[Intravitreal methotrexate for treatment of uveitic cystoid macular edema]. / Intravitreales Methotrexat zur Behandlung eines uveitisch bedingten zystoiden Makulaödems.

We present the case of a patient who had several intravitreal methotrexate injections due to a uveitic macular edema and a known steroid response. An earlier off-label therapy with avastin had not been successful. After the intravitreal methotrexate injections a good resorption of the retinal fluid as well as a good intraocular pressure and a good visual acuity could be achieved. Visual acuity was limited by pre-existing glaucomatous optic nerve atrophy and a central scar in the cornea.

SFPQ associates to LSD1 and regulates the migration of newborn pyramidal neurons in the developing cerebral cortex.

The development of the cerebral cortex requires the coordination of multiple processes ranging from the proliferation of progenitors to the migration and establishment of connectivity of the newborn neurons. Epigenetic regulation carried out by the COREST/LSD1 complex has been identified as a mechanism that regulates the development of pyramidal neurons of the cerebral cortex. We now identify the association of the multifunctional RNA-binding protein SFPQ to LSD1 during the development of the cerebral cortex. In vivo reduction of SFPQ dosage by in utero electroporation of a shRNA results in impaired radial migration of newborn pyramidal neurons, in a similar way to that observed when COREST or LSD1 expressions are decreased. Diminished SFPQ expression also associates to decreased proliferation of progenitor cells, while it does not affect the acquisition of neuronal fate. These results are compatible with the idea that SFPQ, plays an important role regulating proliferation and migration during the development of the cerebral cortex.

[Intravitreal ranibizumab for the treatment of retinal angiomatous proliferation]. / Intravitreales Ranibizumab für die Behandlung von retinalen angiomatösen Proliferationen.

BACKGROUND: Retinal angiomatous proliferations (RAP) are a subgroup of exsudative or "wet" age-related macular degeneration (wAMD) with devastating reduction of visual acuity in later stages. Intravitreal ranibizumab provides good therapy, but is considered to be less effective than in other choroidal neovascularizations (CNV). OBJECTIVE: We investigated the efficacy of ranibizumab in late-stage III RAP with retinochoroidal anastomosis compared to the outcome of other CNV lesions. MATERIALS AND METHODS: The data of all patients with wAMD treated with ranibizumab were retrospectively analyzed. Patients were divided into groups depending on the lesion type into RAP (identified and selected clinically, proven by fluorescein angiography) and CNV lesions (identified by fluorescein angiography only) named occult, minimally and predominantly classic groups. The best-corrected visual acuity (BCVA) was obtained before (at the timepoint "diagnosis"), during (1st, 2nd, and 3rd injection), and after upload ("1st control"). RESULTS: Before first injection, visual acuity decreased in all groups (0.73 to 0.78 logMAR for all CNV, 0.95 to 1.02 logMAR for RAP). During upload there was no further decline in visual acuity but no improvement as well up to the 1st control visit in the RAP group (1.02 to 1.03 logMAR), but a statistically significant increase in all other groups (0.78 to 0.67 logMAR). CONCLUSION: Treatment of late-stage III RAP with ranibizumab is effective. Stabiliziation of visual acuity can be achieved, but-in contrast to other forms of CNV lesions-no further improvement. Therefore, patients with this special form need to be identified and treated as early as possible.

A Demonstration Project in New York and Virginia: Retrofitting Cost-Effective Roll-over Protective Structures (CROPS) on Tractors.

The NIOSH cost-effective roll-over protective structure (CROPS) demonstration project sought to determine whether three prototype roll-over protective structures (ROPS) designed to be retrofitted on Ford 8N, Ford 3000, Ford 4000, and Massey Ferguson 135 tractors could be installed in the field and whether they would be acceptable by the intended end users (farmers). There were a total of 50 CROPS. demonstrators (25 in New York and 25 in Virginia), with 45 observers attending the New York CROPS demonstrations and 36 observers attending the Virginia CROPS demonstrations, for a total of 70 participants in New York and 61 in Virginia. The oldest retrofitted tractors were 77 to 62 years old, while the newest retrofitted tractors were 40 to 37 years old. The most frequently retrofitted tractor in the CROPS demonstration project was a Ford 3000 series tractor (n = 19; 38%), followed by Ford 4000 (n = 11; 22%), Massey Ferguson 135 (n = 11; 22%), and Ford 8N (n = 9; 18%). A major issue of CROPS retrofitting was the rear wheel fenders. The effort involved in disassembling the fenders (removing the old bolts was often faster by cutting them with a torch), modifying the fender mounting brackets, and then reinstalling the fenders with the CROPS generally required the most time. In addition, various other semi-permanent equipment attachments, such as front-end loaders, required additional time and effort to fit with the CROPS. Demonstrators were asked to rank the reasons why they had not retrofitted their tractors with ROPS until they had enrolled in the CROPS demonstration program. ROPS "cost too much" was ranked as the primary reason for participants in both states (80% for New York and 88% for Virginia). The second highest ranked reasons were "ROPS wasn't available" for Virginia (80%) and "hassle to find ROPS" for New York (69%). The third highest ranked reasons were "not enough time to find ROPS" for New York (67%) and "hassle to find ROPS" for Virginia (79%). All demonstrators and observers indicated that they were glad to have participated in the CROPS project.

Development of kidney scars after acute uncomplicated pyelonephritis: relationship with clinical, laboratory and imaging data at diagnosis.

BACKGROUND: Acute pyelonephritis is a potential cause of kidney scars. AIM: To evaluate the relationship between clinical, laboratory and imaging data and the development of kidney scars in acute pyelonephritis. METHODS: All consecutive patients hospitalized for acute uncomplicated pyelonephritis in our nephrology unit from June 1996 to June 2004 were considered: 58 females, median age 25.6 years (16-52). Diagnosis of pyelonephritis required parenchymal lesions shown by CT or NMR scan. RESULTS: The lesions were bilateral in 17.2% (10/58) patients, unilateral, but multifocal in 81.0% (47/58); at CT or NMR, 65.5% of the lesions were classified as simple, 19% with tendency to colliquation and 15.5% abscessual. The median interval between first symptoms and diagnosis was 5 days (1-25); at referral, only 20.7% had a positive urine culture and 94.8% (55/58) had undergone previous antibiotic treatment. The therapeutic protocol required intravenous therapy for > or = 2 weeks, followed by 2-4 weeks of oral therapy. At 6-8 months, the prevalence of kidney scars was 29.3%. Their development was highly correlated with the type of lesions at diagnosis (highest risk with abscessual lesions; uni- and multivariate analysis). No other clinical or laboratory marker (age, fever, positive cultures, levels of acute phase reactants, interval between onset and diagnosis) was correlated with the outcome (scars). CONCLUSIONS: The type of lesion at diagnosis of acute uncomplicated pyelonephritis is highly correlated with the development of kidney scars. Further studies are needed to test the therapeutic schedules tailored according to the imaging data.

[Verrucous carcinoma of the anus or Buschke-Lowenstein tumor of the anus: staging and treatment. Report of 3 cases]. / Il carcinoma verrucoso dell'ano o tumore di buschke-lowenstein dell'ano: stadiazione e trattamento presentazione di 3 casi.

INTRODUCTION: Giant condyloma acuminatum or Buschke Lowenstein tumor of the anorectal and perianal regions is an uncommon entity that commonly affects genitalia. These are slow-growing, expansive, cauliflower-like, destructive lesions that could propagate to vulvar and vaginal region, rectum and bladder. The hallmark of the disease is the high rate of recurrence (66%) and malignant transformation (56%). No distant metastases usually occur. The median number of recurrences are 2 (range, 1-7). MATERIALS AND METHODS: At the Oncological Surgical Department, University of Turin, three patients were diagnosed with a Buschke Lowenstein tumor. In two cases immunodeficiency was evidentiated (HIV in one case and ciclosporin treatment in the second one). The lesions were up to 15 cm of diameter and in one case scrotum was invaded. In another case a lesion in sacral region was observed. All patients were studied with anoproctoscopy, CT scan, pelvic magnetic resonance and lymphoscintigraphy for following biopsy of inguinal sentinel node for potential malignancy. All patients were submitted to extensive local surgical treatment. RESULTS: No mortality was observed. In one case we observed a late anal stenosis treated with local dilatations. No more complications were observed. One patient with a small persistence of the disease was treated with cryotherapy. All inguinal nodes revealed negative to definitive histological exam, that confirmed the diagnosis of Buschke Lowenstein tumor of the primary lesion. CONCLUSIONS: Buschke Lowenstein tumors are rare but extensive lesions difficult to treat. Local surgery with elettrocautery or laser is the first treatment of choice, even if abdominoperineal amputation sec. Miles could be considered in case of extremely extensive lesions or multiple and extensive recurrences. Others treatments proposed are radiotherapy, chemotherapy, interferon, iniquimod and so on. Other studies are requested to value the best treatment.

p53 analysis of laryngeal cancer in exon 4 to 9.

p53 gene mutations are a common genetic alteration in human cancer and codon 72/exon 4 polymorphism of the p53 gene has been implicated in cancer risk. Therefore in this study the p53 gene status of 32 shock-frozen tumor specimens from larynx carcinomas was analyzed by PCR and sequencing of exon 4 through 9. Four mutations (12.5%) in exon 5, 7, 8 and 9 were detected in the carcinoma specimen. Analysis of codon 72 revealed in eight cases a homozygosity for proline (CCC) and in 24 cases heterozygosity or homozygosity for arginine (CGC). The group with the proline/proline genotype had a median age 10.3 years lower than the remaining patients and included the only two non-smokers. Firstly, these results confirm the p53 mutational status of laryngeal cancer without any clinical correlation and secondly may suggest an oncogenic potential for the proline/proline genotype of codon 72 for laryngeal cancer as has already been assumed for lung cancer.

Cyfra 21-1: a serological help for detection of distant metastases in head and neck cancer.

Local and neck recurrences of squamous cell carcinoma of the head and neck (SCCHN) can mostly be detected early when the patient has regular follow-ups. Distant metastases though usually remain undiscovered until they produce clinical symptoms. Since Cyfra 21-1 correlates with the tumor size and stage in SCCHN, we looked for possible connections between Cyfra 21-1 increases and the development of distant metastases. The sera of 830 patients with SCCHN were tested for Cyfra 21-1. The levels were compared with the clinical run of the patients. When Cyfra 21-1 levels rose above the threshold of 3.3 ng/ml (71 out of 830) staging procedures were performed. Tumor growth was found in 50 out of 71 patients with elevated Cyfra levels (70.4%). Cyfra serum levels in those cases either represented development of distant metastases (27 out of 71), or local and neck recurrences. The results of this study show that Cyfra 21-1 is a suitable and helpful serological parameter for the follow-up of patients with SCCHN. In the event of an elevation of Cyfra 21-1 above the threshold during follow-up, we would recommend the performance of a thoracal CT-scan and abdominal omi ultrasound as staging procedures.

Serum p53 autoantibodies in the follow-up of head and neck cancer patients.

p53 autoantibodies (AAB) are a fairly new serological parameter in patients with malignancies. Although the actual mechanism of how they develop is still unclear, it seems that these AAB could be of prognostic relevance. Very few studies demonstrated the usefulness of p53 AAB in the follow-up of cancer patients. In this study, 109 patients with head and neck cancer were investigated using an ELISA for the presence of p53 AAB in their serum and were followed-up for at least 36 months. In 21 of the cancer patients, p53 serum AAB were detected. In 5/21 p53-seropositive AAB patients, a correlation with the clinical course was observed. Sixteen of the p53-positive patients did not show any significant AAB titer changes during the follow-up, and no significant correlation with the clinical course was seen. According to these results, the clinical value of p53 AAB in the follow-up of patients with head and neck cancer seems to be limited.

Transcriptional repression of the human galactocerebrosidase gene in squamous cell carcinomas of the larynx.

Alterations of gene expression in squamous cell carcinoma (SCC) cell lines derived from the larynx and keratinocytes derived from adjacent normal mucosa of the larynx have been studied using the mRNA differential display technique. Lane-to-lane comparison of reverse transcribed mRNA showed a strong repression of a 148 bp fragment in SCC cells. The fragment was reamplified and cloned. Sequencing revealed a 99.3% homology with a region in exon 17 of the human galactocerebrosidase (GALC) gene. Northern blot analysis confirmed the differential expression of this gene in both carcinoma cell lines and laryngeal SCC biopsies in contrast with corresponding normal mucosa. To provide further evidence for the differential expression rate, both types of cells were transiently transfected with a 152 bp (-176 to -24) high regulatory promoter element of the 5' flanking region of the GALC gene. Results of 3 independent transfection experiments indicated a 16-fold repression of the GALC gene expression in SCC cells compared with benign keratinocytes. However, neither mutation nor other alterations of the promoter sequence were detected. Expression of the GALC gene is thus greatly affected in SCCs of the larynx.

A new prognostic indicator for head and neck cancer--p53 serum antibodies?

BACKGROUND: p53 antibodies are a new serological parameter of unknown potential in patients with malignancies. Their occurrence has been described in various types of cancer patients and several studies in head and neck cancer patients and other cancer patient groups have indicated its prognostic value. MATERIAL AND METHODS: We investigated the incidence of p53 serum antibodies in 271 head and neck cancer patients with an ELISA and investigated a possible correlation with clinical parameters like tumor staging and grading. RESULTS: Sixty-seven head and neck cancer patients (24.7%) were seropositive for p53 antibodies. No correlation between p53 antibody status, tumor staging and grading was found. CONCLUSIONS: These results indicate that the occurrence of p53 antibodies does not correlate with the most relevant prognostic factors, rate of regional metastasis and primary tumor size, in patients with head and neck cancer.

CYFRA 8/18 in head and neck cancer.

BACKGROUND: Cytokeratins (Ck) 8, 18 and 19 that are normally expressed in head and neck tissue in only small amounts, become overexpressed in head and neck squamous cell cancerous tissue. It was questioned whether Ck 8 and 18, which occur together, were also detectable and of value as a tumor markers for this cancer entity. MATERIALS AND METHODS: One hundred forty-nine sera from patients with squamous cell carcinoma of the head and neck (SCCHN) were investigated with a novel ELISA kit for the detection of fragments of Ck 8 and 18. Twenty-five sera from healthy volunteers and 39 patients with benign diseases of the head and neck region served as controls. RESULTS: It was found that CYFRA 8/18 had a sensitivity of 7%. CYFRA 8/18 values did not show a correlation with clinical parameters. CONCLUSIONS: Because of a low sensitivity CYFRA 8/18 seems not to be of value as a tumor marker for SCCHN.

The influence of differing dissection techniques on p53 as a possible indicator for local recurrences in carcinomas of the upper aerodigestive tract.

BACKGROUND: A correlation between the occurrence of p53 protein in margins after tumor resection has been proposed as indicator for recurrence. This study should clarify whether differences occur in p53 protein detection after laser surgery as opposed to surgery with the scalpel. MATERIAL AND METHODS: Healthy mucosa of the oropharynx (n = 28) and squamous cell carcinoma of the head and neck (SCCHN) (n = 19) were excised with scalpel, CO2 and Nd:YAG laser and then examined for the presence of p53 protein with immunohistochemistry and ELISA. RESULTS: The occurrence of p53 protein in SCCHN was dependent on the applied resection technique. In lasersurgically excised tissue only a small zone adjacent to the cutting edge was found to be negative for p53. This zone of necrosis was smaller in margins after CO2 than after Nd:YAG laser resection. CONCLUSIONS: Lasersurgical excision does only inhibit the detection of p53 in the zone of necrosis.

Pulses of soil phosphorus availability in a Mexican tropical dry forest: effects of seasonality and level of wetting.

Intact cores from the upper soil profile and surface litter were collected at the peak of the dry season and during the rainy period in the tropical deciduous forest of the Chamela region, Jalisco, México, to (1) analyze upper soil phosphorus (P) movement and retention, (2) compare soil P dynamic pools (soluble, bicarbonate, and microbial) in dry and rainy seasons, and (3) determine the response of these P pools to wetting. Unperturbed litter-soil cores were treated in the laboratory with either 10 mm or 30 mm of simulated rain with carrier-free 32P and compared to a control (no water addition) to determine the fate and retention of added P. 31P concentrations and pools in most litter and soil fractions were higher in the dry than in the rainy season. Soluble P was 0.306 g/m2 and microbial P was 0.923 g/m2 in the dry season (litter plus soil) versus 0.041 (soluble) and 0.526 (microbial) g P/m2 in the rainy season. After water addition, rainy-season cores retained 99.9 and 94% of 32P in the 10- and 30-mm treatments, respectively. Dry-season samples retained 98.9 and 80% of inputs in the same treatments. Retention after wetting occurred mostly in soil (bicarbonate and microbial fractions). Simulated rainfall on rainy-season soils increased P immobilization. On the other hand, simulated rainfall on dry-season soils released P through mineralization. The P release represents between 46 and 99% of the annual litterfall return. Our results suggest that both soluble and microbial P constitute important sources for initiation of plant growth at the onset of the rainy season in tropical dry forest.

Head and neck cancer and p53-immunogenicity.

BACKGROUND: p53-mutations are of major importance in the development of human malignancies and occur frequently in head and neck cancer. The detection of serum p53-antibodies has been performed for a number of different cancers. For head and neck cancer though, the occurrence of serum p53-antibodies has not been determined so far. MATERIALS AND METHODS: A set of 82 sera from patients with squamous cell carcinomas of the head and neck were screened for circulating antibodies against p53 with ELISA. RESULTS: Of 82 patients 22% (n = 18) demonstrated p53-antibodies in their sera; the specificity for malignancy was 100%. CONCLUSIONS: As far as we know, this is the first study to reveal p53-antibodies in the sera of patients with SCCHN. The high incidence of positivity for p53-antibodies in this subset of cancer patients may give additional help in the diagnosis of this often disfiguring disease.

p53 serum antibodies as prognostic indicator in head and neck cancer.

p53 antibodies are a new serological parameter of unknown potential in patients with malignancies. Their occurrence has been described in various types of cancer patients. The mechanism underlying the immunization process is still unclear. We investigated the incidence of p53 serum antibodies in 143 head and neck cancer patients with an enzyme-linked immunosorbent assay. The posttherapy course of two matched study groups (n = 38 each), one p53-antibody-seropositive and one p53-antibody-seronegative, was followed up for 24 months. Thirty-nine head and neck cancer patients (27.3%) were seropositive for p53 antibodies. During the follow-up, the p53-antibody-seropositive patients accounted for more local tumor recurrences (n = 12 versus n = 8) and more tumor-related deaths (n = 11 versus n = 5) than did seronegative patients, and second primary tumors (n = 9 versus n = 0) occurred exclusively in seropositive patients. In total, therapy failures (recurrences, tumor-related deaths, second primaries) were observed in 17/38 cases (44.7%) in the p53-antibody-seropositive group and in 8/38 cases (21.1%) in the p53-antibody-seronegative group. These results, after a follow-up of 2 years, seem to indicate a prognostic value of p53 serum antibodies for therapy failure in patients with head and neck cancer.

High rate of p53 overexpression in head and neck carcinomas detected with a refined ELISA.

p53 mutations are amongst the most prevalent alterations in human cancer. Overexpression of p53 is usually caused by mutation and is observed in a high percentage of squamous cell carcinomas of the head and neck (SCCHN). Fifty two fresh samples of SCCHN were examined for p53 overexpression and 23 tumor-free tonsils served as controls. Using the monoclonal antibody Pab 1801 a refined ELISA technique was employed. In contrast to established ELISA procedures tumor tissue was pulverized at -80 degrees C prior to the actual ELISA (ELISA I). Comparative p53 detection was carried out by immunohistochemistry (IHC) and a commercially available ELISA kit (ELISA II). The modified ELISA I revealed p53 overexpression in 48 tumor samples (92%). p53 detection was obtained in 26 cases (50%) with ELISA II and with IHC 39 stained positive for p53 (75%). All of the controls were negative for p53 with ELISA and IHC. The p53 staining in IHC showed a significant correlation with the grading of the tumor. The ELISA results of the p53 overexpression did not show any correlation with tumor size or stage and rate of metastasis or other clinical parameters. This ELISA represents a more sensitive detection method of p53 than any other technique so far. It improves on former ELISA and IHC results on p53 overexpression in squamous cell carcinoma of the head and neck and underlines the involvement and the importance of the p53 tumor suppressor protein in carcinogenesis of head and neck cancer.