Recurrent DNA copy number alterations in intestinal-type sinonasal adenocarcinoma.

BACKGROUND: Intestinal-type sinonasal adenocarcinoma (ITAC) is a rare tumour related to occupational wood dust exposure. Few studies have described recurrent genetic changes on a genome-wide scale. The aim of this study was to obtain a high resolution map of recurrent genetic alterations in ITAC. MATERIAL AND METHODS: Copy number alterations were evaluated by microarray CGH and MLPA in 37 primary tumours. The results were correlated with pathological characteristics and clinical outcome. RESULTS: Microarray CGH identified the following recurrent aberrations, in descending order: gains at 5p15 (22 cases, 60%), 8q24 (21 cases, 57%), 20q13 (20 cases, 54%), 20q11, and 8q21 (19 cases, 51%), 20p13, and 7p11 (16 cases, 43%), and losses at 5q11-qter, 8p12-pter, and 18q12-23 (15 cases, 40%), and 17p13, and 19p13 (13 cases, 35%). MLPA analysis confirmed this global pattern of gains and losses. Chromosomal loss at 4q32-ter and gains at 1q22, 6p22 and 3q29, as well as deletion of TIMP2 and CRK correlated with unfavourable clinical outcome. CONCLUSION: ITACs have a unique pattern of chromosomal abnormalities. The four different histological subtypes of ITAC appeared genetically similar. Four chromosomal gains and losses and two specific genes showed prognostic value and may be involved in tumour progression.

In utero extracellular dehydration modifies thirst in neonatal rats.

The main aim of this study was to investigate the effect of maternal extracellular dehydration during pregnancy in rats on the development of thirst mechanisms in the offspring. Pregnant rats underwent three episodes of extracellular dehydration induced by injecting s.c. 15ml/kg b.w. of a 20% wt/vol solution of polyethylene glycol (PEG) in saline. The treatment given on days 14, 17 and 20 postconception is thought to induce endocrine and natriophilic responses similar to those elicited by vomiting. The offspring were tested for their responses to three different thirst stimuli at 2, 4 and 6 days of age. Like the controls, the offspring from PEG-treated mothers responded to beta stimulation by isoproterenol at 6 days of age. However, they failed to respond to cellular dehydration (NaCl hypertonic injection) at 2 days of age or to extracellular dehydration by PEG on day 4. In conclusion, offspring exposed to in utero extracellular dehydration do not respond to cellular dehydration at 2 days of age or to extracellular dehydration at 4 days of age, whereas control pups had already developed an appropriate response to these stimuli. According to these results, it therefore seems that in utero conditions determine the development of adaptive thirst responses in offspring.

Maternal RAS influence on the ontogeny of thirst.

Perillan, C., Costales, M., Vijande, M., and J. Arguelles. Maternal RAS influence on the ontogeny of thirst. Physiol Behav XX (X) 000-000, 2006. The main objective of this study was to investigate the effect of an altered ambiance in utero, on the development of thirst mechanisms in the offspring. Female rats underwent a partial ligature of the aorta (PAL), which induces an intrinsic activation of the renin angiotensin system (RAS), thirst and sodium appetite. A second group of female rats was treated with desoxycorticosterone (DOCA) which depresses the RAS. The offspring of these two groups were tested for their responses to several thirst stimuli at 2, 4 and 6 days of age. The offspring from PAL mothers responded like their controls to cellular dehydration (NaCl hypertonic injection) at 2 days of age, and also did to extracellular dehydration by polyethyleneglycol at 4 days. Nevertheless, they responded more to isoproterenol at 6 days of age in comparison to their control group. The offspring from DOCA treated mothers did not show statistically significant responses (in comparison with vehicle injected pups) to hypertonic NaCl at two days nor to polyethyleneglycol at four days. Water intake at 6 days of age after isoproterenol administration in DOCA was statistically enhanced, but not differently from the response obtained from pseudo-DOCA treated pups. In particular, rats developed in a hypereninemic ambiance (O-PAL) during gestation, responded with higher water intake when treated with a strong RAS and thirst activator (isoproterenol) but responded normally to a more gentle and complex stimulus (PG). Therefore it seems that in utero conditions can determine the chronology and intensity of thirst responses in offspring.

Sodium taste threshold in children and its relationship to blood pressure

Popular science has emphasized the risks of high sodium intake and many studies have confirmed that salt intake is closely related to hypertension. The present mini-review summarizes experiments about salt taste sensitivity and its relationship with blood pressure (BP) and other variables of clinical and familial relevance. Children and adolescents from control parents (N = 72) or with at least one essential hypertensive (EHT) parent (N = 51) were investigated. Maternal questionnaires on eating habits and vomiting episodes were collected. Offspring, anthropometric, BP, and salt taste sensitivity values were recorded and blood samples analyzed. Most mothers declared that they added "little salt" when cooking. Salt taste sensitivity was inversely correlated with systolic BP (SBP) in control youngsters (r = -0.33; P = 0.015). In the EHT group, SBP values were similar to control and a lower salt taste sensitivity threshold. Obese offspring of EHT parents showed higher SBP and C-reactive protein values but no differences in renin-angiotensin-aldosterone system activity. Salt taste sensitivity was correlated with SBP only in the non-obese EHT group (N = 41; r = 0.37; P = 0.02). Salt taste sensitivity was correlated with SBP in healthy, normotensive children and adolescents whose mothers reported significant vomiting during the first trimester (N = 18; r = -0.66; P < 0.005), but not in "non-vomiter offspring" (N = 54; r = -0.18; nonsignificant). There is evidence for a linkage between high blood pressure, salt intake and sensitivity, perinatal environment and obesity, with potential physiopathological implications in humans. This relationship has not been studied comprehensively using homogeneous methods and therefore more research is needed in this field.

Sodium taste threshold in children and its relationship to blood pressure.

Popular science has emphasized the risks of high sodium intake and many studies have confirmed that salt intake is closely related to hypertension. The present mini-review summarizes experiments about salt taste sensitivity and its relationship with blood pressure (BP) and other variables of clinical and familial relevance. Children and adolescents from control parents (N = 72) or with at least one essential hypertensive (EHT) parent (N = 51) were investigated. Maternal questionnaires on eating habits and vomiting episodes were collected. Offspring, anthropometric, BP, and salt taste sensitivity values were recorded and blood samples analyzed. Most mothers declared that they added "little salt" when cooking. Salt taste sensitivity was inversely correlated with systolic BP (SBP) in control youngsters (r = -0.33; P = 0.015). In the EHT group, SBP values were similar to control and a lower salt taste sensitivity threshold. Obese offspring of EHT parents showed higher SBP and C-reactive protein values but no differences in renin-angiotensin-aldosterone system activity. Salt taste sensitivity was correlated with SBP only in the non-obese EHT group (N = 41; r = 0.37; P = 0.02). Salt taste sensitivity was correlated with SBP in healthy, normotensive children and adolescents whose mothers reported significant vomiting during the first trimester (N = 18; r = -0.66; P < 0.005), but not in "non-vomiter offspring" (N = 54; r = -0.18; nonsignificant). There is evidence for a linkage between high blood pressure, salt intake and sensitivity, perinatal environment and obesity, with potential physiopathological implications in humans. This relationship has not been studied comprehensively using homogeneous methods and therefore more research is needed in this field.

Thirst changes in offspring of hyperreninemic rat dams.

The aim of this study was to investigate the changes in thirst dependence on the renin-angiotensin system (RAS), in offspring of hyperreninemic, hyperdipsic, and natriophilic rat dams. Female rats underwent a partial aortic ligature between the renal arteries (PAL) or were sham-operated (SHAM). At 6 days of age, offspring of PAL (O-PAL) and SHAM (O-SHAM) dams were injected with isoproterenol (subcutaneously, 500 microg/kg body weight) or vehicle. Pretreatment with captopril (intraperitoneally, 50 mg/kg) on isoproterenol-induced thirst was also studied. Plasma renin activity in dams and hematocrit and osmolality in pups were measured. O-PAL had a greater water intake than O-SHAM. However, they responded similarly to isoproterenol or isoproterenol with captopril pretreatment. Only minor differences in hematocrit and osmolality were found between O-SHAM and O-PAL rats after isoproterenol or vehicle treatment. Beta-adrenergic or angiotensinergic responsivity seems not to be altered in offspring of hyperrenimic, hyperdipsic, and natriophilic dams. Nevertheless, other thirst responses of offspring may be critically dependent upon uterine conditions.

Quantitative histochemical assessment of oxidative metabolism in the subfornical organ after partial aortic ligature in rats.

Circumventricular organs are considered to be involved in hydromineral homeostatic responses. In this study we used quantitative histochemistry of cytochrome oxidase to evaluate the oxidative metabolic activity of the subfornical organ of rats with a partial aortic occlusion. These rats showed a significant increase in water intake from the second day after the ligature, while natriophilia was already significant on the first day. Greater levels of cytochrome oxidase activity were found in subfornical organs of partial aortic ligated rats when compared with control, providing further evidence for the involvement of this circumventricular structure in fluid homeostasis at least in this hyperdipsic, hypernatriophilic, hyperreninemic and hypertensive experimental model.

[Renal effects of prolonged sevoflurane anesthesia in Wistar rats]. / Efectos renales de la anestesia prolongada con sevoflurano en ratas Wistar.

OBJECTIVES: To assess renal safety of sevoflurane administered to Wistar rats at clinical concentrations during prolonged periods of inhalation. MATERIAL AND METHODS: The experimental animals were assigned to two groups of six rats each. Group I received anesthesia with 1.5% sevoflurane for 6 hours and group II received the same concentration of sevoflurane for 15 hours. The anesthesia was inhaled in an open circuit of fresh air at 1 l/min (medicinal air, 22.75% O2). The animals were kept in metabolic cages throughout the nine days the experiment lasted. Weight and urine output were recorded daily and the day before anesthesia was started, inorganic fluoride and blood was analyzed for renal function (urea, sodium, and blood urea nitrogen [BUN]). Between two and three hours after withdrawal of anesthesia, inorganic fluoride was again assessed, and on the last day of the experiment a new blood sample was taken to evaluate renal function. Kidney tissue was then studied. RESULTS: The two groups were similar as to weight, urea, sodium and BUN. Hourly diuresis was significantly greater after anesthesia in group II but not in group I. Inorganic fluoride was significantly higher in both groups, with postanesthetic levels of 22.42 +/- 1.76 microM/l in group I and 35.05 +/- 1.80 microM/l in group II. Renal tissue from both groups appeared normal under an optical microscope. CONCLUSIONS: Sevoflurane at the doses tested increases inorganic fluoride concentrations although for both periods the levels stayed under 50 microM/l, which has been considered the nephrotoxic threshold. No signs of changes in renal function were observed in blood texts or tissue studies.

Effect of castration and gonadal hormones on insulin-induced drinking.

Female Wistar rats in any of the estrual phases have been shown to drink significantly more water than males (p < 0.05), after a single I.P. insulin injection (5 U/kg b.wt.). Sexual differences in insulin-induced drinking persisted after castration when it was made in adult rats (4.6 +/- 1.2 ml/2 h, males = 8; vs. 13.0 +/- 3.1 ml/2 h, females = 8; p < 0.05). On the other hand, when animals were castrated before puberty or when newborn, sexual differences in insulin-induced drinking disappeared. Hence, insulin-induced drinking seems to be a sex-dependent phenomenon that differentiates just before or during puberty since it is abolished by castration prior to sexual maturation. Sex hormone administration in male and female rats castrated at different ages showed a variety of actions on insulin-induced drinking. A pattern emerged showing that androgenized (testosterone treated) rats drank usually less in response to insulin than estrogen-treated rats (independent of their genetic sex). According to the above results, we can conclude that insulin-induced drinking is a phenomenon sensible to gonadal hormones, both by conditioning the differentiation of some physiological structure or mechanisms that underlay drinking behavior in that paradigm and by a direct action on these or other related mechanisms.

Treatment of Bolivian hemorrhagic fever with intravenous ribavirin.

Bolivian hemorrhagic fever (BHF) is a potentially severe febrile illness caused by Machupo virus (family Arenaviridae). Initial symptoms include headache, fever, arthralgia, and myalgia. In the later stages of this illness, patients may develop hemorrhagic manifestations including subconjunctival hemorrhage, epistaxis, hematemesis, melena, and hematuria, as well as neurological signs including tremor, seizures, and coma. During the BHF epidemics of the 1960s, convalescent-phase immune plasma from survivors of BHF was administered to selected patients infected with Machupo virus. However, there is currently a paucity of survivors of BHF who can donate immune plasma, and there is no active program for collection and storage of BHF immune plasma; therefore, we had the opportunity to offer intravenous ribavirin to two of three patients with this potentially life-threatening infection. One patient with laboratory-confirmed Machupo virus infection who received ribavirin recovered without sequelae, as did a second patient with suspected BHF whose epidemiological and clinical features were similar to those of the first patient. This report describes the first use of intravenous ribavirin therapy for BHF in humans, and the results suggest the need for more extensive clinical studies to assess the usefulness of ribavirin for treating BHF.

Poliomyelitis eradication and its impact on primary health care in the Philippines.

Since 1992, the Philippines has conducted four national immunization days (NIDs) for polio eradication. Surveillance for acute flaccid paralysis (AFP) began in 1992. Through good routine immunization, the incidence of paralytic polio had decreased to low levels in the Philippines even before the NIDs were initiated. With continuously improving AFP and virologic surveillance, wild poliovirus has not been isolated since May 1993. NIDs had a direct positive effect on child health through supplementary immunization with oral poliovirus vaccine, measles vaccine, and tetanus toxoid, as well as through the distribution of vitamin A. Following the successful NIDs, the government budget for vaccine purchases increased significantly. Also, the NID strategy was used as a model for several other priority prevention programs of the Department of Health. Through the development of AFP surveillance, polio eradication also helped to improve surveillance for other Expanded Programme on Immunization diseases.

Using cost-effectiveness analysis to evaluate targeting strategies: the case of vitamin A supplementation.

Given the demonstrated efficacy of vitamin A supplements in reducing childhood mortality, health officials now have to decide whether it would be efficient to target the supplements to high risk children. Decisions about targeting are complex because they depend on a number of factors; the degree of clustering of preventable deaths, the cost of the intervention, the side-effects of the intervention, the cost of identifying the high risk group, and the accuracy of the 'diagnosis' of risk. A cost-effectiveness analysis was used in the Philippines to examine whether vitamin A supplements should be given universally to all children 6-59 months, targeted broadly to children suffering from mild, moderate, or severe malnutrition, or targeted narrowly to pre-schoolers with moderate and severe malnutrition. The first year average cost of the universal approach was US$67.21 per death averted compared to $144.12 and $257.20 for the broad and narrow targeting approaches respectively. When subjected to sensitivity analysis the conclusion about the most cost-effective strategy was robust to changes in underlying assumptions such as the efficacy of supplements, clustering of deaths, and toxicity. Targeting vitamin A supplements to high risk children is not an efficient use of resources. Based on the results of this cost-effectiveness analysis and a consideration of alternate strategies, it is apparent that vitamin A, like immunization, should be provided to all pre-schoolers in the developing world. Issues about targeting public health interventions can usefully be addressed by cost-effectiveness analysis.

PIP: It has been established that vitamin A supplementation can help reduce levels of child mortality. Findings are reported from a cost-effectiveness study in the Philippines undertaken to determine whether vitamin A supplements should be given universally to all children age 6-59 months; targeted broadly to children with mild, moderate, or severe malnutrition; or targeted narrowly to preschoolers with moderate and severe malnutrition. Whether to target supplementation depends upon the degree of clustering of preventable deaths, the cost of the intervention, the side effects of the intervention, the cost of identifying the high risk group, and the accuracy of the diagnosis of risk. The first year average cost of the universal approach would be US$67.21 per death averted, $144.12 for the broad targeting approach, and $257.20 for the narrow approach. Targeting vitamin A supplements to high-risk children is therefore not an efficient use of resources. Vitamin A, like immunization, should be provided to all preschoolers in the developing world.

Increased salt preference in adult offspring raised by mother rats consuming excessive amounts of salt and water.

This study was designed to evaluate the effects of an early high-salt environment on the maternal and the young offspring physiology and on the adult offspring sodium appetite. Twenty-five-adult female Wistar rats were pseudorandomly divided into two groups. Twelve animals underwent a partial ligature of their abdominal aorta (PAL). Once polydipsia and sodium appetite (tested by measuring water and a 2.7% NaCl intakes) developed, they were mated. The other 13 rats (SHAM) were sham-operated and also mated. Throughout pregnancy and lactation, water and salt intake of PAL rats was consistently and significantly higher than that of the Sham. On gestation day 20, amniotic fluid and maternal plasma sodium concentration of PAL and Sham rats did not differ. Sodium concentration in the milk of the lactating PAL group was elevated (P < 0.05) on day 20 after delivery. At 0, 10 and 21 days of age, plasma sodium concentration of PAL offspring (PAL-O) and Sham offspring (Sh-O) were not significantly different. At 90 days of age, the salt preference of PAL-O rats was greater than that of Sh-O rats after 7 days of sodium deprivation (P < 0.01).

Changes of blood pressure responsiveness in rats exposed in utero and perinatally to a high-salt environment.

We tested the hypothesis that the pressor responses to angiotensin II could be influenced by an early salt exposure. Twenty-five adult female rats were pseudorandomly divided in two groups. Twelve animals underwent a partial ligature of their abdominal aorta (PAL). Once polydipsia and sodium appetite developed, these rats were mated. The other group (13 rats) was sham-operated (Sham) and mated. Throughout pregnancy and lactation, water and 2.7% NaCl solution intakes differed between the two groups of mother rats. PAL offspring (PAL-O; n = 14), and Sham-operated offspring (Sh-O; n = 10), were maintained on a solid diet containing 1% NaCl, tap water and a 2.7% NaCl solution. At 90 days of age, pressor responsiveness to intravenous angiotensin II (50, 100 and 200 ng) was assessed in anesthetized rats. The pressor responses to 50 and 200 ng angiotensin II were significantly greater in PAL-O rats than in Sh-O rats. These results support the hypothesis of a modulation of cardiovascular responsiveness or its underlying mechanisms by an early high salt environment.

Factors influencing the return to work of patients after hip replacement and rehabilitation.

OBJECTIVE: To determine the incidence of medical and sociocultural factors on the return to work of patients after hip replacement and rehabilitation treatment. DESIGN: Case review. Frequency and association of variables' analysis. SETTING: The rehabilitation unit of a general hospital in Oviedo (Spain). This setting is a part of an institutional referral center and is the only state-owned hospital that provides rehabilitation treatment for hospitalized patients from a rural and urban area of about 1,000,000 inhabitants. PATIENTS: 747 patients of both sexes, all of them working before receiving treatment, age range 18 to 64 years. MAIN OUTCOME MEASURES: Relationship of several variables: age, sex, habitat, level of education, type of work, underlying illness, walking ability, pain, and type of social security versus return to work. RESULTS: At discharge, 25% of patients return to work. There is a significant association (p < .001) between return to work and any of the following variables: underlying illness, kind of work, walking ability, habitat, and educational level. CONCLUSION: This physiopathology of symptoms and signs of the patients is not the unique indicator of whether a person will continue working after hip replacement and rehabilitation treatment. Extramedical factors, such as social status, kind of work, and cultural background, are very influential.

Transcranial oblique lateral radiography to verify the position of the mandibular condyles with the use of functional appliances.

By means of standardized transcranial oblique lateral (TOL) radiographs, the position of the mandibular condyles in the glenoid fossae of 14 patients with Class II division 1 malocclusion was studied at the beginning of treatment with or without functional appliances placed in position, and also at the end of treatment. A significant increase in the distance between the upper point of the condyle and the glenoid fossa was found when the appliance was worn for the first time. This displacement was found to disappear at the end of the treatment even when the appliance was placed in position.

Standardized diagnosis of pneumonia in developing countries.

The World Health Organization recommends the use of raised respiratory rate and chest wall indrawing to enable health workers in developing countries to diagnose pneumonia. We evaluated the current World Health Organization guidelines for management of the child with cough or difficult breathing in Manila, Philippines and Mbabane, Swaziland using an identical protocol in both countries. Raised respiratory rate was defined as greater than or equal to 50/minute for children ages 2 to 12 months and greater than or equal to 40/minute for children 12 months to 5 years. Chest wall indrawing was defined as inward movement of the bony structures of the lower chest wall with inspiration. In the Philippines raised respiratory rate or chest wall indrawing, when applied by a pediatrician, was found to have a sensitivity of 0.81 and specificity of 0.77 for predicting pneumonia as determined by a pediatrician with the aid of a chest roentgenogram. In Swaziland the sensitivity was 0.77 and the specificity was 0.80. When applied by health workers the sensitivity was similar but the specificity was lower. The current World Health Organization ARI case management guidelines predicted pneumonia with similar sensitivity and specificity in two very different developing countries, the Philippines and Swaziland.

Attenuation of insulin-induced drinking by beta-adrenoceptor antagonists.

Insulin-induced drinking (IID) in male Wistar rats, evoked by administering 5 U/kg of crystalline porcine insulin i.p., was significantly decreased by propranolol (0.1 and 0.5 mg/kg s.c.) after 1 and 2 h. The blood glucose of rats treated with a much higher dose of propranolol (10 mg/kg body weight) and insulin did not differ from that of rats treated solely with insulin after 30 and 120 min. Atenolol (0.5 mg/kg s.c.) caused a reduction in IID after 1 and 2h. Butoxamine (1 mg/kg s.c.) also reduced IID after 1 and 2h, and at 0.5 mg/kg after 1h. The alpha-blocker, phenoxybenzamine (10 mg/kg s.c.), had the opposite effect, stimulating IID after 2h. There is no direct evidence that insulin activated the sympathetic system at the doses used in these experiments. Nevertheless, the results reported here seem to be compatible with the involvement of the sympathetic system in IID, possible through the renin-angiotensin system.

Psychological aspects of insulin-induced thirst.

Fifteen normal volunteers received one insulin injection or saline in two nonconsecutive days. At 0', 30', 60' and 90' water intake was measured. Simultaneously subjective thirst and hunger were recorded by running a set of psychological tests. Water intake was higher after insulin than saline at 60' and 90'. Insulin increases thirst sensation even before the sensation of hunger.

Insulin stimulation of water intake in humans.

Drinking response to the intravenous administration of insulin (0.1 U/kg) was studied in 15 volunteers (eight males and seven females). Water intake was significantly higher after insulin than after saline administration during the 90-min period studied. Plasma glucose decreased significantly in individuals receiving insulin and the time of the maximum decrease (30 min) was concurrent with the beginning of water intake. Haematocrit values in the insulin-treated group were also significantly higher at that time. Plasma renin activity (PRA) after insulin administration was higher than under basal conditions or after saline injection. On the other hand, psychological responses indicated that insulin probably elicits thirst prior to the hunger which appears with hypoglycaemia. A possible role of endogenous insulin in meal-related thirst is hypothesized.