An in vitro model of ischemic-like stress in retinal pigmented epithelium cells: protective effects of antioxidants.

We have developed a model of in vitro cell oxidative stress in bovine retinal pigment epithelium cells exposed to a ischemia-like condition obtained by interference with glucose utilization through both oxidative phosphorylation and glycolysis. This resulted in a statistically significant decrease of the intracellular ATP levels, which reflects a bioenergetic decline similar to that associated with mitochondrial damage or loss in normal post-mitotic cells aging in vivo. This new model of cellular oxygen stress seems adequate for investigation of the protective action of antioxidants, in agreement with our finding of a statistically significant increase in the ATP levels over the values of the non-treated samples in retinal pigment epithelium cells exposed to the above oxygen stress in medium supplemented with 300 microM vitamin C or 10 mM N-acetylcysteine.

Differential tumor necrosis factor expression by resident retinal cells from experimental uveitis-susceptible and -resistant rat strains.

Experimental autoimmune uveoretinitis (EAU) and endotoxin-induced uveitis (EIU), models for human ocular immunopathological syndromes, result in ocular inflammation in susceptible, but not in resistant rat strains. Moreover rapid photoreceptor degeneration occurs in susceptible rats developing EAU. In order to see whether differences in local ocular immune regulation may account for changes in resistance or susceptibility, we have examined the in vitro production of the cytotoxic cytokine tumor necrosis factor (TNF) by two resident ocular cell types, retinal Müller glia (RMG) and retinal pigmented epithelium (RPE). These cells were isolated and cultured in vitro from Lewis (Lew) (highly susceptible), Lew x Brown-Norway (BN) F1 hybrid (susceptible), BN and Long-Evans (LE) (resistant or poorly susceptible) rats. Constitutive production of the cytokine TNF, or its liberation in response to either interferon-gamma (IFN-gamma) or lipopolysaccharide (LPS) alone, was very low in RMG and RPE cells, irrespective of the strain. It was strongly induced by combined treatment with IFN-gamma and LPS in Lew RMG and RPE cells (mean values of 140 and 150 pg/10(5) cells, respectively) and in Lew x BN F1 RMG and RPE cells (mean values of 125 and 190 pg/10(5) cells, respectively), much less so from BN RMG and RPE cells (30 and 20 pg/10(5) cells, respectively) and remained undetectable in LE RMG and RPE cells. Hence susceptibility to EAU and EIU in vivo is correlated with the extent of TNF production by these two cell types under in vitro conditions, which may play a key role in initiating or perpetuating local immune responses.

Modulation of cytokeratin subtype, EGF receptor, and androgen receptor expression during progression of prostate cancer.

After initial regression in response to androgen deprivation, most prostate cancers develop resistance to endocrine therapy. Identification of cellular and molecular changes occurring during endocrine therapy-induced regression and subsequent hormone insensitivity may point to mechanisms underlying the transition to hormone-independent prostate cancer. A series of untreated (n = 24), regressed (n = 15), and endocrine therapy-resistant (n = 10) prostatic adenocarcinomas were analyzed using immunohistochemistry with regard to cytokeratin 5 and 18, androgen receptor (AR), and epidermal growth factor receptor (EGF-R) expression in tumor cells. Using semiquantitative reverse transcription-polymerase chain reaction, the amount of AR mRNA also was determined. In regressed and therapy-resistant prostate cancers, an increase in cytokeratin 5-positive tumor cells was noted when compared with untreated carcinomas. Similarly, the proportion of EGF-R-positive tumor cells increased in the treated cases, whereas the proportion of AR-positive tumor cells dropped in regressed carcinomas and increased in hormone-refractory cancers. In the latter group, an eightfold higher level of AR mRNA was observed when compared with the other cases. Changes in the proportion of cytokeratin 5 and EGF-R-positive tumor cells suggests that during androgen deprivation an enlarged subpopulation of tumor cells with combined features of basal and secretory phenotypes arises. The increased proportion of AR-positive tumor cells during the transition from the regression phase to the hormone escape phase points to an important role of AR overexpression in this process.

Acute and transient ST segment elevation during bacterial shock in seven patients without apparent heart disease.

Acute elevation of the ST segment in several ECG leads was observed in seven patients with bacterial shock during the course of therapy. Six patients had bacterial pneumonia, one had acute cholecystitis, and none had a previous history of heart disease. At the onset of the ST elevation, all patients were receiving dopamine infusion, which in four of them was inadvertently increased shortly before the ECG changes, the ST elevation was not associated with chest pain, pericardial friction rub, or acute changes in the heart rate, or arterial blood pressure. In four patients the maximum ST elevation was greater than or equal to 5 mm. In each instance the ST segment returned to the isoelectric line within 24 hours, and subsequent development of Q waves or changes in the QRS was not observed. Although the existence of an acute pericarditis or an acute myocarditis as possible causes of the ST elevation cannot be fully ruled out, the sudden onset, prominent magnitude, and brief duration of the ST elevation are perhaps more indicative of an acute ischemic event, possibly related to a transient coronary vasoconstriction induced by the dopamine infusion.

Laparoscopic radical prostatectomy: preliminary results.

OBJECTIVES: To evaluate our preliminary experience with laparoscopic radical prostatectomy. The indications for laparoscopy are currently being extended to complex oncologic procedures. METHODS: Forty-three men underwent laparoscopic radical prostatectomy. We used five trocars. The surgical technique replicates the steps of traditional retropubic prostatectomy, except that the rectoprostatic cleavage plane is developed transperitoneally at the beginning of the procedure. In the first 10 patients, we performed the vesicourethral reconstruction with interrupted sutures; in the remaining 33 patients, we performed it with two hemicircumferential running sutures. The specimen was removed through the umbilical port site. RESULTS: Once the developmental phase with the first 10 patients was concluded, the median operating time was 4.3 hours without pelvic lymphadenectomy, and the median postoperative bladder catheterization was 4 days. Two (4.7%) of 43 patients underwent transfusion. Twelve patients (27.9%) had positive surgical margins; all patients had a postoperative prostate-specific antigen level of less than 0.1 ng/mL at 1 month. Rectal injury occurred in 1 patient, requiring colostomy, and 4 patients had urethrovesical anastomotic leakages requiring surgical repair. One month postoperatively, 36 patients (84%) were fully continent (no leakage). Six patients had had erections, and four stated they had had sexual intercourse. CONCLUSIONS: Laparoscopic radical prostatectomy has evolved to a fully standardized and reproducible procedure. The short-term oncologic and functional efficacy rates are equivalent to those for open surgery. The operating time is reasonable once the learning curve is over, and postoperative morbidity is diminished. Because of the improved visual accuracy, permitting more precise dissection, this technique has the potential to become an important advancement in urologic surgery.

Laser in situ keratomileusis to correct high myopia.

PURPOSE: To evaluate the effectiveness, predictability, and safety of laser in situ keratomileusis (LASIK) in 143 eyes with myopia from 8.00 to 20.00 diopters (D). SETTING: Alicante Institute of Ophthalmology, University of Alicante School of Medicine, Alicante, Spain. METHODS: This prospective study comprised 143 eyes (94 patients) that had LASIK with the Chiron Automated Corneal Shaper and the VISX 20/20 excimer laser using a multizone profile and a sutureless hinged corneal flap technique. RESULTS: Uncorrected visual acuity of 20/40 or better in 45.0% of eyes 3 months postoperatively and in 46.4% at 6 months. Best corrected visual acuity (BCVA) improved by 0.07 at 3 and 6 months and was stable after 3 months. Mean spherical equivalent was -13.19 diopters (D) +/- 2.89 (SD) preoperatively and +0.51 +/- 1.63 D at 3 months and +0.18 +/- 1.66 D at 6 months postoperatively. At 3 months, spherical equivalent was within 1.00 D of emmetropia in 57.5% of all eyes, 71.0% of eyes with a baseline refraction from -8.00 to -11.99 D (n = 59), 44.4% with a baseline refraction from -12.00 to -15.99 D (n = 54), and 53.0% of eyes with a baseline refraction from -16.00 to -20.00 D (n = 30). The respective 6 month percentages were 60.0, 72.4, 46.0, and 50.0%. The regression of effect was similar in all groups (approximately 0.50 D) between 1 and 3 months, although the high myopia group had further regression. Significant corneal steepening and an increase in corneal thickness occurred between 1 and 3 months. Flap thickness was always less than predicted with both the 130 microns plates, and achieved laser ablation was deeper than programmed. The relationships between postoperative refraction and preoperative keratometry and postoperative refraction and the difference in achieved versus programmed ablation were significant. Complications at 6 months included epithelial ingrowth, corneal flap melting, decentered ablation, and irregular astigmatism with loss of BCVA, although none was vision threatening. CONCLUSION: In this study, LASIK was effective and predictable in the correction of high myopia but was more accurate for myopia up to 12.00 D. Current surgical algorithms must be modified to improve predictability in higher corrections. Longer follow-up is necessary to evaluate long-term incidence of vision-threatening complications.

Protective properties of viscoelastic substances (sodium hyaluronate and 2% hydroxymethylcellulose) against experimental free radical damage to the corneal endothelium.

Hydrogen peroxide (H2O2) has potent oxidant properties due to the action of free radicals (OH.) induced from its degradation. The free radicals specie derived from H2O2 are extremely toxic to the corneal endothelium and quickly induce corneal edema. In the present work, in order to ascertain the endothelial cell protection from viscoelastic substances, we have studied experimental corneal endothelial cell damage caused in the rabbit eye after intracameral injection of different H2O2 concentrations, with and without previous filling and washing out of two widely used viscoelastic substances from the anterior chamber such as 1% sodium hyaluronate (Healon) and hydroxypropylmethylcellulose (HPMC). We observed a dose-dependent endothelial damage in the controls. The experimental groups protected with Healon or HPMC showed statistically fewer corneal endothelial cell lesions than the control group (p < 0.001) for all of the concentrations used. Healon showed superior protective properties than HPMC at higher H2O2 concentrations (100 mM). However, HPMC was superior with 1 and 10 mM peroxide. From this experimental evidence, we conclude that Healon and HPMC are effective as protectors against the corneal endothelial lesions caused by free radicals. This finding may explain some of the beneficial effects of these viscoelastic substances.

The antiinflammatory effect of nordihydroguaiaretic acid in endotoxin induced uveitis in rabbits.

The authors evaluated the anti-inflammatory effect of nordihydroguaiaretic acid (NDGA) and dexamethasone on an endotoxin induced uveitis (EIU) model, in rabbits. Six groups of 12 rabbits were formed. In groups II to V a uveitis was induced by an intravitreal injection of 5 ul of saline, containing 10 ng of endotoxin of Salmonella typhi. In group I, which is considered as the control, an intravitreal injection of 5 ul of saline was given. Each group received a different treatment and the inflammatory reaction was evaluated after 24 hours, quantifying the following parameters: clinical scoring, cells, proteins, PGE2, LTB4 in the aqueous and histopathological scoring. Compared to group II (non treated), group VI (treated with intraperitoneal 2 mg/kg dexamethasone) showed a decrease of 61% of proteins and LTB4, and a decrease of more than 90% of the other parameters studied. All these differences are statistically significant (p < 0.001). In groups III (intraperitoneal NDGA 10 mg/kg), IV and V (NDGA 1% topically every two and four hours respectively), the proteins showed a change of less than 5.5% and the PGE2 was reduced to around 50% compared to group II; these changes are not statistically significant (p > 0.05). The authors observed an important and significant decrease of the other parameters when compared to group II (p < 0.001). It can be concluded that at the doses given here, NDGA shows an effective action on the lipoxygenase pathway without an increase of the production of PGE2.

Inhibition of COX in ocular tissues: an in vitro model to identify selective COX-2 inhibitors.

The aim of this work was to study the regulation of LPS-stimulated PGE 2 synthesis by traditional NSAIDs (piroxicam and diclofenac) and a selective COX-2 inhibitor (NS-398), in cultured bovine corneal endothelial cells and retinal pigmentary epithelial cells. The IC50 values of piroxicam and diclofenac were compared with IC50 values of NS-398, diclofenac, in both types of cells, showed higher potency than piroxicam. Diclofenac seemed to be a COX-2 inhibitor because its IC50 values were similar to the IC50 values of NS-398. We suggest that this in vitro cell assay system could be useful for identifying compounds that selectively inhibit COX-2 in ocular tissues.

[The long-term efficacy of fibrinolytic treatment in the acute phase of a myocardial infarct. A comparison with a control group]. / Eficacia a largo plazo del tratamiento fibrinolítico en la fase aguda del infarto de miocardio. Comparación con un grupo control.

BACKGROUND: The follow-up of patients with an acute myocardial infarction treated with fibrinolysis and that of patients treated with conventional therapy was analyzed. PATIENTS AND METHODS: The study cohort included: 1) 214 patients with a first acute infarction of < or = 4 hours and with < or = 70 years of age who participated in a randomized study comparing the effects of streptokinase (SK, n: 110) vs conventional treatment (control, n: 104), and 2) a total of 361 patients with a myocardial infarction of < or = 6 hours and < or = 75 years old treated with fibrinolytic agents. RESULTS: In-hospital mortality in the randomized study was 11% for the control group and 7% for the SK group, and 8.8% for the rest of patients treated with fibrinolysis. Mortality during follow-up in the randomized study (7.0 +/- 1.5 years) was 10.7% for the SK group and 19.3% for the control group. Ejection fraction was significantly lower in non survivors than in survivors (36.7% vs 50.8%, (p < 0.0001) and among patients with an ejection fraction < 50%, follow-up mortality was significantly lower in those with a complete recanalization (TIMI 3) than in those with an absent or incomplete recanalization (TIMI 0-2) (98% vs 22%). Follow-up mortality for the rest of patients treated with fibrinolysis (2.6 +/- 1.6 years) was 9%. CONCLUSIONS: 1) The reduction of in-hospital mortality by fibrinolysis appears to increase in the long-term follow-up, and 2) the long-term survival seems to be related not only to the left ventricular function but also to the extent of angiographic recanalization.

[Dementia syndrome and intercurrent pathologies in the elderly. A study of 100 patients over 75 years of age in a geriatrics internal medicine unit]. / Syndrome démentiel et pathologies intercurrentes chez les sujets âgés. Etude de 100 patients de plus de 75 ans en Unité de médecine interne gériatrique.

Elderly people with dementia are admitted in ever increasing number to Internal Medicine units for exploration of dementia and treatment of intercurrent diseases. The purpose of this prospective study of 100 demential subjects aged 75 or more (mean: 85.3 +/- 5.4 years) was to discover the cause of dementia, to investigate the associated diseases and to evaluate the effects of treatment of these pathologies on the patients' cognitive performance. The mean duration of stay in hospital was 25.5 +/- 14.5 days (extreme: 6-100 days); 69 returned home, 17 were institutionalized and 14 died. Dementia was degenerative and of the Alzheimer type (73%) with vascular lesions (24%) associated with brain tumours (2%) or normal-pressure hydrocephalus (1%). On average, 2 pathologies were associated with Alzheimer's dementia and 3.5 with dementia cum vascular brain lesions. Repeated evaluation of cognitive performance was carried out using Folster's Mini Mental Status (MMS), a global evaluation test. It showed that 18% of the patients were significantly improved while the other diseases were being treated. The hypothesis of regressive confusional elements superimposed on dementia is accepted by the authors as it fits the model of geriatric multipathology morbidity. Since there is no specific treatment for most types of dementia, particular attention must be paid to associated diseases likely to aggravate the clinical expression of dementia.

[Management of large adrenal glands discovered incidentally]. / Conduite à tenir devant les grosses surrénales de découverte fortuite.

Incidental adrenal tumors are more and more often discovered with development of the new radiological techniques (CT scan, sonography). In such an occurrence, the largest panel of adrenal hormones measurements is needed. In the absence of hormonal abnormality, no exam can help for the clinical decision-making. According to epidemiological findings, we propose to operate upon tumors larger than 6 cm and to repeat CT scans at 2, 6 and 18 months for tumors smaller than 6 cm which should be operated upon if an enlargement of the adrenal tumor is demonstrated by a control exam. This attitude relies upon the quite higher frequency of adrenal adenomas (more than 99% of non-functioning adrenal tumors) and the more important risk of malignant adrenal carcinoma in front of a huge tumor. It appears to be the right choice in a cost-effectiveness perspective.

[Renal oncocytoma. Apropos of 9 cases]. / Oncocytome rénal. A propos de neuf cas.

The authors report nine cases of renal oncocytoma which were observed in a series of 220 consecutive renal cell carcinomas. They share the general view concerning the clinical latency of these tumors which are rarely hematuric, and concerning the favorable prognosis, despite signs of locoregional malignancy. On the other hand, they do not share the opinion that arteriography or CT scan can provide a reliable preoperative differential diagnosis with the normal type of renal cell carcinoma.

[Natural history and prognostic factors of superficial tumors of the bladder]. / Histoire naturelle et facteurs pronostiques des tumeurs superficielles de la vessie.

Forty-five patients with superficial bladder cancer managed by transurethral resection alone were studied longitudinally to identify factors associated with progression. Tumor grade, multiple tumor foci, and time to first recurrence were closely correlated with progression. Findings from this study are compared with previous reports. These data are useful to identify patients requiring more aggressive therapy, including intravesical anticancer drugs and BCG, and monitoring with closer-spaced cystoscopies.

[Cystic cancer of the kidney]. / Les cancers kystiques du rein.

Four cases of cystic renal adenocarcinoma in adults free of renal dysfunction are reported. The authors propose a diagnostic approach for atypical cysts that takes the new imaging techniques into account (ultrasonography and CT scan initially, MRI subsequently). A practical therapeutic strategy is also described: because intraoperative histologic diagnosis is difficult partial nephrectomy to allow an intraoperative study of the entire cyst is advocated; extensive nephrectomy, which is the only procedure that ensures total exeresis of the carcinoma, is performed either immediately if the intraoperative study of the cyst or of its aseptic necrotic and hemorrhagic content is positive, or later if subsequent histologic studies reveal a malignancy.

[Pelvic lymphatic excision using laparoscopy. Its value in the staging of tumors of the bladder]. / Curage ganglionnaire pelvien par voie coelioscopique. Intérêt dans le bilan d'extension des tumeurs de vessie.

Laparoscopic surgical procedures are being evaluated in urologic diseases including bladder cancer. Patients with apparently localized tumors may have lymph node involvement indicating disseminated disease for which locoregional treatments are inadequate. Laparoscopic lymphadenectomy may be useful for staging, since neither noninvasive procedures nor intraoperative examination of lymph nodes removed during cystectomy are completely reliable. The technique is described in detail. Benefits in bladder cancer patients remain to be determined.

[The use of monoclonal antibodies in the evaluation of the aggressiveness of tumors of the bladder]. / Apport des anticorps monoclonaux dans l'évaluation de l'agressivité des tumeurs de vessie.

Monoclonal antibodies produced using hybridoma technology have enabled identification of new tumor markers. Targets include tumor-associated antigens, growth factors and their receptors, blood group antigens, cell proliferation antigens, oncogene or tumor suppressor gene products, and markers for drug resistance. Immunohistochemical or flow cytometry studies performed with monoclonal antibodies can be used to determine the immunophenotype of normal and tumoral urothelium; specificity may be primarily for superficial or deep tumors, or for different tumor grades. A number of monoclonal antibodies have been found of prognostic value independently from conventional prognostic criteria. Others have shown diagnostic value. The most promising monoclonal antibodies are reviewed herein.

[Results of treatment of superficial vesical tumors by transurethral resection alone and transurethral resection followed by an intravesical instillation of Calmette-Guerin bacillus]. / Résultat du traitement des tumeurs superficielles de la vessie par résection transuréthrale seule et résection transuréthrale suivie d'instillation endovésicale de bacille Calmette-Guérin.

Superficial bladder tumors treated at the Henri Mondor Hospital from 1984 through 1988 were analyzed for recurrence and progression using the following prognostic parameters: stage (TNM classification, 1978), grade (G1, G2, G3), size, number of tumors, and tumor malignancy index as defined by the Besançon group. Forty-five patients were treated with transurethral resection alone (TUR group) whereas 30 had TUR followed by the prophylactic instillation of fresh Calmette-Guérin bacillus in the bladder (BCG group). In TUR patients, parameters predictive of progression included grade G3, multiple tumors, stage T1, recurrence within 6 months of TUR, and a tumor malignancy index above 455. None of these criteria were predictive of a response to BCG. Results obtained in the BCG group were comparable to those reported in the literature and confirmed the efficacy of BCG instillations to prevent recurrence and progression of superficial carcinomas of the bladder.

[Prognostic value of a positive single ultrasound-guided prostatic biopsy regarding tumor volume and intracapsular nature of prostatic adenocarcinoma]. / Valeur pronostique d'une unique biopsie prostatique échoguidée positive sur le volume tumoral et le caractère intracapsulaire de l'adénocarcinome prostatique.

OBJECTIVE: Study of the value of a single positive prostatic biopsy in the staging of prostatic carcinoma and the significance of the tumour volume. METHOD: The clinical, laboratory and pathological parameters were studied in 27 prostatectomized patients with a single positive prostatic biopsy. RESULTS: The length of tumour invasion on the biopsy was 2.6 mm (evaluation on 25 biopsies). Six patients (23%) had an extracapsular tumour and 21 (78%) had a significant tumour volume. Among the 16 patients with a length of tumour invasion < or = 3 mm, 13 (81%) had a significant tumour volume. 25% of patients with less than 3 mm of invasion on the biopsy and a Gleason score < or = 6 and 12% of patients with less than 3 mm of invasion and a PSA < or = 10 ng/ml had a non-significant tumour volume. CONCLUSION: The presence of a single positive prostatic biopsy is not sufficient to determine the pathological stage of a prostatic carcinoma. In this retrospective study, the majority of patients with a single positive biopsy had a significant tumour volume > 0.5 cc. No preoperative predictive factor of tumour volume was demonstrated.

[Value of biopsies in staging of prostatic cancer before radical prostatectomy]. / Valeur des biopsies dans la stadification du cancer de prostate avant prostatectomie radicale.

The diagnosis of prostate cancer is confirmed by histological examination of prostate biopsies. In cases of localized prostate cancer, in which radical prostatectomy can be proposed as curative treatment, these biopsies, directly reflecting the cancer, can provide important prognostic elements, by specifying the tumour staging, allowing better patient selection and guiding surgical techniques in order to improve the postoperative histological results either by decreasing the number of pT3 tumours (extraprostatic) or the positive resection margin rate. Only pejorative elements are a good indicator of extraprostatic spread of the tumour: a Gleason score greater than 7, the presence of extracapsular invasion, perineural invasion, seminal vesicle invasion, 66% of positive biopsies are in favour of extraprostatic tumour. In contrast, the presence of apparently favourable prognostic elements, such as a low Gleason score, one out of six positive biopsies, limited invasion of biopsies cannot confirm the presence of a minimally aggressive, intraprostatic tumour (pT2). Other prognostic criteria may be discovered in the future, which will confirm with greater precision the extraprostatic or intraprostatic nature of localized prostatic tumours.