Expression of E-cadherin repressors SNAIL, ZEB1 and ZEB2 by tumour and stromal cells influences tumour-budding phenotype and suggests heterogeneity of stromal cells in pancreatic cancer.

BACKGROUND: There is evidence that tumour-stroma interactions have a major role in the neoplastic progression of pancreatic ductal adenocarcinoma (PDAC). Tumour budding is thought to reflect the process of epithelial-mesenchymal transition (EMT); however, the relationship between tumour buds and EMT remains unclear. Here we characterize the tumour-budding- and stromal cells in PDAC at protein and mRNA levels concerning factors involved in EMT. METHODS: mRNA in situ hybridisation and immunostaining for E-cadherin, ß-catenin, SNAIL1, ZEB1, ZEB2, N-cadherin and TWIST1 were assessed in the main tumour, tumour buds and tumour stroma on multipunch tissue microarrays from 120 well-characterised PDACs and associated with the clinicopathological features, including peritumoural (PTB) and intratumoural (ITB) budding. RESULTS: Tumour-budding cells showed increased levels of ZEB1 (P<0.0001) and ZEB2 (P=0.0119) and reduced E-cadherin and ß-catenin (P<0.0001, each) compared with the main tumour. Loss of membranous ß-catenin in the main tumour (P=0.0009) and tumour buds (P=0.0053), without nuclear translocation, as well as increased SNAIL1 in tumour and stromal cells (P=0.0002, each) correlated with high PTB. ZEB1 overexpression in the main tumour-budding and stromal cells was associated with high ITB (P=0.0084; 0.0250 and 0.0029, respectively) and high PTB (P=0.0005; 0.0392 and 0.0007, respectively). ZEB2 overexpression in stromal cells correlated with higher pT stage (P=0.03), lymphatic invasion (P=0.0172) and lymph node metastasis (P=0.0152). CONCLUSIONS: In the tumour microenvironment of phenotypically aggressive PDAC, tumour-budding cells express EMT hallmarks at protein and mRNA levels underlining their EMT-type character and are surrounded by stromal cells expressing high levels of the E-cadherin repressors ZEB1, ZEB2 and SNAIL1, this being strongly associated with the tumour-budding phenotype. Moreover, our findings suggest the existence of subtypes of stromal cells in PDAC with phenotypical and functional heterogeneity.

Trends and outcomes in the use of surgery and radiation for the treatment of locally advanced esophageal cancer: a propensity score adjusted analysis of the surveillance, epidemiology, and end results registry from 1998 to 2008.

We examined outcomes and trends in surgery and radiation use for patients with locally advanced esophageal cancer, for whom optimal treatment isn't clear. Trends in surgery and radiation for patients with T1-T3N1M0 squamous cell or adenocarcinoma of the mid or distal esophagus in the Surveillance, Epidemiology, and End Results database from 1998 to 2008 were analyzed using generalized linear models including year as predictor; Surveillance, Epidemiology, and End Results doesn't record chemotherapy data. Local treatment was unimodal if patients had only surgery or radiation and bimodal if they had both. Five-year cancer-specific survival (CSS) and overall survival (OS) were analyzed using propensity-score adjusted Cox proportional-hazard models. Overall 5-year survival for the 3295 patients identified (mean age 65.1 years, standard deviation 11.0) was 18.9% (95% confidence interval: 17.3-20.7). Local treatment was bimodal for 1274 (38.7%) and unimodal for 2021 (61.3%) patients; 1325 (40.2%) had radiation alone and 696 (21.1%) underwent only surgery. The use of bimodal therapy (32.8-42.5%, P = 0.01) and radiation alone (29.3-44.5%, P < 0.001) increased significantly from 1998 to 2008. Bimodal therapy predicted improved CSS (hazard ratios [HR]: 0.68, P < 0.001) and OS (HR: 0.58, P < 0.001) compared with unimodal therapy. For the first 7 months (before survival curve crossing), CSS after radiation therapy alone was similar to surgery alone (HR: 0.86, P = 0.12) while OS was worse for surgery only (HR: 0.70, P = 0.001). However, worse CSS (HR: 1.43, P < 0.001) and OS (HR: 1.46, P < 0.001) after that initial timeframe were found for radiation therapy only. The use of radiation to treat locally advanced mid and distal esophageal cancers increased from 1998 to 2008. Survival was best when both surgery and radiation were used.

Neoadjuvant chemoradiotherapy with or without panitumumab in patients with wild-type KRAS, locally advanced rectal cancer (LARC): a randomized, multicenter, phase II trial SAKK 41/07.

BACKGROUND: We conducted a randomized, phase II, multicenter study to evaluate the anti-epidermal growth factor receptor (EGFR) mAb panitumumab (P) in combination with chemoradiotherapy (CRT) with standard-dose capecitabine as neoadjuvant treatment for wild-type KRAS locally advanced rectal cancer (LARC). PATIENTS AND METHODS: Patients with wild-type KRAS, T3-4 and/or N+ LARC were randomly assigned to receive CRT with or without P (6 mg/kg). The primary end-point was pathological near-complete or complete tumor response (pNC/CR), defined as grade 3 (pNCR) or 4 (pCR) histological regression by Dworak classification (DC). RESULTS: Forty of 68 patients were randomly assigned to P + CRT and 28 to CRT. pNC/CR was achieved in 21 patients (53%) treated with P + CRT [95% confidence interval (CI) 36%-69%] versus 9 patients (32%) treated with CRT alone (95% CI: 16%-52%). pCR was achieved in 4 (10%) and 5 (18%) patients, and pNCR in 17 (43%) and 4 (14%) patients. In immunohistochemical analysis, most DC 3 cells were not apoptotic. The most common grade ≥3 toxic effects in the P + CRT/CRT arm were diarrhea (10%/6%) and anastomotic leakage (15%/4%). CONCLUSIONS: The addition of panitumumab to neoadjuvant CRT in patients with KRAS wild-type LARC resulted in a high pNC/CR rate, mostly grade 3 DC. The results of both treatment arms exceeded prespecified thresholds. The addition of panitumumab increased toxicity.

Systematic review of atraumatic splenic rupture.

BACKGROUND: Atraumatic splenic rupture (ASR) is an ill defined clinicopathological entity. METHODS: The aim was to characterize aetiological and risk factors for ASR-related mortality in order to aid disease classification and treatment. A systematic literature review (1980-2008) was undertaken and logistic regression analysis employed. RESULTS: Some 632 publications reporting 845 patients were identified. The spleen was normal in 7.0 per cent (atraumatic-idiopathic rupture). One, two or three aetiological factors were found in 84.1, 8.2 and 0.7 per cent respectively (atraumatic-pathological rupture). Six major aetiological groups were defined: neoplastic (30.3 per cent), infectious (27.3 per cent), inflammatory, non-infectious (20.0 per cent), drug- and treatment-related (9.2 per cent) and mechanical (6.8 per cent) disorders, and normal spleen (6.4 per cent). Treatment comprised total splenectomy (84.1 per cent), organ-preserving surgery (1.2 per cent) or conservative measures (14.7 per cent). The ASR-related mortality rate was 12.2 per cent. Splenomegaly (P = 0.040), age above 40 years (P = 0.007) and neoplastic disorders (P = 0.008) were associated with increased ASR-related mortality on multivariable analysis. CONCLUSION: The condition can be classified simply into atraumatic-idiopathic (7.0 per cent) and atraumatic-pathological (93.0 per cent) splenic rupture. Splenomegaly, advanced age and neoplastic disorders are associated with increased ASR-related mortality.

Roux-en-Y drainage of the pancreatic stump decreases pancreatic fistula after distal pancreatic resection.

Clinically relevant fistula after distal pancreatic resection occurs in 5-30% of patients, prolonging recovery and considerably increasing in-hospital stay and costs. We tested whether routine drainage of the pancreatic stump into a Roux-en-Y limb after distal pancreatic resection decreased the incidence of fistula. From October 2001, data of all patients undergoing pancreatic distal resection were entered in a prospective database. From June 2003 after resection, the main pancreatic duct and the pancreatic stump were oversewn, and in addition, anastomosed into a jejunal Roux-en-Y limb by a single-layer suture (n = 23). A drain was placed near the anastomosis, and all patients received octreotide for 5-7 days postoperatively. The volume of the drained fluid was registered daily, and concentration of amylase was measured and recorded every other day. Patient demographics, hospital stay, pancreatic fistula incidence (> or =30 ml amylase-rich fluid/day on/after postoperative day 10), perioperative morbidity, and follow-up after discharge were compared with our initial series of patients (treated October 2001-May 2003) who underwent oversewing only (n = 20). Indications, patient demographics, blood loss, and tolerance of an oral diet were similar. There were four (20%) pancreatic fistulas in the "oversewn" group and none in the anastomosis group (p < 0.05). Nonsurgical morbidity, in-hospital stay, and follow-up were comparable in both groups.

Laparoscopic ventral hernia repair is safe and cost effective.

BACKGROUND: Ventral hernia repair is increasingly performed by laparoscopic means since the introduction of dual-layer meshes. This study aimed to compare the early complications and cost effectiveness of open hernia repair with those associated with laparoscopic repair. METHODS: Open ventral hernia repair was performed for 92 consecutive patients using a Vypro mesh, followed by laparoscopic repair for 49 consecutive patients using a Parietene composite mesh. RESULTS: The rate of surgical-site infections was significantly higher with open ventral hernia repair (13 vs 1; p = 0.03). The median length of hospital stay was significantly shorter with laparoscopic surgery (7 vs 6 days; p = 0.02). For laparoscopic repair, the direct operative costs were higher (2,314 vs 2,853 euros; p = 0.03), and the overall hospital costs were lower (9,787 vs 7,654 euros; p = 0.02). CONCLUSIONS: Laparoscopic ventral hernia repair leads to fewer surgical-site infections and a shorter hospital stay than open repair. Despite increased operative costs, overall hospital costs are lowered by laparoscopic ventral hernia repair.

Cotton-wool exudates not observed in recipients of renal transplants treated with cyclosporine.

Retinal cotton-wool patches, not previously observed in bone marrow recipients, have been reported in three patients who received Sandimmun (cyclosporine) as prophylaxis for graft-versus-host-disease after bone marrow transplantation. These patients all had acute lymphoblastic leukemia and had received, in addition to the standard conditioning regimen, central nervous system irradiation before transplantation. We were thus prompted to examine 55 renal transplant recipients (15 of them prospectively) who were receiving cyclosporine for evidence of similar fundal changes. No cotton-wool patches were found in any of the renal transplant recipients.

Intrathecal levels of complement-derived soluble membrane attack complex (sC5b-9) correlate with blood-brain barrier dysfunction in patients with traumatic brain injury.

It has become evident in recent years that intracranial inflammation after traumatic brain injury (TBI) is, at least in part, mediated by activation of the complement system. However, most conclusions have been drawn from experimental studies, and the intrathecal activation of the complement cascade after TBI has not yet been demonstrated in humans. In the present study, we analyzed the levels of the soluble terminal complement complex sC5b-9 by ELISA in ventricular cerebrospinal fluid (CSF) of patients with severe TBI (n = 11) for up to 10 days after trauma. The mean sC5b-9 levels in CSF were significantly elevated in 10 of 11 TBI patients compared to control CSF from subjects without trauma or inflammatory neurological disease (n = 12; p < 0.001). In some patients, the maximal sC5b-9 concentrations were up to 1,800-fold higher than in control CSF. The analysis of the extent of posttraumatic blood-brain barrier (BBB) dysfunction, as determined by CSF/serum albumin quotient (Q(A)), revealed that patients with a moderate to severe BBB impairment (mean Q(A) > 0.01) had significantly higher intrathecal sC5b-9 levels as compared to patients with normal BBB function (mean Q(A) < 0.007; p < 0.0001). In addition, a significant correlation between the individual daily Q(A) values and the corresponding sC5b-9 CSF levels was detected in 8 of 11 patients (r = 0.72-0.998; p < 0.05). These data demonstrate for the first time that terminal pathway complement activation occurs after head injury and suggest a possible pathophysiological role of complement with regard to posttraumatic BBB dysfunction.

Interleukin-10 reduces the systemic inflammatory response in a murine model of intestinal ischemia/reperfusion.

BACKGROUND: Intestinal ischemia/reperfusion (I/R) is known to increase systemic cytokine levels, as well as to activate neutrophils in distant organs. This study was designed to investigate the effect of interleukin-10 (IL-10) on cytokine release, pulmonary neutrophil accumulation, and histologic changes in a murine model of I/R. METHODS: Forty female Swiss-Webster mice were divided into four groups. Group 1 underwent 45 minutes of superior mesenteric artery occlusion followed by 3-hour reperfusion (I/R). Group 2 underwent laparotomy alone (Sham). Group 3 underwent I/R, but was treated with IL-10, 10,000 units IP every 2 hours, starting 1 hour before reperfusion (Pretreatment). Group 4 was treated with an equal dose of IL-10, starting 1 hour after reperfusion (Posttreatment). All animals were killed at 3 hours, standard assays were performed for serum cytokine levels, and lung myeloperoxidase activity and intestinal histology were scored. RESULTS: Serum cytokines (TNF-alpha and IL-6), lung myeloperoxidase levels, and histologic score were significantly reduced when IL-10 was administered either before or after reperfusion. CONCLUSIONS: IL-10 reduced the severity of local and systemic inflammation in a murine model of intestinal I/R when given before or after reperfusion injury. These observations suggest that IL-10 may exert its effect by blocking cytokine production and distant organ neutrophil accumulation.

An ETa/ETb endothelin antagonist ameliorates systemic inflammation in a murine model of acute hemorrhagic pancreatitis.

BACKGROUND: Endothelin peptides are polykines with strong vasoconstrictor properties. We have previously shown that endothelin antagonism (PD145065) reduces the local severity of acute pancreatitis. We now investigated the effect of endothelin antagonism on systemic inflammation in a model of acute hemorrhagic pancreatitis. METHODS: Forty-two mice were divided into four groups. Group 1 was fed standard food plus PD145065 every 8 hours. Group 2 was fed a choline-deficient ethionine (CDE) supplemented diet and given saline every 8 hours. Group 3 was fed a CDE diet and treated with PD145065 every 8 hours from initiation of diet. Group 4 was fed a CDE diet and given PD145065 from 48 hours after initiation of diet. Animals were killed at 70 hours. Serum was collected. Pancreata and lung tissue were harvested. RESULTS: Histology score, serum amylase level, lung myeloperoxidase, and interleukin (IL)-10 were all significantly reduced in both treatment groups (groups 3 and 4) (p < 0.05). IL-6 levels were reduced in group 3 only (p < 0.05). The mortality rate did not differ among any of the groups. CONCLUSIONS: Endothelin antagonism decreased the severity of acute pancreatitis and reduced markers of systemic inflammation. Late treatment at 48 hours failed to prevent the rise in IL-6. Mortality rates were unaffected by treatment.

Primary duodenal adenocarcinoma: a 40-year experience.

HYPOTHESIS: In patients with duodenal adenocarcinoma, certain pathologic features of the tumor will have prognostic significance. DESIGN: Retrospective case series. PATIENTS: Forty-nine patients diagnosed with duodenal adenocarcinoma between 1957 and 1998. RESULTS: The tumors of 31 (63%) of the 49 patients underwent resection, 18 (37%) had surgical palliation or underwent biopsy. Mean (+/- SEM) survival for all patients was 49 +/- 9 months. The patients whose tumors were resected had longer survival than those who underwent palliation (mean +/- SEM, 66 +/- 13 months vs 18 +/- 6 months, P =.02). Multivariate analysis revealed large tumor size (P =.01), transmural invasion (P =.004), and moderate to poor tumor grade (P =.03) were negatively correlated with survival. Lymph node status did not influence survival. CONCLUSIONS: Our 40-year experience with duodenal adenocarcinoma demonstrates that large tumor size, advanced histological grade, and transmural invasion are associated with decreased survival. These results underscore the importance of early diagnosis, and suggest the presence of nodal spread is not a contraindication to resection.

Pancreatic infection in severe pancreatitis: the role of fungus and multiresistant organisms.

HYPOTHESIS: Recent controlled clinical studies suggest a positive effect of early antibiotic treatment on late morbidity and mortality in severe acute pancreatitis. However, widespread use of antibiotics may lead to an increased number of fungal infections and multiresistant bacteria, thereby worsening the outcome of the disease. DESIGN: Single-center prospective study. SETTING: University hospital, gastrointestinal surgical service. PATIENTS: One hundred three patients with necrotizing pancreatitis seen consecutively in our service. INTERVENTIONS: In addition to standard treatment, patients with proven necrotizing pancreatitis received a prophylactic intravenous antibiotic treatment. Pancreatic infection was regarded as an indication for surgery. MAIN OUTCOME MEASURES: Pancreatic infection, microbiological findings, drug resistance, fungal infections. RESULTS: Thirty-three patients (32%) had infected necrosis. Gram-negative organisms were isolated from 19 patients (58%), Gram-positive organisms were isolated from 18 patients (55%), fungal organisms were isolated from 8 patients (24%), and multiresistant organisms were isolated from 3 patients (9%). In 7 patients (21%), the organisms cultured from the pancreatic tissue were resistant to the antibiotics given in for prophylaxis. Infection with multiresistant organisms or organisms resistant to the antibiotic used for prophylaxis, but not with fungal infection or Gram-positive or Gram-negative infection, was correlated with a negative outcome. CONCLUSIONS: Fungal infection under adequate treatment is not associated with a negative outcome. The occurrence of multiresistant organisms seems to be a rare finding (3 of 103 patients). Antibiotic prophylaxis is effective in preventing infection in necrotizing pancreatitis, but optimal choice and duration of administration of the antibiotic agent(s) need to be carefully determined to avoid the sequelae of multiresistant organisms.

Kupffer cell blockade reduces hepatic and systemic cytokine levels and lung injury in hemorrhagic pancreatitis in rats.

Severe acute pancreatitis (AP) is associated with both the local (pancreatic) release of cytokines and an elevation in their systemic plasma concentrations. This may lead to organ dysfunction and death of the patient. The aims of this study were to investigate the source(s) of systemic cytokine production during experimental AP. Forty-two rats were allocated to five groups (control, sham operation and saline injection, sham operation and gadolinium chloride injection, intraductal sodium-taurocholate infusion and saline injection, or intraductal sodium-taurocholate infusion and gadolinium chloride injection). Blood from the iliac artery, portal vein, and hepatic vein, along with tissue from the pancreas, liver, and lung, were collected. Serum levels of TNFalpha, IL-1beta, IL-6, and IL-10 were determined by enzyme-linked immunosorbent assay. Tissue mRNA for IL-1beta and IL-10 was assessed by reverse-transcription polymerase chain reaction. In untreated animals with AP, the lowest serum cytokine levels were found in the portal vein. In the hepatic vein, the levels of TNFalpha, IL-1beta, and IL-6 were higher. The highest serum levels were detected in the systemic circulation. In the gadolinium chloride-treated group, there was no increase in hepatic or systemic cytokine levels and less lung injury was observed. Extrapancreatic cytokine production from both the liver and the lung contributed significantly to systemic levels of TNFalpha, IL-1beta, IL-6, and IL-10 in this experimental model of AP.

International Federation of Ophthalmological Societies statutes and regulations.

PURPOSE: To provide an understanding of the structure, role, and responsibility of the International Federation of Ophthalmological Societies, the International Council of Ophthalmology, and the International Congress of Ophthalmology. These established entities have recently codified their statutes and regulations and registered them in Zurich, Switzerland. METHODS: The International Council of Ophthalmology, which serves as the executive body of the International Federation of Ophthalmological Societies, used historical operating documents to prepare the statutes and regulations, which were reviewed and adopted by the International Federation of Ophthalmological Societies at the 28th International Congress of Ophthalmology in Amsterdam on June 23, 1998. RESULTS: The statutes and regulations of the International Federation of Ophthalmological Societies, the International Council of Ophthalmology, and the International Congress of Ophthalmology are available to supranational ophthalmological organizations, national ophthalmological societies, other ophthalmological organizations, and individual ophthalmologists. CONCLUSIONS: The statutes and regulations of the International Federation of Ophthalmological Societies, the International Council of Ophthalmology, and the International Congress of Ophthalmology provide a basis for an organizational structure in international ophthalmology. The International Congress of Ophthalmology, first held in 1857, is the longest continuing international meeting in medicine. The International Council of Ophthalmology was established in 1927, and the International Federation of Ophthalmological Societies was formed in 1933. These organizations coordinate the International Congress of Ophthalmology, which convenes with the International Federation of Ophthalmological Societies every 4 years. The International Council, as the executive body, meets annually. The International Council of Ophthalmology has for decades worked to coordinate and facilitate interchange, education, and standards in international ophthalmology. Currently, the International Council of Ophthalmology, working with other international organizations, is creating an international ophthalmology strategic plan, which includes focus on ophthalmic training, continuing education, advocacy for the preservation and restoration of vision, clinical guidelines, and research.

Resection of locally advanced pancreatic cancer after downstaging with continuous-infusion 5-fluorouracil, mitomycin-C, leucovorin, and dipyridamole.

Patients with locally advanced pancreatic adenocarcinoma who receive conventional therapy with radiation with 5-fluorouracil (5-FU) have median survivals ranging from 8 to 12 months. Here we report our experience with a four-drug chemotherapeutic regimen that resulted in sufficient downstaging of tumor in some patients to justify surgical reexploration and resection. From April 1991 through April 1994, 38 patients received 5-FU as a continuous infusion (200 mg/m2/day), calcium leucovorin weekly by intravenous bolus injection (30 mg/m2), mitomycin-C every 6 weeks (10 mg/m2 intravenously), and dipyridamole daily orally (75 mg) for locally advanced unresected pancreatic cancer. All of these patients were evaluable for response, toxicity, and survival. There were 14 partial responses and one complete response--a 39% response rate. The median survival for all patients was 15.5 months; the 1-year survival rate from time of initial diagnosis was 70%. Six of 15 responding patients had sufficient tumor regression to meet clinical criteria for resectability and reexploration, four of whom underwent a curative resection. The median survival of these six patients was 28 months from the time of original diagnosis. The 1-year survival was 83%, with one patient still alive and free of disease at 53 months. We believe this unique experience from a single institution justifies a prospective multi-institutional trial to evaluate the efficacy of this approach in a larger number of patients.

Hepatic Kupffer cell blockade reduces mortality of acute hemorrhagic pancreatitis in mice.

Inflammatory cytoklines derived from the liver may cause distant organ failure and death in severe pancreatitis. To minimize liver cytokine release, we studied the effects of Kupffer cell blockade on the mortality rate and severity of inflammation in a model of that disease. Thirty mice were divided into three groups. Group I received gadolinium chloride (l mg/100 g intravenously), which blocks Kupffer cell activity, and regular food. Groups 2 and 3 were fed a choline-deficient, ethionine-supplemented diet and developed severe pancreatitis. Group 2 (control) received intravenous saline solution, and group 3 received gadolinium chloride. Animals were killed at 72 hours. Serum levels of tumor necrosis factor-alpha and interleukin-1Beta, interleukin-6, and interleukin-10 were determined by enzyme-linked immunosorbent assay. Lung neutrophil infiltration was assessed by myeloperoxidase assay. Pancreatic inflammation was scored in a blinded manner. In a separate experiment, mortality rates were determined in saline- and gadolinium-treated animals (n=100). Gadolinium reduced the levels of all the cytoklines and lung myeloperoxidase (P<0.05). Gadolinium also reduced the mortality rate (52% vs. 86%; P <0.001). However, the degree of pancreatic inflammation was unchanged by gadolinium treatment. These data support the hypothesis that mortality in severe pancreatitis may in part be related to the secondary release of hepatic cytokines.

Long-term fluctuations versus actual field loss in glaucoma patients.

In following glaucomatous visual fields with automated perimetry, one becomes aware of the difficulty in differentiating between long-term fluctuations and actual changes. We have analyzed visual fields of one randomly selected eye of each of 34 patients (mean age = 61.8 +/- 12.3 years) with proven glaucoma chronicum simplex and at least 4 (mean = 5.6 +/- 1.9) visual field examinations with programs 31 and/or 33 of the Octopus 201 within at least 21 months (mean = 32.6 +/- 6 months). When a group of earlier visual fields is compared with a group of later ones utilizing the statistical program delta-change, the results of regression analysis, based on data from program delta-series, are juxtaposed to the results of the t test with very good correlation. This investigation confirms that glaucomatous visual fields exhibit considerable long-term fluctuations; as long as field loss and gain observed over a longer time period are evenly distributed, the symmetrical portions of the distribution curve may serve as the outer limits of long-term fluctuation. In this regard, definite visual field deterioration was discerned in none of our medically treated patients over an average observation period of 32 months. If more selective criteria for differentiating between long-term fluctuations and actual field change are used (such as measurement of long-term fluctuations performed in earlier investigations, the t test of program delta-change, regression analysis of the data produced by program delta-series, as well as the correspondence between the t test and the correlation coefficient of the regression analysis), 3 eyes have changed for the worse regarding loss per test location, and 3 have changed for the worse regarding sensitivity.

Cell cycle time and life-span of cells in the mouse eye. Measurements during the postfetal period using repeated 3H-thymidine injections.

In this investigation the cell cycle time and the life-span of cells in different tissues of the mouse eye were determined during postfetal development not with single but, instead, by means of repeated 3H-thymidine injections. The potential of this method applied for the first time in the mammalian eye, is thoroughly discussed. Essentially, four groups of 19-21 mice each, aged 1, 10, 20, and 60 days at the start of the experiment, received intraperitoneal injections of 3H-thymidine at a dose of 1 microCi/g body weight every 4 h for a maximum of 14 days, i.e. a total of up to 85 injections. Further animals were sacrificed after the 13th, 19th, 25th, 31st, 37th, 49th, 61st, 73rd, and 85th injections, i.e. 2, 3, 4, 5, 6, 8, 10, 12, and 14 days after the start of the experiment. When all the injections had been given, animals from each group were sacrificed on the 1st, 4th, 8th, 16th, and sometimes the 32rd, 48th, and 64th days, respectively, after the last injection. With this experimental paradigm it was possible: (1) to determine the cell cycle time and the life-span of the cells during postfetal development up to maturity without gaps; (2) to establish the end of the development by means of cell proliferation in various tissues of the mouse eye; herewith it was possible to determine the times at which the development by cell proliferation is replaced by development by cell differentiation, and (3) to clearly prove in which mature ocular tissues cell turnover still exists and in which it does not; this appears to be especially important, since in recent years the importance of cell proliferation process following injury and stimulation was also recognized in the eye, for example, in massive periretinal proliferation in connection with retinal detachment and retinal surgery, as well as in endothelial injuries following intraocular lens implantation; only when normal conditions are known can pathological proliferative processes be recognized as such and be distinguished from normal ones. The results are cumulatively represented in tabular form, from which details are to be extracted. As expected, cell cycle times are very short and seemingly homogeneous in tissues which develop within themselves, but become longer and inhomogeneous, except in the inner and outer granular layer of the retina, in which the cell proliferation comes to a particularly abrupt end. The shortest cell cycle time occurred in the cells of the vascular walls of the retina at the time of birth and was 24 h.(ABSTRACT TRUNCATED AT 400 WORDS)

Membrane formation in the chamber angle after failure of argon laser trabeculoplasty: analysis of risk factors.

AIM: Membrane formation in the chamber angle induced by argon laser trabeculoplasty (ALT) can be a cause of treatment failure. Identification of risk factors for membrane formation was the primary aim of this retrospective study. METHODS: Semithin sections of trabeculectomy specimens obtained in a 2 year period were examined by light microscopy. 122 eyes which were treated with one or more ALTs before trabeculectomy were identified. In 46 eyes, a sufficient amount of trabecular meshwork was obtained to permit morphological analysis. RESULTS: Eyes treated with ALT had a significantly higher incidence of membrane formation (p=0.001). In 23/46 specimens a cellular and collagenous membrane was observed covering the entire trabecular meshwork. In 14/23 specimens (61%), this membrane was readily visible at low power magnification (x40). Comparison of these eyes with those without membrane formation revealed a significant difference in the number of ALTs (mean 2.07 (SD 0.73) v 1.48 (0.59); p=0.026) and in preoperative IOP (32.0 (9. 7) v 26.2 (8.4) mm Hg; p=0.04). CONCLUSIONS: Membrane formation in the chamber angle is a frequent cause of ALT failure. The major risk factor is the number of ALTs performed.