Systemic activity and mortality in primary Sjögren syndrome: predicting survival using the EULAR-SS Disease Activity Index (ESSDAI) in 1045 patients.

OBJECTIVE: To score systemic activity at diagnosis and correlate baseline activity with survival in a large cohort of patients with primary Sjögren syndrome (SS). PATIENTS AND METHODS: We include 1045 consecutive patients who fulfilled the 2002 classification criteria for primary SS. The clinical and immunological characteristics and level of activity (EULAR-SS Disease Activity Index (ESSDAI) scores) were assessed at diagnosis as predictors of death using Cox proportional hazards regression analysis adjusted for age at diagnosis. The risk of death was calculated at diagnosis according to four different predictive models. RESULTS: After a mean follow-up of 117 months, 115 (11%) patients died. The adjusted standardised mortality ratio for the total cohort was 4.66 (95% CI 3.85 to 5.60), and survival rates at 5, 10, 20 and 30 years were 96%, 90%, 81% and 60%, respectively. The main baseline factors associated with overall mortality in the multivariate analysis were male gender, cryoglobulins and low C4 levels. Baseline activity in the constitutional, pulmonary and biological domains was associated with a higher risk of death. High activity in at least one ESSDAI domain (HR 2.14), a baseline ESSDAI score ≥14 (HR 1.85) and more than one laboratory predictive marker (lymphopenia, anti-La, monoclonal gammopathy, low C3, low C4 and/or cryoglobulins) (HR 2.82) were associated with overall mortality; these HRs increased threefold to 10-fold when the analysis was restricted to mortality associated with systemic disease. CONCLUSIONS: Patients with primary SS, who present at diagnosis with high systemic activity (ESSDAI ≥14) and/or predictive immunological markers (especially those with more than one), are at higher risk of death.

Influence of physical training on the Syrian hamster's melatonin rhythm.

Melatonin secretion can be influenced by acute exercise. Using female Syrian hamsters we assessed the influence of physical exercise in the serum melatonin rhythm. Melatonin concentrations were determined by RIA. After a gradually increased training program in which experiments were performed at the end of the light phase of the photoperiod (14-h light:10-h dark; lights on at 21:00) animals were killed immediately after exercise (14 h light) and at different time points including 11h after light and 3, 6, 8 and 9h after dark. No differences in melatonin concentrations immediately after exercise practice between control and trained animals were observed. A slower melatonin nighttime increase in exercised hamsters, with significantly lower levels 6h after dark in comparison with controls was found. The peak value appeared 8h after dark but high melatonin levels were prolonged in exercised hamsters, showing significantly higher melatonin levels 9h after. In conclusion, our results indicate for the first time that Syrian hamsters submitted to a training program of increased activity at the end of the light phase, the rest period, showed an altered melatonin rhythm, resembling the response observed in humans.

Prenatal melatonin and its interaction with tachykinins in the hypothalamic-pituitary-gonadal axis.

The pineal gland, through its hormone melatonin, influences the function of the hypothalamic-pituitary-gonadal axis. Tachykinins are bioactive peptides whose presence has been demonstrated in the pineal gland, hypothalamus, anterior pituitary gland and the gonads, in addition to other central and peripheral structures. Tachykinins have been demonstrated to influence the function of the hypothalamic-pituitary-gonadal axis, acting as paracrine factors at each of these levels. In the present review, we examine the available evidence supporting a role for melatonin in the regulation of reproductive functions, the possible role of tachykinins in pineal function and the possible interactions between melatonin and tachykinins in the hypothalamic-pituitary-gonadal axis. Evidence is presented showing that melatonin, given to pregnant rats, influences the developmental pattern of tachykinins in the hypothalamus and the anterior pituitary gland of the offspring during postnatal life. In the gonads, the effects of melatonin on the tachykinin developmental pattern were rather modest. In particular, in the present review, we have included a summary of our own work performed in the past few years on the effect of melatonin on tachykinin levels in the hypothalamic-pituitary-gonadal axis.

How are we treating our systemic patients with primary Sjögren syndrome? Analysis of 1120 patients.

OBJECTIVE: To describe how systemic disease is treated in a large cohort of Spanish patients with primary Sjögren syndrome (pSS) in daily practice, focusing on the adequacy of therapies for the level of systemic activity measured by ESSDAI score. PATIENTS AND METHODS: By December 2014, our database included 1120 consecutive patients who fulfilled the 2002 classification criteria for SS. Therapeutic schedules were classified into 4 categories: no systemic therapies, hydroxychloroquine (HCQ) and/or low dose glucocorticoids (GCS) (<20mg/day), high dose GCS (>20mg/day) and use of second-line therapies (immunosuppressive agents, intravenous immunoglobulins [IVIG] and/or rituximab [RTX]). RESULTS: There were 1048 (94%) women and 72 (6%) men , with a mean age at diagnosis of 54 years. The main drug-based therapeutic approaches for systemic pSS during follow-up were HCQ in 282 (25%) patients, GCS in 475 (42%, at doses >20mg/day in 255-23%), immunosuppressive agents in 148 (13%), IVIG in 25 (2%) and RTX in 35 (3%) patients. HCQ was associated with a lower risk of death (adjusted HR of 0.57, 95% 0.34-0.95). We classified 16 (7%) of the 255 patients treated with >20mg GCS and 21/148 (14%) treated with immunosuppressive agents as patients inadequately treated, mainly associated with articular involvement of low/moderate activity. CONCLUSION: The management of pSS should be organ-specific, using low dose GCS in patients with moderate systemic activity, limiting the use of high dose GCS and second-line therapies to refractory or potentially severe scenarios. The use of systemic therapies for dryness, chronic pain or fatigue is not warranted.

Ageing and melatonin influence on in vitro gonadotropins and prolactin secretion from pituitary and median eminence.

The effect of ageing and/or melatonin (MEL) on in vitro gonadotropins, luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (PRL) release and tissue content from pituitary and median eminence (ME) were investigated. Gonadotropins and PRL basal release (I-1) from hemipituitaries of young cyclic-rats was decreased by MEL to levels shown in old acyclic rats. Pituitary tissue content of LH and PRL were not affected by ageing or MEL treatment. However, pituitary FSH tissue content was decreased by ageing and MEL, suggesting a different regulatory mechanism. MEL inhibitory influence on pituitary hormones is mainly exerted on the secretory process. This effect is only exerted in young rats. ME LH and PRL release and content were significantly lower than in pituitary. However, FSH release and content in ME showed values similar to those found in the pituitary. This study confirms that the functional capacities of pituitary gland and ME are maintained during reproductive senescence.

In vitro pituitary responsiveness to LHRH in young and old female rats. Influence of melatonin.

The effect of aging and melatonin on in vitro pituitary responsiveness to luteinizing hormone-releasing hormone (LHRH) was studied. Young cyclic (3-months-old) control (cyclic-control, N = 15), and melatonin (MEL) treated for 2 months (150 microg/100 g BW) (cyclic-MEL, N = 15), old acyclic (23-months-old) control (acyclic-control, N = 13), and MEL-treated (acyclic-MEL, N = 18) rats were used. The hormones analyzed were luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (PRL). The results showed a different influence of the reproductive status as well as of melatonin on the basal secretion rate of both gonadotropins, i.e. LH and FSH. Only the basal FSH release was significantly reduced in cyclic-MEL and acyclic-controls compared to cyclic-controls. The hemipitutary FSH content raised to values similar to those observed for FSH secretion and only the cyclic-MEL group showed significantly higher FSH pituitary content than for release. LHRH addition to the incubation medium resulted in increased LH release for both cyclic and acyclic rats, but FSH release was only stimulated in acyclic rats. Melatonin treatment blunted this response in both cases. In addition, melatonin treatment inhibited prolactin release in acyclic-MEL group after LHRH stimulation but not the basal levels. Pituitary LH and prolactin contents, were significantly higher than the pituitary LH and prolactin levels released from all groups studied, and were not affected by reproductive senescence nor by exogenous melatonin. These data indicate that aging influences more the secretory than the biosynthetic processes. Melatonin influences is endocrine status-dependent, being inhibitory when pituitary hormones reach their higher values.

Vertebral involvement in hyperphosphatemic tumoral calcinosis.

Hyperphosphatemic tumoral calcinosis (HTC) is an inherited metabolic disorder characterized by calcified soft tissue masses and hyperphosphatemia. Besides these typical features, a number of less common manifestations have been reported, all of them related to pathologic calcification of various tissues. We have investigated the case of a woman with hyperphosphatemia, recurrent episodes of lumbar pain, and a positive familial history of HTC. A bone scan showed markedly increased uptake in the lower lumbar spine. Magnetic resonance imaging showed pathological changes in L5 compatible with an inflammatory reaction and not suggestive of neoplastic process. There was no evidence of infection, trauma, malignancy, or other disease that could cause the lesion. We treated the patient with analgesics and NSAIDs and the pain remitted over a period of 1 week. In a follow-up magnetic resonance imaging 7 months later, the L5 lesion had disappeared completely. A computed tomography scan analysis with a bone window showed a sclerotic area at the L5 vertebral body. We believe that this patient was affected by the syndrome of HTC and that the inflammatory phenomena found in L5 are a manifestation of this disease.

Effect of pinealectomy and melatonin treatment during pregnancy on the sexual development of the female and male rat offspring.

Sexual development of female and male rat offspring of control, pinealectomized (PIN-X) or melatonin (MEL 250 micrograms/100 g body wt)-treated mother rats during pregnancy was studied. Newborns were studied at the following phases of sexual development: neonate (5 days old), infantile (15 days old), juvenile (25 and 30 days old) and pubertal phase (55 days). In female offspring, MEL treatment during pregnancy significantly increased plasma luteinizing hormone (LH) in 15- and 25-day-old rats; however, at the end of the prepubertal period (30 days) the concentration of plasma LH decreased significantly as compared to control rats. This hormonal pattern was different from that observed in offspring of control and PIN-X rats, which had low LH levels at 25 days of age and higher LH levels at 30 days of age. Follicle-stimulating hormone (FSH) did not vary significantly among the three groups. Plasma prolactin levels were affected by PIN-X of the mother, showing significantly higher levels in the 5-day-old offspring than in the controls; plasma prolactin levels were also affected by MEL treatment of the mother, producing hyperprolactinemia in the 30-day-old female offspring. In male offspring, sexual development in control male rats progressed rapidly with significantly increased LH and FSH levels at 25 and 30 days compared to those measured during the neonatal and infantile periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Developmental pattern of tachykinins during aging in several organs: effect of exogenous melatonin.

Mammalian neurokinin A (NKA) and substance P (SP) are neuropeptides widely distributed in the body; they are potential regulators of the basal blood flow and therefore of the function of many organs and tissues. In the present investigation, we studied the age-dependent changes in NKA and SP in ovary, liver, pancreas and spleen as well as the role of exogenous melatonin on these changes. Female rats of 5, 15 or 25 months of age were studied. In the ovary, NKA concentrations did not change during aging. SP concentrations in the control group were significantly higher (P<0.01) in old rats than in the other two age groups studied. Melatonin treatment resulted in reduced concentrations as compared with those of the control old rats. In the pancreas, NKA and SP concentrations increased during aging, the young rats showing significantly lower values (P<0.01) than middle-aged and old rats for NKA and significantly lower (P<0.01) than the old rats for SP. After melatonin treatment the differences in NKA concentrations disappeared and SP decreased in middle-aged as compared with those in old rats. In the liver, NKA and SP concentrations in the control and melatonin-treated groups did not differ significantly for the three age groups studied. Splenic NKA in control and melatonin-treated groups increased from young to middle-age up to old ages. SP concentrations showed similar values at all ages except in melatonin-treated old rats; in these animals there were significantly higher concentrations than in young melatonin-treated rats. The effect of melatonin was mainly observed on the ovary and pancreas in old rats, with a reduction in the concentrations as compared with those observed in the young groups.

Seasonal changes of SP and NKA in frontal cortex, striatum and testes in the rat. Role of maternal pineal gland.

The concentrations of neurokinin A (NKA) and substance P (SP), members of tachykinins family, have been studied in all seasons of the year in frontal cortex, striatum and testes of male offspring 21-, 31-, or 60 days old of mother Wistar rats: control, pinealectomized (PIN-X) and pinealectomized + melatonin during pregnancy (PIN- X + MEL) kept under 12h:12h L:D. Control-offspring: in spite of having been kept under constant environmental conditions throughout the year, had marked differences in tachykinin concentrations. The highest tachykinin concentrations in the frontal cortex were found in summer and fall and the lowest in winter and spring. Maternal PIN-X resulted in alterations of this developmental pattern, mainly in PIN-X- and PIN- X + MEL-offspring in which the highest tachykinin concentrations at 21 and 31 days of age were only observed during summer. The alterations were observed up to 60 days of age for both tachykinins, when at this age control-offspring showed similar NKA concentrations. Seasonal variations were still observed in PIN-X- and PIN- X + MEL-offspring. In striatum and testes no mayor modifications throughout the four seasons of the year were found, with very few exceptions. PIN-X did not alter tachykinin concentrations, neither treatment with melatonin did it. In conclusion, our data clearly indicate for the first time that NKA and SP do indeed have seasonal rhythms in frontal cortex and that the maternal pineal gland plays a role in their entrainment already during fetal life.

Prenatal melatonin influences developmental changes of tachykinins in response to estradiol benzoate.

The developmental changes of hypothalamic, pituitary, striatum and pineal gland tachykinin concentrations, as well as the response to estradiol-benzoate (EB) administration, were studied in offspring of control and melatonin (MEL) treated mother rats. Female rats were studied throughout different phases of the sexual development: infantile, prepubertal and pubertal periods, in the four following groups; control-offspring+vehicle; control-offspring+EB; MEL-offspring+vehicle; MEL-offspring+EB. Hypothalamic NKA in control-offspring+ vehicle was significantly increased only at 27 days of age and in control-offspring+EB at 27 days of age and during the infantile period. Hypothalamic SP levels increased similarly in control-offspring+EB during the infantile period but the EB influence was more pronounced with significantly increased concentrations at 32 days of age. Prenatal melatonin treatment produced major alterations in these patterns of postnatal development. In MEL-offspring+EB tachykinins concentrations in the hypothalamus during infantile and prepubertal periods did not increase, however at 37 days of age, they showed significantly higher values than in control-offspring+EB groups. The developmental pattern of pituitary NKA and SP concentrations in both; control-offspring+vehicle and control-offspring+EB groups, showed similar values from the infantile period to puberty, indicating that NKA and SP concentrations remained at similar levels independently of the sexual stage, only at 27 days of age in control-offspring+EB significantly increased values were found as compared to MEL-offspring+EB. Prenatal melatonin did not produce marked modifications, only significantly lower NKA and SP concentrations in MEL-offspring+EB group were observed at 25 days of age in comparison to control-offspring+EB group. Striatal NKA and SP concentrations showed a similar developmental pattern. In control-offspring, EB treatment produced NKA and SP decreased concentrations at the infantile period than in control-offspring+vehicle and significantly increased concentrations during the prepubertal period, then during the pubertal period NKA and SP concentrations decreased in control-group+EB. However, prenatal melatonin treatment reduced the levels of striatal NKA and SP during the prepubertal period after EB treatment and delayed until pubertal period the increase previously observed in control group during the prepubertal period. In MEL-offspring+vehicle group striatal concentrations of both tachykinins remained at low levels from infantile period until pubertal period. Prenatal melatonin and EB did not produce major alterations in SP pineal concentrations throughout sexual development. Plasma estradiol concentrations were significantly higher in the groups that received EB treatment than in those that received vehicle during prepubertal and juvenile periods in control-offspring+EB group and during the pubertal period in MEL-offspring+EB group. These data indicate that prenatal MEL treatment may influence NKA and SP developmental pattern from the infantile period until adulthood in the female rat.

Developmental changes of hypothalamic, pituitary and striatal tachykinins in response to testosterone: influence of prenatal melatonin.

Substance P (SP) and neurokinin A (NKA), members of the family of mammalian tachykinins, are involved in the regulation of many physiological functions and are widely distributed in mammalian tissues. In this report, the effects of prenatal melatonin on the postnatal developmental pattern of NKA, and SP, and on testosterone secretion were investigated. Also, tachykinin response to the administration of testosterone propionate (TP) was studied. The brain areas studied were medio-basal-hypothalamus, pituitary gland and striatum. Male rat offspring of control or melatonin treated mother rats were studied at different ages of the sexual development: infantile, juvenile or prepubertal periods, and pubertal period. Both groups received exogenous TP (control-offspring+TP and MEL-offspring+TP), or the vehicle (control-offspring+placebo and MEL-offspring+placebo). Hypothalamic concentrations of all peptides studied in control-offspring+placebo remained at low levels until the juvenile period, days 30-31 of age. After this age, increasing concentrations of these peptides were found, with peak values at puberty, 40-41 days of age, then declining until adulthood. In the MEL-offspring+placebo a different pattern of development was observed; hypothalamic concentrations of NKA and SP from the infantile period until the end of juvenile period were significantly higher than in control-offspring+placebo. TP administration exerted a more marked influence on MEL-offspring than on control-offspring and prevented the elevation in tachykinin concentrations associated with prenatal melatonin treatment. TP administration to control-offspring resulted in significantly reduced (P < 0.05) tachykinin concentration only at 40-41 days of age, and increased (P < 0.01) during infantile period as compared to control-offspring+placebo. Pituitary NKA concentrations were lower than in the hypothalamus. In control-offspring+placebo pituitary NKA levels did not show significant changes throughout sexual development. A different developmental pattern was observed in MEL-offspring+placebo, with significantly increased (P < 0.05) pituitary NKA concentrations at 35-36 days of age than in control-offspring+placebo. TP administration to control-offspring influenced pituitary NKA levels at the end of the infantile and pubertal periods, showing at both stages significantly higher (P < 0.05) NKA levels as compared to control-offspring+placebo. NKA levels in MEL-offspring+TP were only affected at 21-22 days of age, showing significantly increased (P < 0.01) values as compared to MEL-offspring+placebo. Striatal tachykinin concentrations in control-offspring did not undergo important modifications throughout sexual development, but during the prepubertal period they started to increase. Maternal melatonin and TP injections produced short-lived alterations during the infantile period. The results showed that prenatal melatonin delayed the postnatal testosterone secretion pattern until the end of the pubertal period and postnatal peptide secretion in brain structures. Consequently, all functions depending of the affected areas will in turn, be affected.

Influence of maternal pineal gland on the developmental pattern of neurokinin A (NKA) and substance P (SP) in male-rat-offspring: relationship to the season of the year.

The present study examines the influence of maternal pineal gland on the frontal cortex, striatal and testicular concentrations of the tachykinins, neurokinin A (NKA) and substance P (SP). Control, pinealectomized (PIN-X) and PIN-X plus melatonin-treated (PIN-X + MEL) mother rats were prepared. Male offspring rats were studied at 21, 31 and 60 days of age, during the four seasons of the year. In control-offspring tachykinin concentrations in frontal cortex were found at their highest levels in 21-day-old rats with a moderate decrease up to 60 days of age. This developmental pattern was season-dependent, observed only during summer and fall. Maternal PIN-X or PIN-X + MEL resulted in alterations in the offspring, showing during spring and summer significantly higher concentrations (P < 0.01) and during fall significantly lower concentrations of tachykinins in the frontal cortex (P < 0.05, P < 0.01) as compared to control-offspring. The tachykinin concentration in the striatum of control-offspring showed no major modifications throughout the ages studied in the four seasons of the year. With very few exceptions, PIN-X- and PIN-X + MEL did not alter tachykinin concentrations in striatum. Testicular SP concentrations showed a decrease from 21 to 60 days of age. PIN-X or PIN-X + MEL only caused minor and inconsistent modifications in testicular SP levels. In conclusion, our data clearly indicate for the first time that the maternal pineal gland participates in the regulation of the postnatal tachykinin development in some areas of the central nervous system. This effect was more evident in the frontal cortex than in the striatum and testes.

Effect of the lack of melatonin signal on the O2 uptake in sexual nervous structures in male rats.

The effect of the absence of melatonin signal, induced by pinealectomy as well as by continuous light to the oxidative metabolism of nervous structures of the male rat was studied. The selected nervous tissues structures involved in sexual processes of the male rat were amygdala, ventral hypothalamus, septal area pituitary and posterior cortex (latero-occipital); the anterior cortex (latero-frontal) was studied as the control brain area of the rat's sexual activity, while the testes were also studied. Oxidative metabolism was determined by its O2 uptake (QO2) in these tissues. Four groups of rats were studied viz., controls killed during daytime (7 h after lights on), controls killed at night time (5 h after lights off), pinealectomized rats killed during daytime, and male rats kept under constant lighting from birth. The results did not show statistically significant differences of the QO2 (microliters O2/mg wet tissue/h) in the nervous structures involved in sexual processes or in the testes of the rat subjected to pinealectomy or continuous light. Only the QO2 of the anterior cortex showed significant difference (P < 0.05) between day time and night time values of the control group. The pineal gland weight showed a suppressive effect produced by continuous light from birth compared to control group values during the day (P < 0.05) and at night (P < 0.01). The results of this study indicate that the inhibitory effect of the pineal gland on the neuroendocrine reproductive axis of the rat is due to a longer increased nocturnal peak of melatonin, and that the lack of the pineal gland has no effect on the functional activity of nervous structures involved in sexual processes of the rat.

In vitro pituitary prolactin, growth hormone and follicle stimulating hormone secretion during sexual maturation of female rats primed with melatonin.

The influence of in vivo melatonin administration on in vitro pituitary follicle stimulating hormone (FSH), growth hormone (GH) and prolactin secretion, as well as the possible influence of dopamine (DA) were evaluated in prepubertal (31-day-old), pubertal (33-day-old) and adult female rats at diestrus phase of the sexual cycle. The in vitro pituitary hormone secretions were evaluated at basal rate for the first hour of incubation only, in Krebs Ringer phosphate (KRP) (I1) and after a second hour of incubation with KRP (I2) or with KRP+DA (I2 plus DA). I1PRL secretion was significantly higher in 33-day-old control and melatonin treated (MEL) rats as compared to I2 periods. However, in 31-day-old rats I1 secretion was higher than in the I2 or I2+DA periods, in MEL rats. In vitro GH secretion was significantly higher at I1 than during I2 periods in the control 31- and 33-day-old groups, but not in MEL rats. The only significant effect of DA was the elevation of GH in prepubertal MEL rats. In vitro FSH release was increased by melatonin in 31- and 33-day-old female rats. No differences in PRL, GH and FSH secretion were found in adult rats. In conclusion, the results show that melatonin effects upon in vitro pituitary gland activity are reproductive-stage-dependent modifying the secretory capacity of the lactotrop, gonadotrop and somatotrop during prepubertal and pubertal ages but not in adult rats studied at a quiescent phase of the sexual cycle.

[Epidemiology of hip fracture in Asturias]. / Epidemiología de la fractura de cadera en Asturias.

BACKGROUND: Hip fracture is the complication with the greatest medical repercussions in osteoporosis. The aim of this study was to know both the incidence of osteoporotic hip fracture in Asturias, Spain and the immediate evolution of these patients. METHODS: The clinical histories of all the patients admitted for hip fracture in 1992 in two Asturian public health care areas were reviewed. Hip fractures in patients under the age of 45 years or those occurring because of other diseases (metastasis, serious injury) were excluded. RESULTS: In the health care areas studied in 1992 there were 283 osteoporotic hip fractures with an incidence of 219.6 fractures/10(5) inhabitants/year in those over the age of 50 years. The incidence in women over 45 years of age was 3-fold greater than that in men of the same age. The mean age of the patients was 80.2 +/- 8.9 years. The incidence in people over the age of 50 was greater in urban (266/10(5) inhab./year) than in the rural areas (185.7/10(5) inhab./year) (p < 0.001). Ten percent of the patients were residing in old age residences or hospitals at the time of the fracture. Eighty-one percent required surgery. Home was the site of the fracture in 84% of the cases with no seasonal variation being observed. The most frequent intrahospitalary complications observed were infections (15%), cardiac or respiratory disturbances (18%), and confusion (8%). The mean hospital stay was 26.5 days with acute hospitalary mortality of 5.6%. Nineteen point seven percent of the patients were transferred to a center for chronically ill people. The total cost of the hospital care for the hip fractures in this study exceeded 311 million pesetas in 1992. CONCLUSIONS: The epidemiology of osteoporotic hip fracture in Asturias, Spain, follows a similar pattern as that found in other Spanish regions. It was found to be more frequent in the urban than in the rural areas. Hospitalary mortality of these patients is partly determined by age and the number of complications which developed during hospital stay. The impact on the patients with osteoporotic hip fracture and on the economic resources destined to their attention justifies the development of osteoporosis and fracture prevention programs.

[What is the opinion of Spanish internists on osteoporosis?]. / 'Qué opinan los internistas españoles de la osteoporosis?

OBJECTIVE: To conduct an opinion survey on osteoporosis in Spanish internists. METHOD: Survey sent by mail and by personal visit to members of the Spanish Internists Society. Collection of data on opinion on the disease, diagnostic and therapeutic attitude and means available (general laboratory analyses, conventional radiology, biochemical markers of bone remodeling, densitometry and ultrasounds) and preference when choosing a certain treatment. RESULTS: A total of 538 internists answered. More than 90% of those surveyed consider that osteoporosis is a disease that should be treated by internists. A total of 93% consider that osteoporosis is a prevalent disease. More than 80% have access to densitometry. CONCLUSIONS: The majority of Spanish internists consider that osteoporosis is a disease that should be treated by internists and that it is a disease that enters into their action scope. In general, they have the means necessary for its study and treatment. Bisphosphonates constitute the drug of choice and calcium and vitamin D supplements are indicated in almost all the cases.

[Blood levels of phenytoin. Pharmacokinetics and individualization of dosages in controlled children with crises and with persistence of crises]. / Niveles séricos de fenitoína. Farmacocinética e individualización de dosis en niños con crisis controlados y con persistencia de las crisis.

The pharmacokinetics of phenytoin was evaluated using the Michaelis-Menten technique in children with seizures seen at the Outpatient Ward, in order to adjust their medication dosages based on a clinical-pharmacological relation. The children were divided into two groups: Group A (controlled seizures) and group B (persistent seizures). Each group of children were orally given 7 mg/kg of phenytoin. Their serum levels were measured using enzymatic immunoassay at one, two, four, eight and 12 hours after taking the medication. There was a significant correlation (P less than 0.05) between the average saturation constant (Km) and the maximum speed (Vmax) with age and the doses administered in group A, which showed a lesser metabolic capacity than group B. There was also a significant correlation (P less than 0.05) when predicting the levels in each group. Clinically, the patients group A were controlled while those in group B witnessed a lesser frequency and intensity of the seizures in six patients, two were controlled and two others remained the same. The data shows a clinical-pharmacological correlation in children difficult to control, and improves the dosaging criteria used each individuals needs.