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Long-term vasectomy: effects on the occurrence and extent of atherosclerosis in rhesus monkeys.

We demonstrated previously that atherosclerosis develops more extensively in vasectomized cynomolgus macaques fed an atherogenic diet and speculated that the immunologic response to sperm antigens may have exacerbated the atherosclerosis. We report here that rhesus monkeys vasectomized for 9-14 yr and fed monkey chow (devoid of cholesterol and low in fat) rather than an atherogenic diet also had more extensive and severe atherosclerosis than did control animals of the same age. The extent of atherosclerosis was considered as the percentage of intimal surface with plaques. No control animals were found to have plaques in the thoracic aorta, but 7 of 10 vasectomized monkeys were affected. The plaques in the vasectomized monkeys occupied about 13% of the intimal surface. In 4 of 7 control monkeys and 7 of 10 vasectomized monkeys there were lesions in the abdominal aortas; the lesions were considerably more extensive and severe in the vasectomized animals. Lesions were also more common in iliac arteries of vasectomized animals, and the extent was increased about threefold. Plaques were seen at the carotid bifurcation in all of the animals of both the control and vasectomized groups. The carotid bifurcation plaques of the vasectomized monkeys were larger than those of the control animals on the right but not on the left side. Histologically, the lesions of vasectomized monkeys did not appear to be qualitatively different from those of control animals, even though they were larger and contained more collagen, lipid, and mucopolysaccharides. Grossly, the distribution of the lesions in the vasectomized animals was different from that in the control animals, and that of lesions induced by atherogenic diets, i.e., the lesions were distributed randomly within the artery rather than around bifurcations. More extensive atherosclerosis was noted among vasectomized animals that were found to lack demonstrable circulating free antisperm antibodies. On the basis of the observations made in this study, we suggest that the antisperm antibodies that form after vasectomy may result in circulating immune complexes that exacerbate atherosclerosis.

Animals↗

Adaptations of the vestibular system to short and long-term exposures to altered gravity.

Long-term space flight creates unique environmental conditions to which the vestibular system must adapt for optimal survival of a given organism. The development and maintenance of vestibular connections are controlled by environmental gravitational stimulation as well as genetically controlled molecular interactions. This paper describes the effects of hypergravity on axonal growth and dendritic morphology, respectively. Two aspects of this vestibular adaptation are examined: (1) How does long-term exposure to hypergravity affect the development of vestibular axons? (2) How does short-term exposure to extremely rapid changes in gravity, such as those that occur during shuttle launch and landing, affect dendrites of the vestibulocerebellar system? To study the effects of longterm exposures to altered gravity, embryonic rats that developed in hypergravity were compared to microgravity-exposed and control rats. Examination of the vestibular projections from epithelia devoted to linear and angular acceleration revealed that the terminal fields segregate differently in rat embryos that gestated in each of the gravitational environments.To study the effects of short-term exposures to altered gravity, mice were exposed briefly to strong vestibular stimuli and the vestibulocerebellum was examined for any resulting morphological changes. My data show that these stimuli cause intense vestibular excitation of cerebellar Purkinje cells, which induce up-regulation of clathrin-mediated endocytosis and other morphological changes that are comparable to those seen in long-term depression. This system provides a basis for studying how the vestibular environment can modify cerebellar function, allowing animals to adapt to new environments.

Adaptation, Physiological↗

Maternal smoking during pregnancy affects children's vigilance performance.

Aspects of attentional behaviour in 4--7-year-olds, as assessed by auditory and visual vigilance tasks, were related to prenatal exposure to cigarettes. Data on 76--79 children born to healthy, white, predominantly middle-class women were analyzed using multiple regression techniques controlling for potentially confounding variables including postnatal second hand smoke exposure. Cigarette smoking during pregnancy was related to an increased activity level of the children during the tasks and increased errors of commission in the auditory task and, to a lesser degree, in the visual task. After controlling for confounding factors, the relationship between prenatal smoking and errors of omission did not retain significance. The combination of results suggest that the deficits in attention may reflect impulsive responding and increased overall activity.

Arousal↗

Maternal smoking during pregnancy and risk of childhood cancer.

In a case-control study of childhood cancer a dose-response relationship was found between the number of cigarettes smoked per day by the mother during pregnancy and cancer risk in the offspring. When all tumour sites were considered the cancer risk was 50% higher for the most exposed group than for the controls. The risk was doubled for non-Hodgkin lymphoma, acute lymphoblastic leukaemia, and Wilms' tumour. These findings provide further evidence for the harmful effects of cigarette smoke on the growing fetus.

Adolescent↗

Laparoscopic radical nephrectomy: long-term outcomes.

BACKGROUND: Although more than a decade of experience with laparoscopic radical nephrectomy indicates it is an alternative to open surgery for localized renal-cell carcinoma (RCC), the long-term oncologic effectiveness of this procedure remains to be established. MATERIALS AND METHODS: A thorough MEDLINE and PubMed literature research on long-term outcomes of laparoscopic radical nephrectomy was performed, and all pertinent articles were reviewed in detail. This review was formulated on the current cancer indication, the oncologic basis, the oncologic efficacy, and the longterm oncologic effectiveness of the procedure, including laparoscopic cytoreductive nephrectomy, with regard to metastasis, port-site tumor recurrence, and the relation to laparoscopic partial nephrectomy. Furthermore, the authors' previous report on the intermediate-term efficacy of laparoscopic radical nephrectomy was updated. RESULTS: With increasing experience, the indications for laparoscopic radical nephrectomy continue to expand. There were many reports of intermediate-term, two reports of long-term, and our up-to-date outcomes analyzing the management of localized RCC that showed effective cancer control with no statistically significant difference between laparoscopic and open radical nephrectomy in the true 5- and 10-year survival analysis. CONCLUSION: Long-term data, critical in the evaluation of any treatment for cancer, are currently available with respect to laparoscopic radical nephrectomy for localized RCC.

Adult↗

Effects of desogestrel on carbohydrate metabolism.

Associated with progesterone and the synthetic progestins used in oral contraceptives is a dose-dependent impairment of carbohydrate metabolism. It is well known that in the general population hyperinsulinemia and alterations in glucose metabolism are significant risk factors for the development of cardiovascular disease. Studies that use curve analysis of glucose tolerance tests have demonstrated insulin resistance, rises in plasma insulin, and relative glucose intolerance in women using oral contraceptives. Desogestrel, a new progestin, has been demonstrated to have generally less pronounced effects on these parameters of carbohydrate metabolism.

Animals↗

Breastfeeding by HIV-1-infected women and outcome in their infants: a cohort study from Durban, South Africa.

BACKGROUND: Women in developing countries have the difficult choice of balancing the risk of transmitting HIV through breast milk against the substantial benefits of breastfeeding. It is not known, however, whether the benefits of breastfeeding are the same when the mother is HIV-infected. Therefore, we examined the impact of breastfeeding on infections, growth and mortality in the infants of HIV-1-infected women. METHODS: Infants of HIV-1-positive women were followed from birth and at each visit they were examined, growth parameters were recorded and notes were made of feeding method, and of current and interim illnesses. RESULTS: Of the 43 HIV-infected and 90 non-infected infants for whom feeding data were available, 36 infants (27%) were exclusively breastfed, 76 (57%) received mixed feeding, and 21 (16%) received formula only. The HIV transmission rate was 39% in those exclusively breastfed, 24% in those fed exclusively on formula and 32% in those receiving mixed feeding [relative risk (RR), 7.39; 95% confidence interval (CI), 1.67-32.6 between the exclusive breast and formula only groups]. There was a stepwise increase in the transmission rate with duration of exclusive breastfeeding of 1, 2 and 3 months (45%, 64%, and 75%, respectively). Of the infected infants, seven (50%) exclusively breastfed, 13 (51%) of those on mixed feeds and none on formula only developed AIDS; exclusively breastfed infants had a slower rate of progression to AIDS (mean age, 7.5 months versus 5.0 months, P = 0.2242) than those on mixed feeds. Mortality (which occurred in the infected infants only) was 19% in the exclusively breastfed infants; 13% in those on mixed feeds and 0% in those exclusively formula-fed. The frequency of failure to thrive and episodes of diarrhoea and pneumonia were not significantly different between the three groups in both the infected and non-infected infants. CONCLUSIONS: Exclusive breastfeeding by HIV-infected women does not appear to protect their infants against common childhood illnesses and failure to thrive, nor does it significantly delay progression to AIDS. The implication of the trend towards differential mortality rates according to feeding groups is uncertain and requires further investigation.

Breast Feeding↗

Inappropriate use of daily mortality analyses to estimate longer-term mortality effects of air pollution.

BACKGROUND: To avoid the usual problems of multi-population correlation studies of air pollution and mortality, and for reasons of convenience, daily time-series mortality studies within single populations have recently become popular in air pollution epidemiology. Such studies describe how the short-term distribution of deaths relates to short-term fluctuations in air pollution levels. The regression-based risk coefficients from these acute-effects studies have been widely used to estimate the excess annual mortality within a population with a specified average level of air pollution. Such calculations are inappropriate. Since daily time-series data provide no simple direct information about the degree of life-shortening associated with the excess daily deaths (many of which are thought to be due to exacerbation of well-advanced disease, especially cardiovascular disease), such data cannot contribute to the estimation of the effects of air pollution upon chronic disease incidence and long-term death rates. Yet it is that category of effect that is of most public health importance. CONCLUSION: Such effects are best estimated from long-term cohort studies that incorporate good knowledge of local (or personal) exposure to air pollutants and of potential confounders. Time-series studies, properly evaluated, can identify the existence of acute toxic effects of transient peak levels of air pollution; they are thus useful for monitoring acute toxicity and for identifying the most noxious pollutants. However, to quantify the long-term health impacts of air pollution we cannot use acute-effects data.

Air Pollution↗

International migration: demographic and socioeconomic consequences in the United Kingdom and Europe.

"This article evaluates the consequences of international migration since World War II, with particular reference to Great Britain. It emphasizes the substantial differences between the origins and responses to immigration in the United Kingdom and that of the rest of Western Europe." It is found that "people of non-European origin from Commonwealth countries have predominated in postwar immigration to the United Kingdom. That migration neutralized the previously dominant pattern of emigration and increased U.K. population by about 3 million people through immigration and higher fertility, with only slight effects upon the age distribution."

Age Distribution↗

DNA vaccines employing intracellular targeting strategies and a strategy to prolong dendritic cell life generate a higher number of CD8+ memory T cells and better long-term antitumor effects compared with a DNA prime-vaccinia boost regimen.

We have previously shown that intradermal coadministration of DNA encoding Bcl-x(L), an antiapoptotic protein, with DNA encoding E7 antigen linked to the sorting signal of the lysosome-associated membrane protein type 1 (Sig/E7/LAMP-1) prolongs dendritic cell life and enhances antigen presentation through the MHC class I and II pathways. In the current study, we compared this approach with a conventional DNA prime-vaccinia boost protocol on the basis of their ability to generate antigen-specific CD8(+) memory T cells and longterm antitumor effects against an E7-expressing tumor. Mice primed and boosted with Sig/E7/LAMP-1 DNA mixed with Bcl-x(L) DNA generated significantly higher numbers of E7-specific CD8(+) memory T cells and a better long-term protective antitumor effect compared with mice primed with Sig/E7/LAMP-1 DNA and boosted with Sig/E7/LAMP-1 vaccinia (Vac-Sig/E7/LAMP-1). Furthermore, coadministration of Sig/E7 /LAMP-1 DNA mixed with Bcl-x(L) DNA also generated higher avidity E7-specific CD8(+) T cells than did vaccination with Sig/E7/LAMP-1 DNA followed by a Vac-Sig/E7/LAMP-1 booster. Our results indicate that coadministration of a DNA vaccine employing intracellular targeting strategies and a DNA encoding antiapoptotic proteins may potentially generate a higher number of memory CD8(+) T cells and better long-term protective antitumor effects compared with the conventional DNA prime-vaccinia boost regimen.

Animals↗

Long-term use of an injectable contraceptive: effect of depot-norethisterone oenanthate on carbohydrate metabolism.

In order to determine the metabolic effects of long-term use of the injectable contraceptive norethisterone oenanthate, plasma glucose and serum insulin concentrations were studied in two groups of women who had used the method continuously for at least five years. Group 1 comprised 24 subjects, from whom only fasting blood samples were taken. Despite similar plasma glucose concentrations to those of the controls, the subjects had significantly increased serum insulin concentrations (164.5 (39.9) v 120.3 (34.3) pmol/l, p less than 0.01). In addition the insulin:glucose ratios were also significantly increased (34.3 (8.5) v 24.6 (6.7), p less than 0.01), consistent with decreased insulin sensitivity. Group 2 comprised 13 of the original 24 subjects who also had an oral glucose tolerance test. Basal plasma glucose concentrations were similar in the subjects and their controls, whilst the significantly increased insulin:glucose ratios (35.0 (7.7) v 28.7 (5.6), p less than 0.05) were consistent with the results of the larger group. Following oral glucose challenge, plasma glucose concentrations, serum insulin concentrations and insulin:glucose ratios were similar in the subjects and their controls throughout the test. Thus, long-term use of norethisterone oenanthate injections is associated with a decrease in peripheral insulin sensitivity. However, these changes are not associated with any evidence of oral glucose intolerance.

Adult↗

Effects of the 1918 influenza pandemic mortality experience on subsequent fertility of the native population of Guam.

An analysis of the effects of the influenza epidemic that occurred in Guam in 1918 is presented. "A sample of records for 321 individuals who died during this peak epidemic period and for whom complete linked family records have been compiled was analyzed to study the effects of this mortality on subsequent fertility and population growth patterns." The results suggest that the long-term demographic effect of the epidemic on the native population was minimal.

Cause of Death↗

Incidence of pre-eclampsia in first full-term pregnancies preceded by abortion.

The incidence of preeclampsia in 1st term pregnancies was studied in relation to whether or not they were preceded by pregnancies which ended in abortion--spontaneous or induced. 220 patients with previous abortion were studied along with 2 sets of controls, 1 with no previous abortion or pregnancy and 1 with a 2nd term pregnancy. The incidence of preeclampsia was significantly lower than there had been a previous induced abortion but this was not as low as in cases with a 2nd term pregnancy. This finding may be interpreted as supporting the idea that pregnancy exerts a protective effect against the risk of preeclampsia which may have an immunological basis. A mechanism is suggested to explain the apparent "protective" effect of 1st pregnancies.

Abortion, Induced↗