Pulmonary distribution and efficacy of exogenous surfactant in lung-lavaged rabbits are influenced by the instillation technique

Surfactant bolus instillation has been reported to cause changes in arterial blood pressure (BP) and cerebral blood flow velocities which may increase the risk of intraventricular haemorrhage. To avoid these effects, slow tracheal infusion was evaluated as a possible alternative method of surfactant administration. Saline lung lavages were performed in 13 anesthetized and artificially ventilated adult rabbits to produce respiratory distress syndrome. Curosurf (CS, 200 mg/kg) labeled with 14C-dipalmitoyl-phosphatidylcholine (-DPPC) and/or red microspheres (RMS) was instilled into the trachea either as a single bolus (n = 8) or by infusion during 45 min via a side-channel within the wall of the tracheal tube (n = 5). An arterial cannula was placed for monitoring of blood gases and BP. To determine surfactant distribution, the lungs were cut into 60-70 pieces and radioactivity and/or the number of RMS were measured in each piece. The distribution of RMS was closely related to the distribution of 14C-DPPC (r = 0.96). Bolus instillation of CS led to a prompt and sustained increase in PaO2 (from < 10.5 to > 40 kPa within 2 min), a transient decrease in BP, and a reasonably homogeneous pulmonary surfactant distribution. Tracheal infusion of CS changed neither BP nor PaO2 during the observation period of 60 min. The pulmonary distribution of CS was extremely uneven after infusion. The distribution of exogenous surfactant and its effects on gas exchange are influenced by the instillation method. An inadequate instillation technique may add to the causes of "poor response" after surfactant replacement.     

Hippocampectomy disrupts trace eye-blink conditioning in rabbits.

The role of the hippocampus (HPC) in trace eye-blink conditioning was evaluated using a 100-ms tone conditioned stimulus/stimuli (CS), a 300- or 500-ms trace interval, and a 150-ms air puff unconditioned stimulus/stimuli (UCS). Rabbits received complete hippocampectomy (dorsal & ventral), sham lesions or neocortical lesions. Hippocampectomy produced differential effects in relation to the trace interval used. With a 300-ms trace interval, HPC-lesioned Ss showed profound resistance to extinction after acquisition. With a 500-ms trace interval, HPC-lesioned Ss did not learn the task (only 22% conditioned responses [CRs] after 25 sessions, whereas controls showed >80% after 10 sessions), and on the few trials in which a CR occurred, most were "nonadaptive" short-latency CRs (i.e., they started during or just after the CS and always terminated prior to UCS onset). The authors conclude that the HPC encodes a temporal relationship between CS and UCS, and when the trace interval is long enough (e.g., 500 ms), that the HPC is necessary for associative learning of the conditioned eye-blink response. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

In vivo morphometry of the intrasulcal gray matter in the human cingulate, paracingulate, and superior-rostral sulci: hemispheric asymmetries, gender differences and probability maps

Volumes of the intrasulcal gray matter were measured in three cerebral sulci located on the medial wall of the human frontal lobe: cingulate sulcus (CS), paracingulate sulcus (PCS), and superior-rostral sulcus (SRS). The measurements were carried out on T1-weighted 3-D high-resolution magnetic-resonance (MR) images acquired in 105 young right-handed volunteers (42 female and 63 male). Before the measurement, the images were transformed into a standardized stereotaxic space (Talairach and Tournoux [1988] Human Brain: 3-Dimensional Proportional System. An Approach to Cerebral Imaging. Stuttgart, New York: Georg Thieme Verlag), thus removing inter-individual differences in brain size. The intrasulcal gray matter was segmented in a semi-automatic manner. Significant gender differences were found in the volume of the CS (female > male) and the PCS (male > female). Hemispheric asymmetries were observed between the left and right volumes of the intrasulcal gray matter in the anterior (right > left) and posterior (left > right) segments of the CS, as well as between the left and right volumes of the PCS (left > right). There was no interaction between the asymmetries and gender. In addition, significant positive correlations were found between the left and right gray-matter volumes in the anterior (r = 0.43) and posterior (r = 0.66) segments of the CS, whereas significant negative correlations were observed between the gray-matter volumes of the anterior segment of the CS and those of the PCS (left hemisphere: r = -0.48; right hemisphere: r = -0.42). The observed hemispheric asymmetries in the CS and PCS gray-matter volumes are consistent with the proposed role of these structures in the integration of emotions with cognition (CS) and in the control of speech/vocalization (PCS). The pattern of inter-hemispheric correlations in the sulcal gray-matter points to an increasing asynchrony in the foetal development of primary (CS), secondary (SRS), and tertiary (PCS) sulci, respectively. The presence of negative correlations between the two neighbouring sulci (CS and PCS) suggests that a process of compensation could underlie interactions between adjacent primary and tertiary sulci. Besides the above volumetric analysis, we also provide average (probability) maps of the three sulci; the use of such maps for the parcellation of the medial frontal lobe and localization of "peaks" obtained in blood-flow activation studies is discussed.     

Cholic acid sorption by food fibers

We studied anticoagulant effects of combined administration of heparin (H) and chitosan sulfate ether (CS) (specific activity 20 UE/mg) in the ratio 1 : 1. CS enhanced anticoagulant activity of heparin in rabbits by a factor of 1.95 +/- 0.15. The intravenous injection of the mixture in a dose of 0.5 mg(H)/kg + 0.5 mg(CS)/kg and heparin injection in a dose of 1mg/kg induced the same effect. Haemorrhagic effect of this mixture was less pronounced compared to heparin, anticoagulant and antithrombotic activities remained the same. The mixture was found to decrease a number of platelets, however, this was also less pronounced compared to heparin. Thus, the use of the mixture CS + H (1 : 1) instead of double heparin dose resulted in the same effect.     

Triple dose of gadolinium-DTPA and delayed MRI in patients with benign multiple sclerosis

OBJECTIVES: To evaluate whether a triple dose of gadolinium-DTPA (Gd-DTPA) or delayed MRI increase the number, size, and conspicuousness of enhancing lesions in patients with benign multiple sclerosis. METHODS: T1 weighted brain MRI was carried out on 20 patients with benign multiple sclerosis (expanded disability status scale < 3 with a disease duration > 10 years) in two sessions. In the first session, one scan was obtained before and two scans five to seven minutes and 20-30 minutes after the injection of 0.1 mmol/kg Gd-DTPA (standard dose). In the second session, six to 24 hours later, the same procedure was repeated with 0.3 mmol/kg Gd-DTPA (triple dose). RESULTS: Nine enhancing lesions were found in seven patients (35%) using the standard dose of Gd-DTPA. The numbers of enhancing lesions increased to 13 (P = 0.03) and the number of patients with such lesions to eight (40%) on the delayed standard dose scans. On the early triple dose scans, we found 19 enhancing lesions in 10 patients (50%). The number of enhancing lesions was significantly higher (P = 0.01) than that obtained with the early standard dose. The number of enhancing lesions was 18 and the number of "active" patients 11 (55%) on the delayed triple dose scans. The enhancing areas increased progressively from the early standard dose scans to the delayed triple dose scans. The contrast ratios of the lesions detected in early standard dose scans was lower than those of lesions present in the early (P = 0.01) and delayed (P = 0.04) triple dose scans. CONCLUSIONS: More enhancing lesions were detected in patients with benign multiple sclerosis with both delay of MRI and the use of triple dose of Gd-DTPA suggesting that the amount of inflammation in the lesions of such patients is mild and heterogeneous.     

CS and UCS intervals and orders in human autonomic classical differential trace conditioning.

[Correction Notice: An erratum for this article was reported in Vol 25(3) of Canadian Journal of Psychology Revue Canadienne de Psychologie (see record 2007-04520-001). In diagram appearing in this erratum should be substituted for the diagram appearing as Figure 2 on p. 423 of the article.] Measured the GSR and digital volume-pulse change in 4 groups of 80 Ss each with light and tone as CS and shock as UCS. For Groups I and II, the CS-UCS interval was .75 and 7.5 sec., respectively; for Groups III and IV, the UCS-CS interval was .75 and 7.5 sec., respectively. Group III showed "backward" differential conditioning in the GSR; Group II yielded reliable conditioning of "multiple responses" occurring before UCS onset; the magnitude and extent of conditioning was greater in Group I than in Groups II and III, which did not differ; some evidence for "reverse" conditioning was suggested in Group IV, with slightly greater responding to the CS not paired with the UCS; instructions which distracted 1/2 the Ss from the CS did not affect responding to those stimuli. (French summary) (16 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

"CS and UCS intervals and orders in human autonomic classical differential trace conditioning": Erratum.

Reports an error in "CS and UCS intervals and orders in human autonomic classical differential trace conditioning" by John J. Furedy (Canadian Journal of Psychology Revue Canadienne de Psychologie, 1970[Dec], Vol 24[6], 417-426). The diagram appearing in this erratum should be substituted for the diagram appearing as Figure 2 on p. 423 of the article. (The following abstract of the original article appeared in record 1971-24206-001.) Measured the GSR and digital volume-pulse change in 4 groups of 80 Ss each with light and tone as CS and shock as UCS. For Groups I and II, the CS-UCS interval was .75 and 7.5 sec., respectively; for Groups III and IV, the UCS-CS interval was .75 and 7.5 sec., respectively. Group III showed 'backward' differential conditioning in the GSR; Group II yielded reliable conditioning of 'multiple responses' occurring before UCS onset; the magnitude and extent of conditioning was greater in Group I than in Groups II and III, which did not differ; some evidence for 'reverse' conditioning was suggested in Group IV, with slightly greater responding to the CS not paired with the UCS; instructions which distracted 1/2 the Ss from the CS did not affect responding to those stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pathology of arrhythmogenic right ventricular cardiomyopathy/dysplasia--an autopsy study of 20 forensic cases

The effects of postpartum energy intake, restricted suckling, and cow-calf isolation on concentrations of LH, FSH, growth hormone, and insulin-like growth factor-I (IGF-I) and on postpartum anestrous interval were determined by randomly allocating beef cows with a mean body condition score of 2.3 +/- 0.1 to receive either 80 MJ metabolizable energy (low-energy diet [L]; n = 51) or 120 MJ metabolizable energy (high-energy diet [H]; n = 52) per cow per day from calving. At 30 days postpartum, cows within diet were randomized to 1) have continued full access to their calves from birth to weaning (ad libitum suckling: ADLIB), 2) be suckled once-daily with their calves penned adjacent (restricted suckling, adjacent: RESADJ), 3) be isolated from all calves except for a once-daily suckling period (restricted suckling, isolated: RESISO). The mean postpartum interval was similar (p > 0.10) for L and H cows (62 and 63 days, respectively). RESADJ cows had a shorter (p < 0.05) postpartum interval than ADLIB cows, and RESISO cows had a shorter interval (p < 0.05) than RESADJ cows, with all effects independent (p > 0.10) of diet. FSH secretion pattern was not affected by diet, suckling treatment, sequential follicle wave number, or follicle wave retrospectively realigned to emergence of first ovulatory wave. Within 5 days of suckling restriction and calf isolation, the number of LH pulses increased from 0.18 to 0.48 pulses per hour (p < 0.05). Both mean LH and the mean number of LH pulses increased linearly (p < 0.01) during the six follicle waves up to the first ovulatory wave. From 80 days before, until the time of, first ovulation, growth hormone decreased (p < 0.05) while IGF-I increased (p < 0.05), irrespective of treatment. The results indicate that the "suckling effect" in beef cows is the major factor affecting the duration of the postpartum interval and suggests that the maternal bond is more important than suckling in regulating LH pulse frequency, the key endocrine factor determining whether or not a dominant follicles ovulates. Removal of the suckling effect resulted in a rapid increase in LH pulse frequency, which was not dependent on level of postpartum nutrition, at least within the nutritional limits of this study. Mean concentrations of FSH, unlike LH, did not vary with follicle wave number, suggesting that lack of FSH is not a major factor delaying the resumption of ovulation in postpartum beef cows.     

Thyroid cancer rates and 131I doses from Nevada atmospheric nuclear bomb tests

BACKGROUND: We examined data on death from thyroid cancer across the continental United States and data on incidence from selected areas of the country for evidence of an association between this disease and exposure to radioactive iodine (131I) from nuclear tests in Nevada in the 1950s. METHODS: Analyses involving 4602 thyroid cancer deaths (1957-1994) and 12 657 incident cases of thyroid cancer (1973-1994) were performed. Excess relative risks (ERRs) per Gray (Gy) of radiation were estimated by relating age-, calendar year-, sex-, and county-specific rates to estimates of dose to the thyroid that take age at exposure into account. RESULTS: Analyses of cumulative dose yielded negative ERRs that were not statistically significant. An association was suggested for dose received by children under 1 year of age for both mortality data (ERR per Gy = 10.6; 95% confidence interval [CI] = -1.1 to 29) and incidence data (ERR per Gy = 2.4; 95% CI = -0.5 to 5.6); no association was found for dose received at older ages. For mortality data, but not incidence data, there was an elevated ERR in the 1950-1959 birth cohort of 12.0 (95% CI = 2.8 to 31) per Gy. CONCLUSIONS: Risk of thyroid cancer from exposure to 131I from atmospheric nuclear tests did not increase with cumulative dose or dose received at ages 1-15 years, but associations were suggested for individuals exposed under 1 year of age and for those in the 1950-1959 birth cohort. The absence of increased risk from dose received at ages 1-15 years is not consistent with studies of children exposed to external radiation sources. This inconsistency may result from the limitations and biases inherent in ecologic studies, including the error introduced when studying a mobile population. These problems preclude making a quantitative estimate of risk due to exposure; however, given such limitations, it is perhaps remarkable that any evidence of the effects of 131I emerges from this study.     

Real-time processing of serial stimuli in classical conditioning of the rabbit's nictitating membrane response.

Real-time models contend that a CS gives rise to a cascade of hypothetical stimuli that govern CRs on a moment-to-moment basis. Experiments with the rabbit nictitating membrane response successfully extended these models to external stimuli. CRs were trained in sequence with an unconditioned stimulus/stimuli (UCS) (CSA–CSB–UCS). When the CSA–CSB interval was shortened, the CR was compressed; when the CSA–CSB interval was lengthened, the CR was broadened. Peaks appeared at 2 places, namely, one following CSA by a period equal to the CS–UCS interval and another following CSB by its CS–UCS interval. Outside the sequence, the individual CSs evoked CRs located between their respective CS–UCS intervals. When, however, the 2 CSs were trained separately, the CRs were appropriate to their respective CS–UCS intervals when tested alone or in sequence. The results are discussed in terms of the J. E. Desmond and J. W. Moore (1988) and S. Grossberg and N. A. Schmajuk (1989) models. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Adverse outcomes of antiinflammatory therapy among patients with polymyalgia rheumatica

OBJECTIVE: To evaluate the incidence and risks of adverse events associated with therapy (both corticosteroids [CS] and nonsteroidal antiinflammatory drugs [NSAIDs]) among a previously identified, population-based cohort of patients first diagnosed with polymyalgia rheumatica (PMR) between 1970 and 1991 who were followed up over the long term. METHODS: Information on demographics, PMR diagnosis, disease course, and drug therapy, in addition to data on adverse events commonly associated with CS and NSAID treatment, was obtained from the Rochester Epidemiology Project database. Cox proportional hazards and regression analysis models were used to evaluate the relationship between the occurrence of these events and therapy. RESULTS: Of the 232 patients (69 male, 163 female) included in the study, the mean age at PMR diagnosis was 72.9 years, the average followup was 8.0 years, and 30 patients were also diagnosed with giant cell (temporal) arteritis. Among the 175 patients (49 male, 126 female) treated with CS, the mean duration of CS therapy was 2.4 years, the average daily dose was 9.6 mg, and the mean cumulative dose was 8.4 gm. In total, 65% of the 124 patients treated with CS alone experienced at least 1 adverse event, compared with 67% of the 57 patients treated with NSAIDs alone and 80% of the 51 patients treated with CS and NSAIDs. The average time from initiation of therapy to the first adverse event was 1.6 years (n = 160). Proportional hazards modeling identified 3 variables that independently increased the risk of adverse events: age at PMR diagnosis, a cumulative dose of prednisone > or = 1,800 mg, and female sex. Person-year analysis revealed that the risks of diabetes mellitus, vertebral fractures, femoral neck fractures, and hip fractures were 2-5 times greater among PMR patients compared with age- and sex-matched individuals from the same population. Medical care or consultation by a rheumatologist was a highly significant predictor of a lower initial CS dose. CONCLUSION: The use of CS and NSAIDs in the treatment of PMR is associated with important long-term morbidity.     

Control of heart rate during transition from intravenous to oral diltiazem in atrial fibrillation or flutter

We tested whether patients presenting with atrial fibrillation (AF) or flutter (AFl) with a rapid ventricular response could maintain control of heart rate while transferring from a bolus and continuous infusion of intravenous diltiazem to oral diltiazem. Forty patients with AF or AFI and sustained ventricular rate > or = 120 beats/min received intravenous diltiazem "bolus" (20 to 25 mg for 2 minutes) and "infusion" (5 to 15 mg/hour for 6 to 20 hours). Oral long-acting diltiazem (diltiazem CD 180, 300, or 360 mg/24 hours) was administered in patients in whom stable heart rate control was attained during constant infusion. Intravenous diltiazem infusion was discontinued 4 hours after the first oral dose, and patients were monitored during 48 subsequent hours of "transition" to oral therapy. Response to diltiazem was defined as heart rate <100 beats/min, > or = 20% decrease in heart rate from baseline, or conversion to sinus rhythm. Other rate control or antiarrhythmic medications were not allowed during the study period. Thirty-seven of 40 patients maintained heart rate control during the bolus, and 35 of the remaining 37 maintained control during the infusion of intravenous diltiazem. Of the 35 patients achieving heart rate control with intravenous diltiazem who entered the transition to oral therapy, 27 maintained heart rate control (response rate of 77%/, 95% confidence interval 63% to 91%). The median infusion rate of intravenous diltiazem was 10 mg/hour, and the median dose of oral diltiazem CD was 300 mg/day. Oral long-acting diltiazem was 77% effective in controlling ventricular response over 48 hours in patients with AF or AFl in whom ventricular response was initially controlled with intravenous diltiazem.     

Response rate and reinforcement rate in Pavlovian conditioning.

Four experiments used delay conditioning of magazine approach in rats to investigate the relationship between the rate of responding, R, to a conditioned stimulus (CS) and the rate, r, at which the CS is reinforced with the unconditioned stimulus (US). Rats were concurrently trained with four variable-duration CSs with different rs, either as a result of differences in the mean CS-US interval or in the proportion of CS presentations that ended with the US. In each case, R was systematically related to r, and the relationship was very accurately characterized by a hyperbolic function, R = Ar/(r +c). Accordingly, the reciprocal of these two variables—response interval, I (= 1/R), and CS-US interval, i (= 1/r) – were related by a simple affine (straight line) transformation, I = mi+b. This latter relationship shows that each increment in the time that the rats had to wait for food produced a linear increment in the time they waited between magazine entries. We discuss the close agreement between our findings and the Matching Law (Herrnstein, 1970) and consider their implications for both associative theories (e.g., Rescorla & Wagner, 1972) and nonassociative theories (Gallistel & Gibbon, 2000) of conditioning. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Serum matrix metalloproteinase-9:Tissue inhibitor of metalloproteinase-1 ratio correlates with steroid responsiveness in moderate to severe asthma

Asthma presents a variable clinical response to corticosteroids (CS). Because CS more likely act on inflammation than on tissue remodeling, the presence of bronchial structural changes in certain asthmatics may explain their limited clinical response to CS. Matrix metalloproteinase-9 (MMP-9) and its inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), are, respectively, involved in tissue inflammatory processes and fibrogenic processes. Previous reports have suggested that MMP-9:TIMP-1 ratio may reflect the balance between these two processes in various diseases. This study evaluated the relation of this ratio and the response to CS in severe asthma. Twenty asthmatics with low baseline FEV1 (59 +/- 4% predicted) and >/= 30 % increase with beta2-agonist were recruited. Serum MMP-9 and TIMP-1 levels were measured and correlated with response to an oral CS trial (methylprenisolone 40 mg/d for 14 d). With oral CS, FEV1 changes (DeltaFEV1) ranged from -15 to +43%. The DeltaFEV1 closely correlated with the MMP-9:TIMP-1 ratios (rho = 0. 79, p = 0.0006). In conclusion, serum MMP-9: TIMP-1 ratio could predict the response of oral CS therapy in asthma. The low MMP-9:TIMP-1 ratio observed in subjects with little or no FEV1 improvement with CS supports the hypothesis that, in these asthmatic subjects, bronchial fibrogenesis predominates over inflammation.     

Structures of the van der Waals Isomers of Halosulfuric Acids: Microwave Spectra of HX-SO3 (X = F, Cl, Br)

The effects of different doses of filgrastim on yields of CD34+ peripheral blood stem cells were evaluated in patients with breast cancer. 55 were randomized to receive filgrastim 10, 20, 30 or 40 microg/kg/d with more CD34+ cells/kg/apheresis harvested after the three highest dose levels. 35 additional patients were randomized to receive 10 or 30 microg/ kg. The median number of CD34+ cells collected after 10 microg/ kg (n = 31) was 0.7 x 10(6)/kg/apheresis (range 0.1-4.4) as compared to 1.2 (range 0.1-6.8) after 30 microg/kg (n = 32) (P = 0.04). Among patients randomized to 10 v 30 microg/kg, more (50%) achieved > or = 5.0 x 10(6) CD34+ cells/kg and less aphereses were required to achieve > or = 2.5 x 10(6) CD34+ cells/kg after the higher dose (P = 0.04). In multivariate analyses, patients receiving 10 microg/kg (n = 31) had lower yields of CD34+ cells (P = 0.026) and had a 3.3-fold increase in the probability of not achieving > or = 5.0 x 10(6) CD34+ cells/kg as compared to patients receiving 20-40 microg/kg (n = 59). Patients who had received radiation had a 2.9-fold probability of not achieving > or = 2.5 x 10(6) CD34+ cells/kg. These data suggest that, in patients with good marrow reserves, doses of filgrastim > 10 microg/kg/d mobilized more CD34+ cells and may be useful when high numbers of CD34+ cells are desired.     

Significance of myocardial ischemic electrocardiographic changes during dipyridamole stress echocardiography

The aim of this study was to assess the diagnostic and prognostic value of the presence and characteristics of ischemic electrocardiographic (ECG) changes during dipyridamole stress echocardiography. The ECG response in 178 patients with echocardiographic evidence of myocardial ischemia during dipyridamole stress testing was analyzed. ECG changes occurred in 105 patients (59%). Patients with ECG changes had a higher incidence of echocardiographic signs of ischemia at a low dose than patients with an unchanged electrocardiogram (50% vs 23%; p = 0.0002). Three-vessel and/or left main coronary artery disease (CAD) was found in 41% of patients with and in 21% of patients without ECG changes (p = 0.029). During follow-up (33 +/- 19 months), 30 cardiac events occurred: 10 deaths, 6 infarctions, and 14 unstable anginas. Coronary revascularization was performed in 48 patients with and in 17 patients without ECG changes (p = 0.0022). The univariate predictors of cardiac events were: presence of ischemia in > or =4 ECG leads (p = 0.0004), echocardiographic evidence of ischemia at a low dose (p = 0.0062), ST-segment shift on precordial leads (p = 0.0094), family history of CAD (p = 0.0115), coexistence of > or =3 cardiovascular risk factors (p = 0.0156), ST-segment depression (p = 0.0172), and ECG changes during testing (p = 0.0335). At Cox analysis, occurrence of ischemia at a low dose (odds ratio 3.0; 95% confidence interval 1.3 to 6.8) and the presence of ischemia in > or =4 ECG leads (odds ratio 3.5; 95% confidence interval 1.3 to 9.3) had an independent prognostic importance. In conclusion, the presence and characteristics of ischemic ECG changes are associated with more extensive CAD and worse prognostic outlook than are echocardiographic changes alone during dipyridamole stress echocardiography.     

Limited-sampling strategy models for itraconazole and hydroxy-itraconazole based on data from a bioequivalence study

We assessed the sedative potential of continuous infusions of remifentanil with a validated composite alertness scale in 160 patients (ASA physical status I or II) undergoing hip replacement surgery with spinal block (n = 61) or hand surgery using brachial plexus block (n = 93). They were randomized to receive one of the following initial dose regimens in double-blinded fashion: placebo or 0.04, 0.07, or 0.1 microg x kg(-1) x min(-1) remifentanil subsequently titrated to effect. Additional midazolam IV was allowed for adequate sedation as required. The combined analysis of both surgery groups revealed a dose-related increase in achievement of sedation level > or =2 within 15 min of the start of the study drug infusion; all remifentanil dose comparisons with placebo reached significance (P < 0.001). The remifentanil 50% effective dose for a composite sedation level > or =2 within 15 min of the start of drug infusion was estimated as 0.043 microg x kg(-1) x min(-1) (95% confidence interval 0.01, 0.059). The requirement for midazolam decreased with increasing remifentanil dose compared with placebo (P < 0.001). The median time to return to alertness after the end of infusion was 10-12 min in the remifentanil groups and 5 min in the placebo group. Significant incidences of nausea, pruritus, sweating, and respiratory depression were reported during remifentanil infusions compared with placebo. The data suggest that remifentanil may be useful for supplementation of regional anesthesia, provided that ventilation is carefully monitored. IMPLICATIONS: In this dose-finding, placebo-controlled study, remifentanil infusions were used to provide sedation during spinal and brachial plexus regional anesthesia. The 50% effective dose for achievement of sedation was 0.043 microg x kg(-1) x min(-1). Return to alertness occurred after 10-12 min (median time). Remifentanil infusions can be used to supplement regional anesthesia, but this requires careful monitoring of ventilation.     

A transcript map of an 800-kb region on human chromosome 11q13, part of the candidate region for SCA5 and BBS1

OBJECTIVE: To evaluate whether small iodine supplements decrease the incidence of adolescent thyroid hypertrophy in an iodine-sufficient population or whether such thyroid enlargement should be considered an inevitable physiological phenomenon. DESIGN: Beginning in September 1991 (after an initial examination in September 1990), 54 11-year-old children in Bardejov, Slovakia were given small iodine supplements (Thyrojod depot tablets containing 1530 microg iodide) every 2 weeks for 2 years followed by once weekly for 2 years. A second group of 63 children served as controls. In June 1995, there were still 52 treated and 60 control children in the study and these were examined; 44 treated and 48 control children remained in the study until June 1997. METHODS: In 1990, 1993, 1995, 1996 and 1997 the thyroid volume (ThV) was measured by ultrasound. Serum levels of TSH, thyroglobulin, total and free thyroxine and tri-iodothyronine and anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-TG) and anti-TSH receptor (TSR) antibodies were estimated in 1990 and 1994, while only TSH, and anti-TPO and anti-TSR antibodies were measured in 1997. RESULTS: There was no difference between the groups at any interval in the serum levels of the hormones measured. Marginally increased TSH was found in two treated and two control children. Anti-TSR antibodies were negative in all children, while anti-TPO and anti-TG antibodies were found in one treated and four control children. At the age of 10 years (1990), 84% of all ThVs were less than 4 ml, indicating a previous life-long sufficient iodine intake. After the treatment was completed (June 1995), a significant difference in ThV (P < 0.04) was found between the whole treated (5.78 +/- 0.19 ml) and the whole control group (6.56 +/- 0.30 ml). However, there was already a marked difference in the 75th percentile (6.4 ml in treated vs 8.5 ml in controls) due to more rapid thyroid growth in certain children of the control group (ThV > 7.0 ml in 6/52 treated children vs 24/60 controls; P < 0.01). Since such differences were much higher in 1997, the children in each group whose ThV was in the range of the upper 25% in 1997 were retrospectively evaluated as arbitrary separate subgroups in all the time intervals and compared with the remaining 75% of children who showed moderate thyroid growth rate. Two years after the termination of treatment (June 1997), excessive thyroid growth continued in the upper quarter of 12 controls with the highest ThV (13.60 +/- 0.40 ml or 7.60 +/- 0.29 ml/m2; 12/12 with ThV > 11.0 ml), and a similar subgroup now also appeared in 11 previously treated children (10.79 +/- 0.51 ml or 6.19 +/- 0.30 ml/m2; 5/11 with ThV > 11.0 ml). At the same time, ThV in the remaining 75% of both control (8.12 +/- 0.38 ml or 4.82 +/- 0.17 ml/m2; 3/36 with ThV > 11.0 ml) and treated (7.20 +/- 0.30 ml or 4.39 +/- 0.17 ml/m2; 0/33 with ThV > 11.0 ml) children was significantly less (P < 0.01 to P < 0.001) than that in the appropriate rapidly growing subgroups. During the whole observation period (1990-1997), no difference was found between treated and control subgroups with moderate thyroid growth. CONCLUSIONS: Since iodine intake in Slovakia has been adequate for decades and sporadic iodine deficiency is highly unlikely, the observed excessive thyroid growth in certain adolescents may result from causes other than simple iodine deficiency (e.g. hereditary), which are nevertheless ameliorated by small iodine supplements. The question remains whether such a subgroup with rapidly growing thyroids should be included in the range of normal thyroid volumes in adolescents.     

Identification of anovulation and transient luteal function using a urinary pregnanediol-3-glucuronide ratio algorithm

The sensitivity and specificity of a urinary pregnanediol-3-glucuronide (PdG) ratio algorithm to identify anovulatory cycles was studied prospectively in two independent populations of women. Urinary hormone data from the first group was used to develop the algorithm, and data from the second group was used for its validation. PdG ratios were calculated by a cycles method in which daily PdG concentrations indexed by creatinine (CR) from cycle day 11 onward were divided by a baseline PdG (average PdG/Cr concentration for cycle days 6-10). In the interval method, daily PdG/CR concentrations from day 1 onward were divided by baseline PdG (lowest 5-day average of PdG/CR values throughout the collection period). Evaluation of the first study population (n = 6) resulted in cycles with PdG ratios > or = 3 for > or = 3 consecutive days being classified as ovulatory; otherwise they were anovulatory. The sensitivity and specificity of the PdG ratio algorithm to identify anovulatory cycles in the second population were 75% and 89.5%, respectively, for all cycles (n = 88); 50% and 88.3% for first cycles (n = 40) using the cycles method; 75% and 92.2%, respectively, for all cycles (n = 89); and 50% and 94.1% for first cycles (n = 40) using the interval method. The "gold standard" for anovulation was weekly serum samples < or = 2 ng/ml progesterone. The sensitivity values for all cycles and for the first cycle using both methods were underestimated because of apparent misclassification of cycles using serum progesterone due to infrequent blood collection. Blood collection more than once a week would have greatly improved the sensitivity and modestly improved the specificity of the algorithm. The PdG ratio algorithm provides an efficient approach for screening urine samples collected in epidemiologic studies of reproductive health in women.     

In vitro activities of oral beta-lactams at concentrations achieved in humans against penicillin-susceptible and -resistant pneumococci and potential to select resistance

The beta-lactam susceptibilities of 65 strains of Streptococcus pneumoniae for which penicillin MICs covered a broad range were assessed. The order of potency was amoxicillin (AMX) = amoxicillin-clavulanate (AMC) > penicillin G > cefpodoxime (CPO) > cefuroxime (CXM) > cefprozil > cefaclor > loracarbef > cefixime. No decrease in susceptibility was seen following repeated subculture of two penicillin-susceptible strains of S. pneumoniae in AMX, AMC, cefaclor, or loracarbef, whereas repeated exposure to CPO and CXM resulted in 4- to 32-fold decreases in susceptibility for both strains. When one of these strains was exposed to concentrations of CPO, CXM, AMX, and AMC achieved in the serum of humans following the administration of an oral dose, all agents were rapidly bactericidal, with no decrease in susceptibility up to 72 h. This was consistent with antibiotic concentrations exceeding the MICs for 100% of the dosing interval. For a penicillin-resistant strain, MICs were exceeded for 29% of the 12-h dosing interval for 500 mg of AMX, 42% of the interval for AMC with 875 mg of AMX and 125 mg of clavulanate (875/125 mg of AMC) 21% of the interval for 500 mg of CXM, and 0% of the interval for 200 mg of CPO. Consequently, only 875/125 mg of AMC produced a sustained bactericidal effect. A four- to eightfold reduction in susceptibility to CPO and CXM and cross-resistance with cefotaxime, but not penicillin or AMC, were selected following exposure to simulated serum CPO and CXM concentrations. In addition, AMX and AMC were the only agents which consistently produced a >99% reduction in bacterial numbers in time-kill studies using concentrations of antibiotic achieved in middle ear fluid for all three strains of penicillin-resistant S. pneumoniae tested.