Angiogenesis and lymphangiogenesis in thyroid proliferative lesions: relationship to type and tumour behaviour.

The role of angiogenesis and lymphangiogenesis in thyroid cancer pathogenesis has not been elucidated. Patterns for tumour behaviour and metastasic spread vary according to tumour type and whether differences in the angiogenic or lymphangiogenic phenotype influence the route for tumour metastases or determine a more aggressive behaviour has not been fully explored. The angiogenic and lymphangiogenic phenotypes of a large cohort of thyroid proliferative lesions (n=191) were studied. Using immunohistochemistry for CD34, lymphatic vessel endothelial receptor-1 (LYVE-1) (specific markers for vascular and lymphatic endothelium respectively), vascular endothelial growth factor (VEGF-A), VEGF-C and fibroblast growth factor-2 (FGF-2), this study analyses microvascular density (MVD), lymphatic vascular density (LVD), and expression of angiogenic and lymphangiogenic factors in normal thyroid (NT; n=19), multinodular goitre (n=25), toxic multinodular goitre (n=8), Graves' hyperplasia (n=22), follicular adenoma (n=54), papillary carcinoma (PC; n=27), incidental papillary microcarcinoma (PMC; n=8), follicular carcinoma (FC; n=20) and medullary carcinoma (MC; n=8). MVD was decreased in proliferative lesions, benign and malignant, compared with NT (P<0.0001). In contrast, VEGF-A expression was increased in thyroid carcinomas (PC, FC and MC) when compared with PMC, benign lesions and NT (P<0.0001). LVD was higher in PC and PMC (P=0.001), and VEGF-C expression was increased in PC (P<0.0001). Despite higher LVD and increased expression of VEGF-A and VEGF-C in thyroid cancers, these markers were not related to poor prognosis in terms of tumour size, multifocality and/or presence of lymphatic or distant metastases. In conclusion, angiogenesis is reduced in thyroid proliferative lesions compared with NT tissue. However, VEGF-A expression is upregulated in thyroid cancers. Lymphangiogenesis and VEGF-C expression are increased in thyroid tumours prone to lymphatic metastases. This may be an important mechanism underlying the differences in metastatic behaviour between papillary and follicular thyroid cancer.

Angiogenesis in prolactinomas: regulation and relationship with tumour behaviour.

Tumours are dependent on angiogenesis for growth and inhibition of angiogenesis has become a target for antineoplastic therapy. In the pituitary, unlike other tissues, vascularization is lower in adenomas compared to the normal gland. Despite this finding, a relationship between increased vascularity and several aspects of prolactinoma behaviour such as size, invasiveness, surgical outcome and malignancy, has been demonstrated. The process of angiogenesis is the result of a balance of stimulating and inhibiting factors. It is likely that an interaction between gene expression (such as pituitary tumour transforming gene (PTTG) and a novel gene located within the Edpm5 quantitative trait locus), hormonal stimuli including oestrogens, dopamine, 16 kDa fragments of prolactin and proangiogenic and antiangiogenic growth factors (for example, vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF-2), determine the final angiogenic phenotype of prolactinomas, and thus subsequent tumour behaviour. The elucidation of all the factors involved in the regulation of angiogenesis and their interactions might open new possibilities in the treatment of prolactinomas, especially in those cases with resistance or intolerance to dopamine agonists.

Morphologic changes and molecular regulation of angiogenesis in pituitary adenomas.

Angiogenesis, the process of development of a new vasculature, plays a crucial role in tumour growth. In the pituitary, unlike other tissues, vascularization is lower in adenomas compared to the normal gland. Despite this finding, a relationship between increased vascularity and some aspects of tumour behaviour such as size, invasiveness, surgical outcome and malignancy, has been demonstrated. The process of angiogenesis is the result of a balance of stimulating and inhibiting factors. It is likely that an interaction between gene expression (such as pituitary tumour transforming gene), hormonal stimuli including oestrogens, corticosteroids, dopamine, 16-kDa fragments of prolactin and growth hormone, somatostatin analogues, and pro- and anti-angiogenic growth factors (e.g. vascular endothelial growth factor and fibroblast growth factor), determine the final angiogenic phenotype of pituitary tumours, and thus subsequent tumour behaviour.

Angiogenesis and lymphangiogenesis in parathyroid proliferative lesions.

Angiogenesis and lymphangiogenesis are involved in tumoral growth and metastatic spread. There is little information on angiogenesis and no available data on lymphangiogenesis in parathyroid glands (PTG). Using immunohistochemistry for CD34, LYVE-1 (specific markers for vascular and lymphatic endothelium, respectively), vascular endothelial growth factor (VEGF)-A, VEGF-C, and fibroblast growth factor (FGF)-2, this study analyzes microvascular density (MVD), lymphatic vascular density (LVD), and expression of angiogenic and lymphangiogenic growth factors in 13 normal PTG, 77 parathyroid adenomas (PTA), and 17 primary parathyroid hyperplasia (PPH). MVD was higher in PPH and PTA, compared with PTG (P < 0.001). There was no difference in VEGF-A expression among groups. In contrast, FGF-2 expression was higher in PPH, compared with PTA and PTG (P < 0.0001). FGF-2 scores and MVD were significantly correlated (r = 0.43). LVD did not differ among groups, and VEGF-C expression was unrelated to LVD. There was no relationship between MVD and tumor behavior (adenoma size, PTH, or calcium). In conclusion, this study shows increased angiogenesis in parathyroid proliferative lesions compared with normal glands and suggests that FGF-2 is proangiogenic in parathyroid tissue. In PTA, tumor behavior is not related to angiogenic phenotype. This is the first demonstration of lymphatic vessels in PTG, but the lack of correlation with VEGF-C expression suggests that VEGF-C is not the primary lymphangiogenic factor.

Parathyroid adenomas and cardiovascular risk.

In recent decades, primary hyperparathyroidism (pHPT) has changed its clinical presentation from a disease with bone and renal involvement to a frequently asymptomatic disorder detected on routine biochemistry. Nevertheless, it remains unclear whether patients with untreated mild asymptomatic hyperparathyroidism are at risk for other complications such as increased morbidity and mortality from cardiovascular diseases. There are limited data on the incidence of cardiovascular abnormalities in mild pHPT. However, pHPT has been associated with increased risk of death from cardiovascular disease, hypertension, left ventricular hypertrophy (LVH), valvular and myocardial calcifications, impaired vascular reactivity, alterations in cardiac conduction, impaired glucose metabolism, dyslipidaemia, and alterations in body composition. The nature of some of these associations is in question, because cure of pHPT does not lead to improvement of the cardiovascular disorder e.g. hypertension. In contrast, currently available data suggest that LVH, impaired glucose metabolism and dyslipidaemia may improve after surgery and that successful parathyroidectomy could decrease the excess mortality in patients with pHPT due to cardiovascular disease.

Antiangiogenic effects of somatostatin analogues.

Inhibition of angiogenesis has become a target for antineoplastic therapy and for treatment of retinal neovascularization. The presence of somatostatin receptors on tumour cells and on the proliferating vascular endothelium has led to several in vitro and in vivo studies to investigate the antiproliferative and antiangiogenic effects of somatostatin analogues. Currently available data suggest that somatostatin analogues might inhibit angiogenesis directly through somatostatin receptors present on endothelial cells and also indirectly through the inhibition of growth factor secretion such as IGF-I and vascular endothelial growth factor (VEGF) and reducing monocyte chemotaxis. However, beneficial effects on inhibition of neovascularization have been questioned by some studies. More work is therefore required to firmly establish the role of somatostatin analogues as potential antiangiogenic therapy. The currently available somatostatin analogues have high affinity for somatostatin receptor subtype 2 (sst2) and, to a lesser extent, sst5 and sst3. However, because vascular endothelial cells express several types of somatostatin receptors, it will be important to investigate somatostatin analogues with different receptor subtype affinities, which might increase the spectrum of available therapy for tumours.

Comparison of peripheral arterial reconstruction in diabetic and non-diabetic patients: a prospective clinic-based study.

UNLABELLED: To assess the efficacy and safety of lower extremity arterial reconstruction in diabetic and non-diabetic subjects during a 3-year period. A prospective clinic-based study between 1994-1999 in Area 7, Madrid, with a population of 569307 and an estimated diabetic population of 37932 (15505 men and 22427 women). The level of arterial reconstruction and associated risk factors were ascertained. RESULTS: A total of 588 peripheral revascularization surgical procedures were performed in 481 patients. The diabetic patients (n=174, 36.2%) underwent 222 surgical procedures (including 48 follow-on operations, 21.6%), and 307 non-diabetic subjects underwent 366 surgical procedures (59 follow-on operations, 16.1%). The numbers of surgical procedures per 100000 people at risk and year were 18.8 and 1.8 for non-diabetic men and women, respectively, and 145.1 and 29.0 for men and women with diabetes mellitus (7.7- and 16.2-fold, respectively). Age at reconstruction surgery was 2 and 5 years earlier in non-diabetic than in diabetic men and women, respectively. Diabetic patients had a higher neuropathy score (P<0.05) and were less frequently smokers (P<0.05) than non-diabetic subjects. Diabetic subjects more frequently had distal reconstruction while proximal arterial reconstruction was more often performed in non-diabetic subjects. Between 64.6 and 80.4% of people with diabetes and 82.3 and 88.9% of non-diabetic subjects had no complications during their in-hospital stay. Distal amputation simultaneous to arterial reconstruction was the most frequent morbidity of people with diabetes during the study (P<0.05). Despite a graft occlusion rate after femoropopliteal revascularization significantly higher than in non-diabetic people (P<0.05), diabetic people more often required lower extremity amputations (LEAs) for the same level of bypass (P<0.01). Cumulative limb salvage rates were lower in diabetic patients than in non-diabetic subjects at femoropopliteal (49.2 vs. 89.7%; P<0.001), femorodistal (73.5 vs. 95.2%; P<0.01), and distal reverse (77.9 vs. 87.3%; P<0.05) arterial reconstruction, at the end of the third year, but similar after aorto-iliac reconstruction (93.1 vs. 97.5%). A higher neuropathy score and the presence of foot ulcers were associated to significantly lower limb salvage in diabetic patients (P<0.05), but not in non-diabetic people. Survival rates after 3 years were similar between diabetic and non-diabetic populations after aorto-iliac (93.1 vs. 97.5%), femoropopliteal (97.2 vs. 90.3%), and distal reverse (93.2 vs. 98.1%) revascularization, and slightly lower in diabetic compared to non-diabetic patients after femorodistal revascularization (82.1 vs. 96.3%; P<0.05). CONCLUSION: Although limb salvage after arterial reconstruction is lower in diabetic than in non-diabetic subjects, particularly in those with a higher neuropathy score, this surgical approach can be applied in both diabetic and non-diabetic subjects with otherwise similar outcome.

Influence of stress on calcification of delipidated bovine pericardial tissue employed in construction of cardiac valves.

Since the development of cardiac bioprostheses, numerous chemical treatments have been assayed to prevent mineralization. The effectiveness of chemical treatments that eliminate lipids from the tissue was tested by combining two models. First, handmade bovine pericardial bioprostheses, subjected to chemical treatment with chloroform/ methanol and glutaraldehyde or treated with glutaraldehyde alone for use as controls, were subjected to mechanical stress in a heart valve, accelerated wear tester (100 x 10(6) consecutive cycles). Then, the bioprostheses were unstitched and tissue samples were taken from the portion subjected to maximal stress (P1) and from that surrounding the sewing ring, which had not been subjected to mechanical stress (P2), for subcutaneous implantation. After 21 and 60 days of implantation, we observed calcification of the samples subjected to mechanical stress, even after delipidating treatment, with no significant differences with respect to the control group. However, the treated samples from the portion not subjected to mechanical stress presented a slighter accumulation of calcium after 60-day implantation (5.60 +/- 3.09 mg Ca2 +/g dry weight of tissue) versus the control group (47.17 +/- 20.4 mg Ca2+/g dry weight of tissue), the difference of which was statistically significant (p < 0.01). At the time of these medium-term studies, marked calcification was observed in tissue subjected to delipidating treatment in the zones that underwent mechanical stress.

Inhibition of the calcification of porcine valve tissue by selective lipid removal.

Since the development of cardiac prostheses, numerous chemical treatments have been assayed to prevent the process of their mineralization, causing 60% of the failures. The effect of the extraction of lipids from the tissue employed in porcine valves is assessed in a model of subcutaneous implantation in rats. Tissue from aortic and pulmonary porcine valves was treated with chloroform-methanol and 0.625% glutaraldehyde and was implanted into young rats for periods of 21 and 60 d. The calcium accumulated was then quantified by atomic absorption. The effectiveness of this treatment is demonstrated by the detection of much lower calcium values than in the control group. For aortic valve tissue, the values obtained were 40.5 and 188.1 micrograms Ca2+/mg dry weight of tissue for implantation times of 21 and 60 d, respectively, versus 5.48 and 1.4 micrograms Ca2+/mg dry weight of tissue for the same tissue treated with chloroform-methanol. The values obtained with pulmonary valve tissue were very similar: 72.46 and 108.06 micrograms Ca2+/mg dry weight tissue versus 0.67 and 0.80 micrograms Ca2+/mg dry weight tissue for implantation periods of 21 and 60 d, respectively. Thus, phospholipids may be totally or partially responsible for the calcification of the porcine valve tissue employed in the construction of cardiac bioprostheses.

Wide distribution of two subtypes of HIV-1 in Thailand.

PIP: Scientists wanted to identify the genetic characteristics of 2 HIV-1 subtypes in Thailand. Staff from regional laboratories of the Ministry of Public Health took blood samples from people in various high risk groups and from all regions of the country. Staff at the National Institutes of Health in Bangkok then did lymphocyte separation, DNA extraction, and virus culture. They took the extracted DNA specimens and sent them to the US Centers for Disease Control where scientists did serologic testing, polymerase chain reaction, and sequence determination. They used Kimura's method to study sequence variations. They sequenced 300 nucleotides, including the C2-V3 domains of HIV-1 envelope gene and/or hybridization. Every risk group had HIV-1 subtype A, but subtype B was mostly found in drug users. Subtype A had spread mainly among heterosexuals. The mean intraperson variation for subtypes A and B stood at 2% and 2.7%, respectively, while the interperson variation within subtype A and B stood at 3.8% and 3.7%, respectively. The mean interperson variation between subtypes A and B from different persons was 18.1%. Phylogenetic tree analysis showed that subtype B identified with about 85% of the sequence as that of the North American isolates, making it more closely related to them than to African isolates (about 75% sequence identity). On the other hand, subtype A had a GPGQ motif at the V3 crown which was common among African HIV-1 isolates. Antibodies which usually recognize HIV-1 MN strains (which have the GPGR motif) may not react wholly with the V3 loop from the Thailand subtype A viruses, thus the GPGQ motif at the V3 crown may pose a problem. Now for the first time, scientists can follow the natural history of 2 HIV-1 subtypes and determine their relative pathogenicity and transmission efficiency between adults or from mother to infant. The relative homogeneity of the HIV-1 strains in Thailand presents a theoretical advantage in designing vaccines for potential large-scale clinical trials.^ieng

Parámetros funcionales espirométricos en adultos - jóvenes no fumadores en Quito

Los parámetros funcionales obtenidos por espirometria son indicadores sensibles de la integridad funcional ventilatoria, y factores fisiológicos como el peso, talla, sexo, raza y altitud geográfica; son determinantes para su correcta interpretación. En éste estudio se analiza la capacidad vital forzada (CVF), el volumen generado al 1 seg de la espiración forzada (FE V1), el generado al 50//de la CVF (FEV 50), el flujo espiratorio máximo medio(MMEF), y el cociente FEV1/CVF; por medio de espirómetria automatizado. Se incluyen 34 hombres (H) y 31 mujeres (M) adultos jóvenes (20+-2 H vs 20+-2M,años), con nomopeso (IMC: 21 +- 2 H vs 22 +- 2 M); aparentemente sanos, no fumadores activos ni exfumadores y residentes a 2820 m/snm (Quito). Los valores teóricos y los observadores corregidos por edad, sexo, talla) fueron siempre estadisticamente superiores en H que en M. Los valores observados alcanzaron o superaron el 100 por ciento de los teóricos, sin diferencia entre sexos; excepto para el MMEF que fue superior H(142 +- 65 vs 115 +- 31 por ciento, p=0.04). El cociente FEV1/cvf demostró integridad ventilatoria en H y M: 93+-9 vs 94+-9por ciento(ns). Comparando con una población de sujetos similar a 150 m/snm (Austria), se observó que la CVF y el FEV1/CVF es superior en los sujetos analizados en Quito. Con los valores de refernecia internacional, tan sólo la CVF en M fue inferior. La población analizada, demuestra integridad funcional ventilatoria (FEV1/CVF 80//), corroborandose diferencias según el sexo y variaciones de adaptación crónica a la altitud (2820m/snm).Además, de forma preliminar se reportan valores de referencia local de parámetros espirométricos, en adultos jóvenes con normopeso y no fumadores.

[Working women and health of 4 groups of women in Guadalajara, Mexico]. / El trabajo femenino y la salud de cuatro grupos de mujeres en Guadalajara, México.

Today, the incorporation of women into the work force has changed the profile of health concerns of this population, extending it beyond the traditional gynecological/obstetrical framework. In order to describe the health problems of women in the context of their activities both inside and outside the home, a descriptive study was carried out using a four-part questionnaire (sociodemographic characteristics, domestic activities, renumerated activities, and the Cornell Medical Index) to identify similarities and differences among nurses, teachers, secretaries, and housewives living in Guadalajara, Mexico, in 1989. The results showed that the working woman's schedule, defined as the time devoted to work both inside and outside the home, is very long in all the groups studied, amounting to a total of between 66 and 78 hours a week. The housewives spend an average of 70 hours a week on domestic tasks, while the nurses, teachers, and secretaries spend between 34 and 42 hours a week on such activities. With regard to work-related risks, occupational diseases were the most common complaint of all the groups, especially the teachers. On the other hand, housewives had the highest overall morbidity according to the Cornell Medical Index. These observations point out that different occupational health risks and morbidity indexes are associated with different activities performed by women, and it is suggested that these differences should be examined more fully through descriptive studies on women's health such as the one presented here.

[The geographical distribution of women's health problems in Jalisco, Mexico]. / Distribución espacial de la problemática de salud de la mujer en Jalisco, México.

The epidemiological studies on women's health, with relation to their geographical distribution (rural and urban), have focused on the areas of fertility and family planning. This work attempts to open up, to a worldwide level of comprehension, the perspectives of the problems related to women's health. It show the results of an investigation of two population groups of women, one in the rural zone, and the other in the urban zone; both groups were from the state of Jalisco, Mexico. The objectives were: to identify the more frequent health problems occurring in women and to establish the similarities and differences between these two female groups. The information was obtained by means of unique interviews using questionnaires. Sociodemographic variables, housing, and sanitation were studied, as well as a health questionnaire which was divided into apparatus and systems. Better sanitary conditions and more favorable sociodemographic indicators were found among women in the urban zone as opposed to those in the rural zone. The most frequent health problems are, in decreasing order, those located in the nervous, digestive, cardiovascular, and genital-urinary systems. There exists a direct relationship between the frequency of health problems and age. Generally, the women most affected are those in the rural zone. It is difficult to establish comparisons with the health conditions of women in other areas due to lack of research that makes differentiations with regard to sex (in this case, those focusing on women). We consider it of interest to continue with insightful investigations of chronic, degenerative, and deficiency problems, as well as those related to self-attention.

[Correlation of the transaortic gradient determined with doppler echocardiography versus catheterization in patients with aortic stenosis]. / Correlación del gradiente transaórtico determinado por eco-Doppler vs. cateterismo en pacientes con estenosis aórtica.

The purpose of this report is to evaluate the reliability of a non-invasive estimation of a transaortic gradient in patients with valvular aortic stenosis by doppler echocardiography. We compared the transvalvular gradients obtained by cardiac catheterization (invasive) versus the estimation by non-invasive technique such as continuous-wave doppler in 30 consecutive patients with valvular aortic stenosis. When compared the peak velocity (Vmax) of the aortic jet versus the gradient obtained by cardiac catheterization we found a correlation coefficient (r) of 0.83 and when compared the gradient obtained by both methods we found an r value of 0.85. These results show that the calculations of aortic gradient by echo-doppler, are reliable. Besides this method allowed us to establish the correct diagnosis and to follow up these patients.

Purity, antigenicity and immunogenicity of the hepatitis B surface antigen purified by five different methods.

Five published methods for the purification of HBsAg from plasma were compared for specific activity (SA), degree of purification, and yield. The SA value was determined by dividing the reciprocal of the end point dilution per milliliter as determined using a commercial radioimmunoassay (AUSRIA II; Abbott Laboratories, North Chicago, IL) by the protein concentration quantitated by the Lowry method. HBsAg purified by two consecutive isopycnic ultracentrifugation separations in KBr and one rate-zonal separation in sucrose using a zonal rotor (Ti-14, Beckman, Palo Alto, CA) yielded a preparation which gave the highest SA value, degree of purification and yield as compared to four other methods. Each purified preparation was adsorbed to alum adjuvant and injected into mice to determine the immunogenic dose at which 50% of the animals elicited an anti-HBs response (ID50). The zonal rotor method resulted in the lowest ID50 value (365 ng/ml) supporting the highest SA value. Furthermore, SDS polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis revealed that this preparation had the greatest number of HBsAg-specific polypeptides (N = 7) and the fewest contaminating polypeptides (N = 5). The contaminating proteins were identified as alpha-2-macroglobulin, heavy chains of IgG and IgM, immunoglobulin kappa chain, and albumin.