoreactivity to 7E11-C5 monoclonal antibody and demonstrated folate hydrolase activities and optimum pH activity profiles identical to those of LNCaP cells. The membrane-bound enzymes from both LNCaP- and PC-3-transfected cells also have a capacity to hydrolyze an alpha-linked glutamyl moiety from N-acetyl-alpha-aspartylglutamate. We have identified that PSM antigen is a pteroyl poly-gamma-glutamyl carboxypeptidase (folate hydrolase) and is expressed strongly in human prostate cancer. Cancer cells that express this enzyme are resistant to methotrexate therapy. Those developing future therapeutic strategies in the treatment of prostate cancer that utilize folate antagonists need to consider this mechanism of resistance.

Antigens, Surface↗

NMR-based structural studies of the pNR-2/pS2 single domain trefoil peptide. Similarities to porcine spasmolytic peptide and evidence for a monomeric structure.

NMR spectroscopy measurements have been used to obtain structural information about the pNR-2/pS2 single-domain trefoil peptide. NMR data from 2D (two dimensional) double-quantum-filtered correlation spectroscopy (DQF-COSY), total correlation spectroscopy (TOCSY), NOE spectroscopy (NOESY), rotating frame NOE spectroscopy (ROESY) and 2D 13C-1H heteronuclear single-quantum coherence (HSQC) and 13C-1H HSQC-TOCSY spectra have been analysed to provide essentially complete 1H and 13C sequence-specific assignments for the pNR-2/pS2 protein. From a consideration of the NOE intensities, 3J(NH-alpha CH) coupling constants, 1H and 13C chemical shifts of backbone atoms and amide-proton exchange rates, the pNR-2/pS2 was found to contain two short antiparallel beta-strands (32-35 and 43-46), a short helix (25-30) and a type I beta-turn (11-15). These elements of secondary structure are very similar to those found in the two trefoil domains of pSP for which detailed structural information is already available. Similar 1H chemical shifts were noted for several conserved residues in pNR-2/pS2 and pSP and a characteristic Phe residue with a slowly flipping ring was found in the pNR-2/pS2 variant and in both domains of pSP. The tertiary structures of the domains therefore appear to be very similar in the two proteins and it is likely that the pNR-2/pS2 has the same pattern of disulphide bonds (1-5, 2-4, 3-6) as pSP. Correlation time measurements derived from 1H-1H NOE measurements indicate that the Cys58-->Ser form of the pNR-2/pS2 protein used in this study is monomeric in solution at approximately 2 mM.

Amino Acid Sequence↗