Thymosin ß4 and ß10 are highly expressed at the deep infiltrative margins of colorectal cancer - A mass spectrometry analysis.

OBJECTIVE: Colorectal cancer (CRC) is a complicated tumor, involving several oncogenic signaling pathways, and with a molecular mechanism not fully understood yet. The implication of thymosin ß4 (Tß4) with tumor insurgence and in migration of CRC cells was evidenced in the past with different methodologies, while Tß10 connection with CRC has been sporadically investigated. This study focused on the implication of both types of thymosin in CRC progression and invasion by analyzing the changes in their levels according to different zones of the tumor, and to Dukes stage and budding index. PATIENTS AND METHODS: Tß4 and Tß10 were analyzed in deep and superficial tumor samples, and normal mucosa from 18 patients. Concentrations of Tß4 and Tß10 have been measured by high-pressure liquid chromatography (HPLC) coupled to electrospray-ion trap mass spectrometry (ESI-IT-MS). MS data were compared by t-test and ANOVA statistical analysis. Identification of thymosin and their proteoforms has been performed by HPLC-high resolution-ESI-IT-MSMS. RESULTS: Both Tß4 and Tß10, exhibited intra-tumoral quantitative differences, being upregulated in the deep part of the CRC. They exhibited, moreover, strong association with the Dukes stage and the budding grade, being more concentrated in patients at Dukes stage B and with budding index "2". CONCLUSIONS: The results obtained in the present investigation encouraged the hypothesis that the two thymosin are involved in colorectal cancer progression, and in promoting cancer invasion. Thus, they are good candidates to be diagnostic/prognostic biomarkers and therapy targets.

Stability of cachet phakic intraocular lens position during 6-months follow-up.

PURPOSE: To evaluate the position stability of a phakic intraocular lens (Cachet pIOL; Alcon, Laboratories, Inc., Fort Worth, TX) in the anterior chamber (AC) during a 6-months follow-up. METHODS: Thirty eyes of 16 subjects underwent a Cachet pIOL implantation for the correction of high myopia from -6.50 to -16.00 D with plano targeted refraction. The position stability of the Cachet pIOL was evaluated using an Anterior Segment-OCT (AS-OCT, Carl Zeiss AG, Oberkochen, Germany) at 1- and 6-months postoperatively. Three measurements have been taken into account: 1) the minimum distance between the anterior surface of the Cachet pIOL optic disk and the central corneal endothelium; 2) the minimum distance between the optic disk's edges of the pIOL and the endothelium; 3) the minimum distance between the posterior surface of the pIOL optic disk and the anterior surface of the crystalline lens. The endothelial cell density (ECD) was also recorded. RESULTS: No statistically significant changes of the Cachet pIOL position in the AC were found during follow-up. The average changes were ≤0.1 mm between 1- and 6-months postoperatively (P>0.05). At the end of follow-up, The mean ECD loss was 0.7 % (from 2794 ± 337 cell/mm(2) to 2776 ± 388 cell/mm(2); P>0.05). CONCLUSION: A high position stability of the Cachet pIOL in the anterior chamber was shown during a 6-months follow-up.

Retinal sensitivity to flicker modulation: reduced by early age-related maculopathy.

PURPOSE: To evaluate retinal, cone-mediated flicker sensitivity (CFS) in age-related maculopathy (ARM) by quantifying response gain and threshold of the focal electroretinogram (FERG) to flicker modulation. METHODS: Nineteen patients with ARM (visual acuity > or =20/30) and 11 age-matched control subjects were examined. Twelve patients had less than 20 soft drusen in the macular region and no hyper-/hypopigmentation (early lesion), whereas seven had more than 20 soft drusen and/or focal hyper-/hypopigmentation (advanced lesion). Macular (18 degree ) FERGs were elicited by a sinusoidally flickering (41 Hz) uniform field (on a light-adapting background) whose modulation depth was varied between 16.5% and 94%. Amplitude and phase of the response's fundamental harmonic were measured. RESULTS: In both control subjects and patients with ARM, log FERG amplitude increased with log stimulus modulation depth with a straight line (power law) relation. However, the slope (or gain) of the function was, on average, steeper in control subjects than in patients with either early or advanced lesions. Mean FERG threshold, estimated from the value of the log modulation depth that yielded a criterion response, did not differ between control subjects and patients with early lesions but was increased (0.35 log units) compared with control subjects in those with advanced lesions. In both patient groups, but not in control subjects, mean FERG phase tended to delay with decreasing stimulus modulation depth. CONCLUSIONS: Retinal CFS losses can be detected in ARM by evaluating the FERG as a function of flicker modulation depth. Reduced response gain and phase delays, with normal thresholds, are associated with early lesions. Increased response thresholds, in addition to gain and phase abnormalities, may reflect more advanced lesions. Evaluating CFS by FERG may directly document different stages of macular dysfunction in ARM.

Focal electroretinograms and fundus appearance in nonexudative age-related macular degeneration. Quantitative relationship between retinal morphology and function.

BACKGROUND: The aim of this study was to evaluate the focal electroretinogram (FERG), an objective indicator of outer retinal function, in nonexudative age-related macular degeneration (NE-AMD), and to compare FERG results with morphological lesions assessed by stereoscopic fundus photographs and fluorescein angiograms. METHODS: Twenty-five patients (25 eyes) with bilateral NE-AMD (visual acuity of the study eyes > or = 0.4) as well as 10 age- and sex-matched control subjects (10 eyes) were evaluated. FERGs were recorded from the macular region (9 degrees) in response to sinusoidal stimuli flickered at 32 Hz. Amplitude and phase angle of the Fourier-analyzed FERG fundamental component were measured. Fundus lesions were graded from color slides according to the Wisconsin age-related maculopathy grading system . Fluorescein angiograms were evaluated by an image analysis technique to compute the area with pathological hyperfluorescence (associated with drusen and/or retinal pigment epithelial atrophy) within the macular (approximately 9 degrees x 9 degrees) region. RESULTS: Compared to control eyes, NE-AMD eyes had a reduction in the mean FERG amplitude (57% loss, P<0.001) with no phase changes. Amplitudes of individual affected eyes were negatively correlated with either the Wisconsin grading score (r = -0.63, P < 0.001) or the percentage area of pathological hyperfluorescence (r = -0.70, P<0.01). Eyes with minimal NE-AMD lesions (Wisconsin score < or = 6) and normal acuity had a lower mean amplitude (47% loss, P < 0.05) than that of control eyes. CONCLUSIONS: The results indicate that, in NE-AMD, the FERG is altered in parallel with the extent and severity of fundus lesions. However, a functional impairment of outer macular layers, which is detected by FERG losses, could precede morphological changes typical of more advanced disease.

[A survey of demand for medical care in three public health clinics in Rio de Janeiro, Brazil]. / Demanda ambulatorial em três serviços da rede pública do município do Rio de Janeiro, Brasil.

A sample survey was conducted in three public ambulatory medical care units in Rio de Janeiro in order to show the demographic and nosological aspects of the clientele as well as to evaluate the quality of clinic records. The sample included 2,029 patients registered in the health clinics and 3,980 consultants from October 1, 1990 to September 30, 1991. The diagnoses were coded according to the 9th revision of the International Classification of Dieases. Females accounted for about 60% of the sample, and more than a half were between 15 and 49 years of age. Children under 10 years old made up 28% of the total. About 38% of the patients came from the poor areas of the city: the "favelas". The case files were poorly filled out, frequently lacking useful information. The most frequent cause was classified in the XVIo chapter of the ICD - ill-defined causes, followed by respiratory, infectious, genitourinary and circulatory diseases. External causes predominated in one of the health clinics, which is an emergency service. There was a great demand for preventive measures, such as prenatal care and child care, even at the clinic that was traditionally devoted only to curative medicine. The most frequent specific diagnoses were upper respiratory tract infection, hypertension, gynecological problems, prenatal care, and skin diseases. There were no records for referrals to other health services. The poor quality of the medical records causes problems in terms of quality of health care. Use of such record-keeping systems, even while criticizing them, is essential to improve them.