Rehabilitación neuromotora en unidades de tratamiento del ataque cerebrovascular / Neuromotor rehabilitation in stroke treatment units

RESUMEN: Introducción: El Ataque Cerebro Vascular (ACV) es la segunda causa de muerte a nivel mundial y primera causa de discapacidad en el adulto. Su complejidad requiere de una atención integral a través de un equipo multiprofesional, implementado en las denominadas Unidades de Tratamiento del Ataque Cerebrovascular (UTAC). Considerando su relevancia e impacto en el pronóstico, es fundamental conocer las acciones desarrolladas en el ámbito de la rehabilitación neuromotora en estas unidades, información que actualmente es limitada. Método: Estudio descriptivo de corte transversal, la muestra fue por conveniencia, participaron 5 kinesiólogos de establecimientos públicos de salud. La recolección de información se realizó con una encuesta en línea enfocada a las acciones que se realiza en la UTAC. El análisis de datos se realizó con STATA 15 y ATLAS TI 8.0. Resultados: El inicio y frecuencia de la rehabilitación neuromotora es variable, ocurre entre las 24 y 48 horas posterior al diagnóstico. Diariamente se realizan entre una a tres sesiones por usuario, su duración varía desde 25 a 90 minutos. Las acciones neuromotoras son de carácter integral y multiprofesional, el abordaje incluye el componente neuromotor, respiratorio y estado cognitivo. Las acciones neuromotoras incorporan técnicas de facilitación de la postura más alta lograda por el usuario y estimulación sensorial, entre otras. Conclusiones: La rehabilitación neuromotora en las UTAC de Chile muestra realidades diferentes en cuanto a la identificación, funcionamiento y la intervención neuromotora.

ABSTRACT Background: Stroke is the second leading cause of death in the world and the first cause of disability in adults. Its complexity requires comprehensive care provided by a multiprofessional team, implemented in the so-called Stroke Treatment Units (STUs). In view of their relevance and impact on the prognosis, identifying activities developed in the framework of neuromotor rehabilitation is of fundamental importance, information which, at present, is not readily available. Methods: Cross-sectional descriptive study, convenience sampling with the participation of 5 kinesiologists from public health centers in Chile. Information was collected by means of an online survey focused on the work being carried out in the STUs. Data analysis was performed using STATA 15 and ATLAS TI 8.0 software. Results: Initiation and frequency of neuromotor rehabilitation is variable and occurs between 24 and 48 hours after diagnosis. Between one and three daily sessions per user are performed and their duration varies from 25 to 90 minutes. Neuromotor activities are integral and multiprofessional; the approach includes neuromotor, respiratory and cognitive components. Neuromotor activities incorporate facilitation techniques for the most advanced user posture achieved and sensory stimulation, among others. Conclusions: Neuromotor rehabilitation in Chile´s STUs shows different realities in terms of identification, functioning and neurokinetic intervention.

[Registry of perioperative cardiac arrests in a clinical hospital in the period 2006-2017]. / Registro de paro cardiorrespiratorio perioperatorio en un hospital universitario en el período 2006-2017.

BACKGROUND: Perioperative cardiac arrest (PCA) is a rare but important event in the operating room. AIM: To describe PCA events at a Clinical Hospital in Santiago, Chile. MATERIAL AND METHODS: Registry of PCA that occurred in the operating room (OR) and during procedures not carried out in the OR between September 2006 and November 2017. Precipitating events, type of anesthesia and results of resuscitation maneuvers were described. RESULTS: Eighty events (five outside of the OR) during 170,431 surgical procedures were recorded, resulting in an incidence of 4.4 events per 10,000 interventions. Hypotension/hypoperfusion was the most frequently found preexisting condition (42.5%). The main cause was the presence of preoperative complications (57.5%). Nineteen cases (23.8%) were attributable to anesthesia, with an incidence of 1.11 per 10,000 anesthetic procedures. Survival rate at hospital discharge was 52.5%. The figure for PCA caused by anesthesia was 84.2%. CONCLUSIONS: The incidence of PCA and its survival is similar to that reported abroad. In general, PCA has a better prognosis than other types of cardiac arrest, especially if it has an anesthetic cause.

Registro de paro cardiorrespiratorio perioperatorio en un hospital universitario en el período 2006-2017 / Registry of perioperative cardiac arrests in a clinical hospital in the period 2006-2017

Background: Perioperative cardiac arrest (PCA) is a rare but important event in the operating room. Aim: To describe PCA events at a Clinical Hospital in Santiago, Chile. Material and Methods: Registry of PCA that occurred in the operating room (OR) and during procedures not carried out in the OR between September 2006 and November 2017. Precipitating events, type of anesthesia and results of resuscitation maneuvers were described. Results: Eighty events (five outside of the OR) during 170,431 surgical procedures were recorded, resulting in an incidence of 4.4 events per 10,000 interventions. Hypotension/hypoperfusion was the most frequently found preexisting condition (42.5%). The main cause was the presence of preoperative complications (57.5%). Nineteen cases (23.8%) were attributable to anesthesia, with an incidence of 1.11 per 10,000 anesthetic procedures. Survival rate at hospital discharge was 52.5%. The figure for PCA caused by anesthesia was 84.2%. Conclusions: The incidence of PCA and its survival is similar to that reported abroad. In general, PCA has a better prognosis than other types of cardiac arrest, especially if it has an anesthetic cause.

Mantenimiento del donante de órganos: recomendaciones generales que precisan evidencia / Organ donor management: Common recommendations that deserve evidence

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Leuprolide acetate gonadotrophin response patterns during female puberty.

OBJECTIVE: To assess normative data and the usefulness of spontaneous and LHRH analogue-stimulated serum LH and FSH levels measured by immunoradiometric assays (IRMA) in the evaluation of normal puberty. DESIGN: Prospective. Healthy girls in Tanner I and Tanner II from the local community were invited to participate (n = 47). METHODS: A leuprolide acetate test (500 mcg/m(2); sc) was performed. LH and FSH levels were determined using IRMA. Tanner II girls were assessed every 6 months until Tanner V. Girls who progressed from Tanner II to Tanner III in the next 6 months were called Tanner II-2; otherwise, they were called Tanner II-1. RESULTS: The prepubertal upper limit (CI 95%) was 0.49 IU/l for basal LH and 5.1 IU/l for stimulated LH. Taking into account these LH cut-off limits, 72.2% and 66.7% of Tanner II-1 and 41.6% and 41.7% of Tanner II-2 subjects presented overlapping values for basal and stimulated LH, respectively, as compared with the Tanner I group. The cut-offs for basal and stimulated LH to predict progression from Tanner II to Tanner III in the next 6 months were a basal LH level > or =0.49 IU/l (Sensitivity = 0.58; 1-Specificity = 0.33) and a poststimulated LH level > or =4.75 IU/l (Sensitivity = 0.67; 1-Specificity = 0.44). CONCLUSION: According to an IRMA, the basal and leuprolide acetate gonadotrophin response patterns during the beginning stages of puberty overlapped between Tanner I and Tanner II, and the cut-offs of basal and stimulated LH levels to predict progress from Tanner II to Tanner III had low sensitivities for the following 6 months.

Deficiencia somatotrófica en niños: características clínicas y bioquímicas según la etiología en 75 casos / Somatotrophic deficiency in children: report of 75 cases

Somatotrophic deficiency (SDMT) can be due to a deficiency of growth hormone releasing hormone(GHRH), growth hormone (GH) or insulin like growth factor I (IGF-I). Although its clinical features have been thoroughly described, the diagnosis is still controversial. Now there is an effective treatment with GH or IGF-I for these patients. AIM: To analyze the main clinical, etiological and laboratory characteristics of 75 SD patients (44 males), aged 9.4 + 4.5 years, with severe growth retardation. The diagnosis was confirmed by the lack of response to two GH stimulation tests (Clonidine, Glugagon or Insulin) and low levels of IGF-I or insulin-like growth factor binding protein- 3 (IGFBP-3). RESULTS: In 34 patients (46 percent), the cause of DSMT was considered idiopathic (DSMT-I), in 31 (41 percent) there was an organic cause (DSMT-O), most commonly caused by malformations or pituitary tumors and in 10 (13 percent), it was genetic (DSMT-G) (three patients with Laron's Syndrome, five with mutations of GH gene and 2 with probable mutations of Prop-1 and Pit-1 genes). IGF-1 levels, were significantly lower in DSMT-O and DSMT-G thanin DSMT-I (21.2 +/- 46.1, 23.4 +/-30.3 ng/mL and 50.2 +/- 48.3 ng/mL, respectively). The lowest height score corresponded to DSMT-G, compared to DSMT-O and DSMT (­5.7 +/- 0.9, -4.0 +/- 1.6 and ­4.3 +/- 1.2 DS, respectively) CONCLUSIONS: The high percentage of organic and genetic etiologies in our patients can be due to the systematic search of these diseases. DSMT-G (Laron, mutations in GH and Pit-1 genes) had the most severe growth retardation.

Comparison of leptin levels, body composition and insulin sensitivity and secretion by OGTT in healthy, early pubertal girls born at either appropriate- or small-for-gestational age.

BACKGROUND: Small for gestational age (SGA) has been associated with decreased insulin sensitivity (IS). A possible mechanism is the postnatal development of a metabolically disadvantageous body composition (BC). AIM: To determine whether there are differences between IS and BC in girls in early puberty who were SGA (birth weight < 10th percentile) or appropriate for gestational age (AGA, 10th-90th percentile). METHODS: Age-matched (SGA/AGA) early pubertal girls (Tanner II) were recruited from local schools. We determined waist circumference (WC), the sum of four skinfolds (S4S), and per cent fat mass (fat %) by impedanciometry. Leptin and OGTT assays were performed. The insulinogenic index (I-In), HOMA-IR (homeostasis model assessment of insulin resistance) and WBISI (whole body insulin sensitivity) were calculated. RESULTS: Median age (interquartile range) for 30 SGA and 35 AGA girls was 10.2 (1.1) vs. 9.8 (0.9), respectively (P = NS). BMI percentiles were 62.6 (56) vs. 67.4 (39); WC 60.5 (9.5) vs. 62.2 (6.5) cm; S4S 52 (30) vs. 52.2 (29.5) cm, and fat %[26.2 (6.7) vs. 28.5 (6.3)] was similar in both groups. SGA girls had higher leptin levels [15.4 (9.7) vs. 9.6 (11) ng/ml; P = 0.01] and I-In [2.05 (1.86) vs. 1.47 (1.27) microU/ml* mg/dl; P = 0.02]. No differences between HOMA-IR [2.07 (1.26) vs. 2.04 (1.4)] and WBISI [5.3 (3.3) vs. 5.1 (3.1)] were found between groups. CONCLUSION: The higher leptin level and I-In in girls born SGA at the beginning of puberty may be early indicators of an underlying subtle degree of insulin resistance, despite similar BMI and BC to AGA girls.

Comparison of clinical, ultrasonographic, and biochemical differences at the beginning of puberty in healthy girls born either small for gestational age or appropriate for gestational age: preliminary results.

CONTEXT: There are limited and controversial data concerning puberty characteristics in girls born small for gestational age (SGA). OBJECTIVE: The objective of the study was to document clinical, ultrasonographic, and biochemical characteristics at the beginning of puberty in matched healthy girls born either SGA or appropriate for gestational age (AGA) recruited from the community. PATIENTS: Inclusion criteria were breast Tanner stage II and a body mass index between the 10th and 95th percentiles. INTERVENTIONS: Recruited subjects underwent a complete physical exam, bone age, and ultrasound measurements of the internal genitalia. Hormonal assessment included fasting early morning dehydroepiandrosterone sulfate, androstenedione, SHBG, inhibin-B, FSH, LH, estradiol (E2), 17-hydroxyprogesterone (17OH Prog), and testosterone. Thereafter, a GnRH agonist test (leuprolide 500 microg, sc) was performed with FSH and LH at time 3 and 24 h for E2, 17OH Prog, and testosterone. RESULTS: Sixty-five girls (35 AGA, 30 SGA) with a mean age of 9.9 +/- 1.03 (7.8-12.5) yr, similar bone age/chronological age (1.02 +/- 0.8 in AGA and 1 +/- 0.76 in SGA), median height of 1.35 +/- 0.06 cm, and similar waist to hip ratio were included. No differences in the presence of pubic hair, axillary hair, apocrine odor, or ultrasound measurements were found. SGA girls had increased baseline E2 as well as stimulated E2 and 17OH Prog. CONCLUSIONS: In a preliminary sample of lean, healthy girls recruited from the community born either SGA or AGA, we observed slight hormonal differences at the beginning of puberty. Longitudinal follow-up of this cohort will allow us to understand whether these differences are maintained and have a clinical impact in their pubertal development.

Longitudinal changes in insulin sensitivity and secretion from birth to age three years in small- and appropriate-for-gestational-age children.

AIMS/HYPOTHESIS: Insulin resistance and type 2 diabetes risk in human subjects who were small-for-gestational-age (SGA) at birth may be a consequence of rapid early postnatal weight gain. MATERIALS AND METHODS: We prospectively studied early changes in fasting insulin sensitivity and insulin secretion, assessed by a short intravenous glucose tolerance test that was conducted several times from birth to 3 years of age in 55 SGA (birthweight below fifth percentile) newborns and in 13 newborns with a birthweight appropriate for gestational age (AGA). RESULTS: Most SGA infants showed postnatal upward weight centile crossing and by 3 years were similar in size to AGA infants. SGA infants had lower pre-feed insulin levels at postnatal age 48 h than AGA infants (median 34.4 vs 59.7 pmol/l, p<0.05), but by the age of 3 years they had higher fasting insulin levels (median 38.9 vs 23.8 pmol/l, p<0.005), which were related to rate of weight gain between 0 and 3 years (r=0.47, p=0.0003). First-phase insulin secretion did not differ between SGA and AGA infants, but SGA infants had a lower glucose disposition index (beta cell compensation) (median 235 vs 501 min mmol(-1) l(-1), p=0.02), which persisted after allowing for postnatal weight gain (p=0.009). CONCLUSIONS/INTERPRETATION: SGA infants showed a marked transition from lower pre-feed insulin and increased insulin sensitivity at birth to insulin resistance over the first 3 years of life. This transition was related to rapid postnatal weight gain, which could indicate a propensity to central fat deposition. The additional observation of reduced compensatory beta cell secretion underlines the need for long-term surveillance of glucose homeostasis in all SGA subjects, whether or not they show postnatal catch-up growth.

Thermodynamic compatibility of sodium caseinate with different pectins. Influence of the milieu conditions and pectin modifications.

Combinations of pectins and caseins are ingredients of many food products. Therefore the thermodynamic compatibility of both components was examined to investigate the influences of environmental factors as well as of the structure of the pectin. High-methoxyl pectin was demethoxylated and amidated, respectively, and tested for the compatibility with sodium caseinate under varying conditions of pH and ionic strength. The compatibility increased with increasing pH and decreasing ionic strength. Demethoxylated pectins were more and amidated pectins less compatible with the caseinate. Changes in the pectin hydrophilicity, solubility and molecular weight and possibly local interactions such as electrostatic attraction, hydrogen bonding and calcium bridges are involved in the compatibility of the components. The type and degree of the pectin modifications as well as the type, composition and properties of the protein were found to be of great importance for the thermodynamic compatibility.

Study of GH sensitivity in chilean patients with idiopathic short stature.

We hypothesized that some children with idiopathic short stature in Chile might bear heterozygous mutations of the GH receptor. We selected 26 patients (3 females, 23 males) from 112 patients who consulted for idiopathic short stature at the University of Chile. Their chronological age was 8.3 +/- 1.9, and bone age was 6.1 +/- 1.0 yr. Their height was -3.0 +/- 0.7 SDS; IGF-I, -1.2 +/- 1.1 SD; IGF binding protein 3, -0.7 +/- 2.0 SDS; and GH binding protein, 0.4 +/- 0.8 SDS. Patients were admitted, and blood samples were obtained every 20 min to determine GH concentrations overnight. Coding sequences and intron-exon boundaries of exons 2-10 of GH receptor gene were amplified by PCR and subsequently analyzed through single-strand conformational analysis. Mean serum GH concentration, over 12-h, was 0.20 +/- 0.08 nM; pulse amplitude, 0.40 +/- 0.15 nM; number of peaks, 5.8 +/-1.5 peaks/12 h; peak value of GH during the 12-h sampling, 1.03 +/- 0.53 nM; and area under the curve, 151.4 +/- 56.1 nM/12 h. There were positive correlations between mean GH vs. area under the curve (P < 0.001) and GH peak (P < 0.01). The single-strand conformational analysis of the GH receptor gene showed abnormal migration for exon 6 in 9 patients and for exon 10 in 9 patients, which (by sequence analysis) corresponded to 2 polymorphisms of the GH receptor gene: an A-to-G transition in third position of codon 168 in exon 6 and a C-to-A transversion in the first position of codon 526 in exon 10. We further sequenced all coding exons and intron-exon boundaries in the most affected patients (nos. 6, 9, 11, 14, 15, 16, and 23). This analysis revealed a C-to-T transition in codon 161 of exon 6 in patient 23, which results in an amino acid change (Arg to Cys) in an heterozygous form in the patient and his father. In conclusion, the results of our study suggest that, in Chilean patients with idiopathic short stature, GH receptor gene mutations are uncommon, although we cannot exclude mutations that were missed by single-strand conformational analysis or mutations within introns or in the promoter regions of the GH receptor gene.

[Reference values of growth hormone binding protein (GHBP) for a normal pediatric population]. / Valores de referencia para proteína transportadora de hormona de crecimiento en una población pediátrica normal.

UNLABELLED: Circulating concentrations of the high affinity growth hormone binding protein (GHBP) may be a marker of GH receptor density as well as GH sensitivity. GOAL: To determine values of GHBP for a normal Chilean pediatric population. METHODS: We determined GHBP levels in 73 males and 73 females between 4 to 15.5 years and 4 to 16.8 years respectively, divided in 7 groups according to age and puberal status. RESULTS: The population was normally distributed in weight, height and body mass index (BMI). GHBP activity increased up to Tanner IV in males and Tanner III in females, and decreased slightly thereafter in Tanner V and IV respectively. There was a significant difference between GHBP levels of preschool children and those found in Tanner II to V in both sexes (p < 0.05). In addition, we found a positive correlation between GHBP vs weight, height and BMI (p < 0.001) in males and females. CONCLUSION: The availability of this methodology allows us to establish the normative value of GHBP in our population and provides useful information to interpret GH circulating levels in children with growth disorders.

Relationship between serum growth hormone binding protein levels and height in young men.

The biochemical mediators responsible for variations in stature among normal subjects are largely unknown. To obtain some initial information about potential endocrine factors, we measured the serum concentrations of GH, IGF-1, IGFBP-3 and GHBP in healthy young men shorter than 159 cm and taller than 187 cm. We studied 14 volleyball and basketball players (tall group), and 14 jockey students from a horse racetrack (short group). A careful medical history was taken, including dietary intake, and physical examination with special attention to the possible presence of genetic stigmata was performed. Serum prealbumin was determined as an index of nutritional status. A buccal smear was performed to exclude Klinefelter's syndrome. The BMI and serum prealbumin levels were comparable in both groups of individuals. The nutritional survey, however, revealed that the tall subjects had a higher intake of calories (42.2+/-11.2 vs. 30.1+/-15.15 kcal/kg, p<0.05), and protein (1.5+/-0.6 vs. 0.8+/-0.4 mg/kg, p<0.01). Serum concentrations of GHBP did not differ in the two groups (0.95+/-0.37 nmol/l in the tall, and 0.95+/-0.53 nmol/l in the short group), and did not correlate with height, serum IGF-I levels, or BMI. We observed a significant difference in the serum concentrations of IGF-I in the two groups of individuals (42.02+/-9.37 nmol/l in the tall and 31.79+/-3.18 nmol/l in the short group, p<0.05), and this growth factor showed a positive correlation with height (r = 0.5, p<0.01). These preliminary findings suggest that final height differences in young men do not appear to be mediated by variations in GHBP concentrations.

Effect of patient information on the quality of pharmacists' drug use review decisions.

OBJECTIVE: To evaluate the effect of incremental increases in patient information on the quality of pharmacists' clinical decisions related to legally mandated prospective drug utilization review (DUR) responsibilities. DESIGN: Unblinded comparison of two groups. PARTICIPANTS: 28 community pharmacists in Indiana (group 1) and 32 Public Health Service pharmacists employed in the Indian Health Service (IHS) (group 2). INTERVENTIONS: Clinical cases involving prescribing problems were developed from patient charts. Each case contained four levels of increasing patient information: Level 1 included only information required for a legal prescription in Indiana; Level 2 added the patient's current medication profile, age, and allergies; Level 3 added the diagnosis or reason for use of the prescribed medication; and Level 4 added the physician's progress note. Pharmacists were asked to evaluate the prescribed drug therapy at each level of each case and complete a Dispensing Appropriateness Index (DAI) report, which included all prospective DUR criteria required by the Omnibus Budget Reconciliation Act of 1990. The quality of pharmacists' DUR decisions at each level of patient information was evaluated by comparing pharmacists' responses on the DAI reports with the consensus judgment of two clinical experts. RESULTS: The quality of both community and IHS pharmacists' DUR decisions improved significantly at each incremental level of patient information. CONCLUSION: Pharmacists in this study made better decisions when they had access to more complete patient information on which to base their decisions.

[Usefulness of the measurement of insulin-like growth factor (IGF-I) and IGF-1 binding protein-3 (IGFBP-3) for the diagnosis of growth hormone (GH) deficiency in children]. / Utilidad de la determinación del factor de crecimiento insulino-simil tipo I (IGF-I) y de su proteína ligante tipo 3 (IGFBP-3) en el diagnóstico de la deficiencia de hormona de crecimiento en niños.

BACKGROUND: The diagnosis of GH deficiency (GHD) is based upon the results of GH stimulation tests, which have several drawbacks. AIM: To evaluate the usefulness of IGF-1 and IGFBP-3 for the diagnosis of GHD in prepuberal children. MATERIAL AND METHODS: We measured IGF-I and IGFBP-3 in three group of subjects: I. GHD (n: 24), height < -2SD for age (Z score, average +/- SD: -4.2 +/- 1.2), growth velocity < p10 (3.4 +/- 1.0 cm/year) and peak GH level on two GH stimulation tests < 7 ng/ml (1.2 +/- 0.6 ng/ml); II. Short non-GHD (NGHD, n: 32), height of -2.7 +/- 0.9 SD for age, growth velocity < p 25 (3.9 +/- 1.2 cm/year), and peak GH level on two GH stimulation tests > 7 ng/ml (15.3 +/- 6.9 ng/ml), y III. Normal school children (n: 35) with normal heights (-0.17 +/- 0.12 SD) were studied as controls. RESULTS: IGF-1 and IGFBP-3 were significantly lower in GHD than in NGHD and controls (p < 0.001), and in NGHD than in C (p < 0.001). We defined the normal range of both proteins as +/- 2 SD of the mean of the control group. Using this criteria, IGF-I was low in 21/24 GHD, and in 12/32 NGHD. IGFBP-3 was low in 22/24 GHD, and in 6/32 NGHD. Only 1 GHD patient had both exams in the normal range, suggesting that he is probably NGHD. 4/32 of the NGHD and both exams below normal range, suggesting that they are probably GHD. CONCLUSIONS: IGF-1 and IGFBP-3 are important tools for the diagnosis of GHD.

Effects of eight months treatment with graded doses of a growth hormone (GH)-releasing peptide in GH-deficient children.

Stimulation of pituitary GH secretion with administered GHRH can be effective therapy for those GH deficient (GHD) patients whose disorder results from insufficient endogenous GHRH secretion. We have previously shown that most such patients also respond acutely to the GH-releasing peptides (GHRP's), which have a different mechanism of action from GHRH, with release of GH. In this study we tested whether the GH response to a newer GHRP, GHRP-2, would be sustained over time. Six prepubertal children with GHD and growth failure received stepwise increasing s.c. doses of GHRP-2, at 0.3, 1.0, and 3.0 micrograms/kg/day, in successive 2-month treatment periods, with monitoring of overnight 12 h episodic GH secretion and toxicity measures at the end of each period. During a fourth 2-month period, they received 3 micrograms/kg GHRP-2 together with 3 micrograms/kg s.c. GHRH. Serum levels of IGF-I and IGFBP-3 were also measured, and stadiometer height measurements were recorded. GHRP-2 administration produced a dosewise increase in overnight GH secretion. GH profiles showed that the effect of GHRP-2 injections was relatively brief, with little effect upon GH secretion later in the night. Serum levels of IGF-I and of IGFBP-3 did not increase. Growth velocity was higher during GHRP-2 treatment than during pretreatment and post-treatment evaluations. There were no side effects or toxicities observed. Thus GHRP-2 is well tolerated and is able to stimulate GH secretion. Formulations or routes of administration that allow for a longer duration of action will likely be needed to use GHRP-2 in therapy.

Effects of flunixin and mefenamic acid on cardiac pacemaker cells. Structure-activity relationship and comparison with clonixin.

1. The electrophysiological effects of flunixin and mefenamic acid, non-steroidal analgesics, on frog cardiac pacemaker cells, were studied by intracellular action potential recording. 2. Results show that flunixin (Flx) between 2 x 10(-6) and 1 x 10(-4) M, exerts a frequency, OS, APA and Vmax concentration-dependent decrease, similar to the effects of clonixin (Clx) reported elsewhere (Morales et al., Gen. Pharmac. 23, 515-521, 1992). 3. At 2.5 x 10(-4) M, Flx induces a complete cessation of the electrical activity of subsidiary pacemaker cells. 4. Mefenamic acid (Mef), in spite of its structural similarity with Clx and Flx, induces no appreciable electrophysiological changes. 5. Flx effects were partially reversed by increasing external calcium concentration and fully antagonized by BAY K-8644, a calcium L-type channel agonist. 6. By comparing the structures of the three fenamates studied, it is suggested that the nitrogen of the heterocycle and the electron-donor capacity of the bencenic ring are essential features for the calcium-antagonist activity of Clx and Flx.

Effects of clonixin on the electrical activity of cardiac pacemaker cells.

1. The electrophysiological effects of clonixin, a non-steroidal analgesic, on cardiac pacemaker cells of spontaneously beating frog sinus venosus, were studied by intracellular recording of transmembrane potentials. 2. Results show that clonixin (Clx) between 1 x 10(-6) M and 3 x 10(-4) M, decreases the OS, APA, Vmax and frequency of primary and subsidiary cells, however pacemaker cells differ in their sensitivity to Clx. 3. At 2 x 10(-6) M, Clx completely blocked the spontaneous beating of primary cells. It is necessary to increase the Clx concentration about two orders of magnitude in order to attain a similar degree of blockade of subsidiary cells. 4. Previous or simultaneous superfusion with atropine does not modify Clx effects, thus a probable cholinergic mechanism of action for Clx is discarded. 5. When Clx concentrations were lower than 5 x 10(-4) M, their effects on both types of cells were partially reversed by a 100% increase of external calcium concentration. 6. BAY K-8644 which stimulates calcium influx through calcium L-type channels, reverted Clx effects on pacemaker cells. 7. It is suggested that Clx blocks calcium inward current which generates all or part of the upstroke of primary cells and subsidiary ones, respectively.

Effect of surgical blood loss and volume replacement on antibiotic pharmacokinetics.

Antibiotic prophylaxis is used widely to prevent postoperative infection associated with cardiac operations. The influence of perioperative blood loss on antibiotic pharmacokinetics has not been well studied. Plasma cefazolin sodium samples from 8 patients undergoing a cardiac operation were collected postoperatively and analyzed. The results suggest that blood loss has a minimal effect on the elimination of cefazolin and that therapeutic concentrations are maintained without altering the dosage regimen.