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PubMed2004

Effects of different artificial insemination techniques and sperm doses on fertility of normal mares and mares with abnormal reproductive history.

The effects of different artificial insemination (AI) techniques and sperm doses on pregnancy rates of normal Hanoverian breed mares and mares with a history of barrenness or pregnancy failure using fresh or frozen-thawed sperm were investigated. The material included 187 normal mares (148 foaling and 39 young maiden mares) and 85 problem mares with abnormal reproductive history. Mares were randomly allotted into groups with respect to AI technique (routine AI into the uterine body, transrectally controlled deep intracornual AI ipsilateral to the preovulatory follicle, or hysteroscopic AI onto the uterotubal junction ipsilateral to the preovulatory follicle), storage method of semen (fresh, frozen-thawed), AI volume (0.5, 2, 12 ml), and sperm dose (50 x 10(6) or 300 x 10(6) progressively motile sperm (pms) for fresh semen and 100 or 800 x 10(6) frozen-thawed sperm with >35% post-thaw motility). The mares were inseminated once per cycle, 24 h after hCG administration when fresh semen was used, or 30 h for frozen-thawed semen. Differences in pregnancy rates between treatment groups were analyzed by Chi-squared test, and for most relevant factors (insemination technique, mare, semen, and stallion) expectation values and confidence intervals were calculated using multivariate logistic models. Neither insemination technique, volume, sperm dose, nor mare or stallion had significant effects (P > 0.05) on fertility. Type of semen, breeding mares during foal heat, and an interaction between insemination technique, semen parameters, and mares did have significant effects (P < 0.05). In problem mares, frozen semen AI yielded significantly lower pregnancy rates than fresh semen AI (16/43, 37.2% versus 25/42, 59.5%), but this was not the case in normal mares. In normal mares, hysteroscopic AI with fresh semen gave significantly (P < 0.05) better pregnancy rates than uterine body AI (27/38, 71% versus 18/38, 47.3%), whereas in problem mares this resulted in significantly lower pregnancy rates than uterine body AI (5/15, 33.3% versus 16/19, 84.2%). Our results demonstrate that for problem mares, conventional insemination into the uterine body appears to be superior to hysteroscopic insemination and in normal mares, the highest pregnancy rates can be expected by hysteroscopic insemination.

Animals↗

PubMed2002

Comparison of carotid intima-media thickness, arterial stiffness, and brachial artery flow mediated dilatation in diabetic and nondiabetic subjects (The Chennai Urban Population Study [CUPS-9]).

This study compares flow-mediated dilation (FMD) and the augmentation index (AI) in diabetic and nondiabetic subjects and correlates these measurements with carotid intima-media thickness (IMT). Fifty diabetic subjects and 50 age- and sex-matched nondiabetic control subjects were recruited from the Chennai Urban Population Study. IMT of the common carotid artery and FMD of the brachial artery were determined using high-resolution B-mode ultrasonography. AI was measured using the Sphygmocor apparatus. The mean AI of diabetic subjects was significantly higher than the nondiabetic subjects (27.48 +/- 7.41% vs 19.10 +/- 8.19%, p <0.0001). The FMD values were significantly lower among diabetic subjects compared with the nondiabetic subjects (2.1 +/- 2.95% vs 6.64 +/- 4.38%, p <0.0001). At any given age point, diabetic subjects had significantly higher AI and lower FMD values compared with nondiabetic subjects (p <0.05). In the total population, AI and FMD showed a correlation with age (p <0.001), fasting plasma glucose (p <0.01), glycosylated hemoglobin (p = 0.001), and IMT (p = 0.001). Among the nondiabetic subjects, FMD and AI showed a strong correlation with IMT. FMD also showed a strong correlation with age and systolic blood pressure, whereas AI showed a correlation with fasting plasma glucose in diabetic subjects. AI and FMD values showed a strong correlation with age. AI values increased and FMD values decreased with an increase in quartiles of IMT both in diabetic and nondiabetic subjects. Multivariate linear regression analyses in the total study population showed that age and glycosylated hemoglobin were the risk factors associated with AI and FMD, in addition to diastolic blood pressure with AI. Diabetic patients have decreased FMD and increased arterial stiffness compared with age- and sex-matched nondiabetic subjects. These functional changes correlate well with the structural changes of the arteries measured by IMT.

Blood Flow Velocity↗

PubMed1999

Recurrence of aortic insufficiency after aortic root remodeling with valve preservation.

BACKGROUND: Aortic root remodeling (ARR) has recently been proposed for patients with aortic aneurysms and valve insufficiency (AI). To define factors associated with a favorable functional outcome, a review of the mid-term results with ARR was undertaken. METHODS: Between March 1994 and October 1997, 17 consecutive patients (11 men, 6 women), aged 57 +/- 11 years (range 35-71), had elective ARR for aortic aneurysm with or without annuloaortic ectasia (13), sinus of Valsalva aneurysm (3), or chronic aortic dissection (1). Moderate or severe AI was present in 11 patients (65%). Preoperative aortic root diameter was 58 +/- 5 mm (range 51-70). ARR involved replacement of all three aortic sinuses and coronary button reimplantation, using grafts with a mean diameter of 28 +/- 2 mm (range 24-30). RESULTS: There was one early death (6%) due to multiple organ failure. Survivors were followed for 16 +/- 12 months (range 1-44). Actuarial 3-year survival was 94% +/- 6%. Discharge echocardiogram showed a decrease in AI in all patients: AI was absent in 11 (69%) and mild in 5 (31%). Recurrence of moderate or severe AI after a mean of 16 +/- 9 months (range 9-28) was noted in 6 patients (37%), 3 of whom had no AI at discharge. Five of 6 patients required aortic valve replacement. Comparison of demographic and operative variables showed that severe preoperative AI (67% vs 20%, p = 0.06), annuloaortic ectasia (100% vs 20%, p = 0.002), and cystic medial necrosis (100% vs 20%, p = 0.002) were significantly more prevalent in patients developing severe AI at follow-up. The 10 patients (63%) with absent AI showed durable competence of the valve and relief from symptoms at follow-up. CONCLUSIONS: Despite early restoration of valve competence, AI may recur and progress after ARR at medium-term follow-up in a proportion of patients. The severity of preoperative AI and the nature of aortic root disease may negatively influence the durability of repair. Continued observation of results with ARR appears mandatory to identify the appropriate surgical candidates.

Adult↗

PubMed1999

Thermodynamic prediction of active ingredient loading in polymeric microparticles.

The growing use of microparticles as a controlled-delivery system for pharmaceutical and non-pharmaceutical active ingredients (AIs) has prompted a costly trial-and-error development of new and effective microparticle systems. In order to facilitate a more rational design and optimization of AI loadings in microparticles, we have developed a molecular-thermodynamic theory to predict the loading of liquid AIs in polymeric microparticles that are manufactured by a solvent evaporation process. This process involves the emulsification of a liquid polymer solution (consisting of polymer and AI dissolved in a volatile solvent) in an aqueous surfactant solution. The theory describes the equilibrium distribution of the AI between the aqueous phase and the dispersed polymeric droplets. The universal functional activity coefficient (UNIFAC) and UNIFAC-Free Volume (FV) group-contribution methods are utilized to model the nonidealities in the water and polymeric droplet phases, respectively. The inputs to the theory are: (i) the chemical structures, densities and total masses of the manufacturing ingredients, (ii) the manufacturing temperature and (iii) the glass transition temperature of the polymer. Since surfactant concentrations exceeding the critical micellar concentration (CMC) are often required in order to stabilize the dispersed polymeric droplets during the emulsion manufacturing process, the theory also accounts for AI solubilization in surfactant micelles present in the manufacturing solution. To test the AI loading predictions, we compare theoretical predictions of AI loadings in poly(lactic acid), poly(methyl methacrylate) and polystyrene microparticles to experimentally measured ones for five model AIs with varying degrees of hydrophobicity (benzyl alcohol, n-octanol, geraniol, farnesol and galaxolide). We also demonstrate how the developed theory can be utilized to screen polymers with respect to their abilities to load a given AI, as well as to provide guidelines for manufacturing microparticles having the desired AI loading.

Drug Delivery Systems↗

PubMed1995

Derivation of frequency-gain characteristics for maximizing speech reception in noise.

Hearing aid gain-assignment schemes known as "prescriptions" were not designed for fitting hearing aids that modify their frequency responses to reduce background noise interference. Rather, prescriptions were developed for hearing aids having single, fixed frequency responses and aim to optimize speech reception in relatively quiet environments. Even though prescriptions do not apply to noisy conditions specifically, they embody the trade between maximizing speech audibility and maintaining loudness comfort that is critical to frequency-gain characteristic selection independent of whether noise is present or absent. The articulation index (AI) was used to examine the extent to which prescriptions' deference to loudness comfort causes them to fall short of maximizing speech spectrum audibility, thereby revealing (roughly) the magnitude of the loudness control built into prescriptions. AIs for speech amplified by an AI-maximizing rule (MAX AI) (Rankovic, Freyman, & Zurek, 1992) and according to several prescriptions were calculated as a function of hearing loss degree and configuration for quiet and noisy conditions. In quiet, AIs for prescriptions were similar to one another when presented with the same audiogram but were drastically smaller than MAX AIs, implying that prescriptions limit speech audibility to a large extent to prevent loudness discomfort. In noise, maximizing the AI required frequency-gain characteristics that were substantially different from prescription-assigned characteristics and that were unique to each noise/audiogram combination. A loudness constraint for the MAX AI scheme was developed to account for the gain discrepancy between prescription AIs and MAX AIs observed in the quiet condition, based on the highest comfortable loudness (HCL) equations presented by Cox (1989) in combination with a loudness model (von Paulus & Zwicker, 1972). The MAX AI scheme with the new loudness control was extended to specify frequency-gain characteristics expected to be optimal for several conditions containing noise, and examples are presented.

Hearing Aids↗

PubMed2000

Functional organization of auditory cortex in the Mongolian gerbil (Meriones unguiculatus). III. Anatomical subdivisions and corticocortical connections.

The auditory cortex of the Mongolian gerbil comprises several physiologically identified fields, including the primary (AI), anterior (AAF), dorsal (D), ventral (V), dorsoposterior (DP) and ventroposterior (VP) fields, as established previously with electrophysiological [Thomas et al. (1993) Eur. J. Neurosci., 5, 882] and functional metabolic techniques [Scheich et al. (1993) Eur. J. Neurosci., 5, 898]. Here we describe the cyto-, myelo- and chemoarchitecture and the corticocortical connections of the auditory cortex in this species. A central area of temporal cortex corresponding to AI and the rostrally adjacent AAF is distinguished from surrounding cortical areas by its koniocortical cytoarchitecture, by a higher density of myelinated fibres, predominantly in granular and infragranular layers, and by characteristic patterns of immunoreactivity for the calcium-binding protein parvalbumin (most intense staining in layers III/IV and VIa) and for the cytoskeletal neurofilament protein (antibody SMI-32; most intense staining in layers III, V and VI). Concerning the cortical connections, injections of the predominantly anterograde tracer biocytin into the four tonotopically organized fields AI, AAF, DP and VP yielded the following labelling patterns. (i) Labelled axons and terminals were seen within each injected field itself. (ii) Following injections into AI, labelled axons and terminals were also seen in the ipsilateral AAF, DP, VP, D and V, and in a hitherto undescribed possible auditory field, termed the ventromedial field (VM). Similarly, following injections into AAF, DP and VP, labelling was also seen in each of the noninjected fields, except in VM. (iii) Each field projects to its homotopic counterpart in the contralateral hemisphere. In addition, field AI projects to contralateral AAF, DP and VP, field DP to contralateral AI and VP, and field VP to contralateral AI and DP. (iv) Some retrogradely filled pyramidal neurons within the areas of terminal labelling indicate reciprocal connections between most fields, both ipsilateral and contralateral. (v) The labelled fibres within the injected and the target fields, both ipsilateral and contralateral, were arranged in continuous dorsoventral bands parallel to isofrequency contours. The more caudal the injection site in AI the more rostral was the label in AAF. This suggests divergent but frequency-specific connections within and, at least for AI and AAF, also across fields, both ipsilateral and contralateral. (vi) Projections to associative cortices (perirhinal, entorhinal, cingulate) and to other sensory cortices (olfactory, somatosensory, visual) from AAF, DP and VP appeared stronger than those from AI. These data support the differentiation of auditory cortical fields in the gerbil into at least 'core' (AI and AAF) and 'noncore' fields. They further reveal a complex pattern of interconnections within and between auditory cortical fields and other cortical areas, such that each field of auditory cortex has its unique set of connections.

Animals↗

PubMed1999

Apoptosis and mitosis in tumours of the skin and subcutaneous tissues of the dog.

The presence of apoptotic cell death was evaluated in routinely processed tissue samples of 39 neoplasms of the skin and subcutaneous tissues of the dog using the method of terminal deoxynucleotidyl transferase (T d T) mediated deoxyuridine-5'-triphosphate (d UTP)-biotin nick end labelling (TUNEL). The degree of apoptosis was related to the frequency of mitosis, an index of cell proliferation. The correlation between the apoptotic index (AI), the percentage of positive cells after randomly enumerating 1000 cells and the mitotic count (MC), the number of mitotic figures in 10 fields at a magnification of 400 times was assessed by the Spearman non-parametric correlation test. TUNEL signals were observed in all types of tumours as brown products detected in non-pyknotic nuclei, in non-identifiable rounded structures (so-called apoptotic bodies) and occasionally in the cytoplasm, either singly or in combination. An inverse relationship between AI and MC was observed in benign tumours, while no correlation was found between AI and MC in either malignant or locally invasive tumours. Among benign tumours, intracutaneous cornifying epithelioma, fibroma, haemangioma and Schwannoma had high AI and low MC, while histiocytomas had low AI and high MC and pilomatrixomas low AI and MC. All malignant tumours had low AI and high MC, except for fibrosarcomas, which had high AI and MC. Finally, higher heterogeneity was observed among locally invasive tumours, as they had high AI and low MC (squamous cell carcinomas), and low AI with either low MC (haemangiopericytomas) or high MC (basal cell tumours). The classification of the tumours according to their AI (>15.8% high and <15.8% low) and MC (>9 high, <9 low) did not reflect the clinical behaviour of some tumour types.

Adenocarcinoma↗

PubMed2000

A chimera-like alpha-amylase inhibitor suggesting the evolution of Phaseolus vulgaris alpha-amylase inhibitor.

White kidney bean (Phaseolus vulgaris) contains two kinds of alpha-amylase inhibitors, one heat-stable (alpha AI-s) and one heat-labile (alpha AI-u). alpha AI-s has recently been revealed to be a tetrameric complex, alpha(2)beta(2), with two active sites [Kasahara et al. (1996) J. Biochem. 120, 177-183]. The present study was undertaken to reveal the molecular features of alpha AI-u, which is composed of three kinds of subunits, alpha, beta, and gamma. The gamma-subunit, in contrast to the alpha- and beta-subunits that are indistinguishable from the alpha- and beta-subunits of alpha AI-s, was found to correspond to a subunit of an alpha-amylase inhibitor-like protein, which has been identified as an inactive, evolutionary intermediate between arcelin and the alpha-amylase inhibitor in a P. vulgaris defense protein family. The polypeptide molecular weight of alpha AI-u determined by the light-scattering technique, together with the polypeptide molecular weights of the subunits, suggests that alpha AI-u is a trimeric complex, alpha beta gamma. The inhibition of alpha AI-u by increasing amounts of porcine pancreatic alpha-amylase (PPA) indicates that an inactive 1:1 complex is formed between alpha AI-u and PPA. Molecular weight estimation of the complex by the light-scattering technique confirmed that it is a complex of alpha AI-u with one PPA molecule. Thus it seems probable that alpha AI-u is an evolutionary intermediate of the P. vulgaris alpha-amylase inhibitor.

Amino Acid Sequence↗

PubMed1999

Management of axillary lymph nodes in breast cancer: a national patterns of care study of 17,151 patients.

OBJECTIVE: To determine the rates of axillary lymph node dissection (ALND) and axillary irradiation (AI) in patients with breast cancer and to identify the factors influencing them. SUMMARY BACKGROUND DATA: Routine performance of ALND in the treatment of breast cancer has become controversial. AI has been proposed as an alternative to ALND, and it has been suggested that AI in addition to ALND may decrease local failure in high-risk patients. METHODS: A joint study was conducted by the Commission on Cancer of the American College of Surgeons and the American College of Radiology. A total of 17,151 patients with stage I and II breast cancer treated at 819 institutions in 1994 were studied. RESULTS: A total of 15,992 patients underwent ALND (93%). The mean ages of patients who did and did not undergo ALND were 60.4 and 73.0 years. Univariate analysis demonstrated significantly decreased rates of ALND for women age 70 or older (86% vs. 97%), patients with clinical T1 a tumors (81% vs. 93%), grade I histology (90% vs. 95%), and patients with favorable tumor types (88% vs. 94%). The ALND rate did not vary between palpable and nonpalpable tumors. Multivariate analysis of variables affecting the rate of ALND identified type of surgery, age, tumor size, histology, and payer status as significant. A total of 889 patients received AI. Patients not undergoing ALND were more likely to receive AI (10% vs. 5%). A total of 1.6% of patients with no lymph node metastasis underwent AI, 8.9% of those with one to three positive nodes underwent AI, 24.0% of those with four to nine positive lymph nodes underwent AI, and 29.9% of those with > or = 10 positive lymph nodes underwent AI. Multivariate analysis of variables affecting the proportion of patients who received AI and had undergone ALND identified nodal status and type of surgery as significant. CONCLUSIONS: Axillary lymph node dissection continues to be routinely applied in the treatment of breast cancer, and AI remains underused in patients at high risk for local regional relapse.

Adult↗

PubMed2004

Cocaine-induced 'active immobility' and its modulation by the serotonin1A receptor.

'Active immobility' (AI) is an independent behaviour that can be characterized by behavioural immobility, an increased muscular rigidity and the sustaining of an unusual posture. In previous studies with cocaine we observed, concomitant with hyperlocomotion and increased rearing activity, an increase in AI in well-habituated animals, which may constitute another 'positive' acute effect of cocaine on behaviour. The contribution of the serotonergic (5-HT) system to AI is well established. However, little information exists about the contribution of particular 5-HT-receptor subtypes. In order to examine a possible role of the 5-HT1A receptor on this effect of cocaine, we systematically re-analysed four previous experiments in well-habituated animals and one in little-habituated animals, focusing on the acute behavioural effects of cocaine on AI. We found that, in well-habituated animals, cocaine at a medium dose (10 mg/kg, i.p.) induces AI behaviour, which, however, does not correlate with cocaine effects on locomotion, rearing or grooming behaviour. However, there was no effect of cocaine (1, 5 or 15 mg/kg, i.p.) on AI in little-habituated animals. The 5-HT1A-receptor antagonist, WAY 100635 [N-[2-(4-2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane carboxamide trihydrochloride] (0.4 mg/kg, i.p.), potentiated cocaine-induced AI in well-habituated animals, while the 5-HT1A-receptor agonist, 8-OH-DPAT (0.2 mg/kg, i.p.), attenuated it. The local application of 8-OH-DPAT [8-hydroxy-2-(di-n-propylamino)tetralin] into the nucleus accumbens (0, 1, 10 micromol/l) or hippocampus (0, 0.1, 1, 10 micromol/l) modulated cocaine-induced AI in a complex way. These results showed that cocaine induces AI at a medium dose in well-habituated but not in little-habituated animals. The cocaine-induced AI in well-habituated animals can be potentiated by systemic 5-HT1A-receptor antagonism and attenuated by 5-HT1A-receptor agonism. Two experiments with local activation of postsynaptic 5-HT1A receptors revealed that both nucleus accumbens and hippocampal 5-HT1A-receptor populations are involved in the expression of cocaine-induced AI.

Animals↗

PubMed2001

Abundance of apoptotic neoplastic cells in diagnostic biopsy samples is not a prognostic factor in childhood primitive neuroectodermal tumors of the central nervous system.

PURPOSE: To assess if the abundance of apoptotic tumor cells is an independent prognostic factor in primitive neuroectodermal tumors (PNET) of the central nervous system. PATIENTS AND METHODS: Formalin-fixed paraffin-embedded tumor tissue sections from 78 clinically well-characterized children with PNET were evaluated by terminal deoxytransferase-mediated deoxyuridinie-5'-triphosphate (dUTP) nick-end labeling (TUNEL). Apoptotic indices (AI) were determined by counting TUNEL-positive tumor cells either in the highest staining region (AI hot spot) or in at least 15 randomly chosen fields (AI random). The AI hot spot and AI random were then correlated with clinical variables and survival outcome. RESULTS: AI hot spot (median 0.56%; range 0%-6.54%) and AI random (median 0.30%; range 0%-3.21%) showed considerable intertumor variability. Moreover, 53% of the evaluated PNET showed a more than two-fold difference between AI hot spot and AI random, showing important intratumoral variability of the abundance of apoptotic cells in a subset of the evaluated PNET. No significant associations were found between AI hot spot and AI random with clinical variables or survival outcome. CONCLUSION: The apoptotic index does not predict survival outcome and is not specifically associated with clinical variables of prognostic significance in childhood PNET.

Apoptosis↗

PubMed2003

The prevalence of DSM-III-R alcohol dependence in two American Indian populations.

BACKGROUND: Evidence suggests that American Indian (AI) populations may be at increased risk for problems with alcohol, but a lack of community-based research using diagnostic criteria has constrained our ability to draw inferences about the extent of severe alcohol problems, such as dependence, in AI populations. METHODS: This article draws on data collected by the American Indian Service Utilization, Psychiatric Epidemiology, Risk and Protective Factors Project (AI-SUPERPFP), which involved interviews with 3084 AI people living on or near their reservations. The AI-SUPERPFP sample was drawn from two culturally distinct tribes, which were designated with geographical descriptions: Northern Plains (NP) and Southwest (SW). Comparisons with data collected by the National Comorbidity Survey (NCS) were explored by using shared measures to situate the findings from AI-SUPERPFP in a national context. RESULTS: Lifetime rates of DSM-III-R alcohol dependence for men in both AI-SUPERPFP samples were 50% higher than those found in the NCS. Rates of lifetime alcohol dependence for women varied by sample, however; NP women had twice the rate of women in the NCS, but SW women had rates quite similar to those of NCS women. Patterns for 12-month alcohol dependence in AI-SUPERPFP were generally more similar to those found in NCS. CONCLUSIONS: The rates of DSM-III-R alcohol dependence found in AI-SUPERPFP were generally higher than US averages and justify continued attention and concern to alcohol problems in AI communities, but they are not nearly as high as those in other reports in the literature that rely on less stringent sampling methods. Furthermore, significant sociocultural influences on the correlates of alcohol dependence in AI communities are evident in these data, underscoring the need to appreciate the complex and varying influences on the patterning of alcohol problems in the diverse cultural contexts of the US.

Adolescent↗

PubMed2005

Acute secondary adrenal insufficiency after traumatic brain injury: a prospective study.

OBJECTIVE: To determine the prevalence, time course, clinical characteristics, and effect of adrenal insufficiency (AI) after traumatic brain injury (TBI). DESIGN: Prospective intensive care unit-based cohort study. SETTING: Three level 1 trauma centers. PATIENTS: A total of 80 patients with moderate or severe TBI (Glasgow Coma Scale score, 3-13) and 41 trauma patients without TBI (Injury Severity Score, >15) enrolled between June 2002 and November 2003. MEASUREMENTS: Serum cortisol and adrenocorticotropic hormone levels were drawn twice daily for up to 9 days postinjury; AI was defined as two consecutive cortisols of < or =15 microg/dL (25th percentile for extracranial trauma patients) or one cortisol of < 5 microg/dL. Principal outcome measures included: injury characteristics, hemodynamic data, usage of vasopressors, metabolic suppressive agents (high-dose pentobarbital and propofol), etomidate, and AI status. MAIN RESULTS: AI occurred in 42 TBI patients (53%). Adrenocorticotropic hormone levels were lower at the time of AI (median, 18.9 vs. 36.1 pg/mL; p = .0001). Compared with patients without AI, those with AI were younger (p = .01), had higher injury severity (p = .02), had a higher frequency of early ischemic insults (hypotension, hypoxia, severe anemia) (p = .02), and were more likely to have received etomidate (p = .049). Over the acute postinjury period, patients with AI had lower trough mean arterial pressure (p = .001) and greater vasopressor use (p = .047). Mean arterial pressure was lower in the 8 hrs preceding a low (< or =15 microg/dL) cortisol level (p = .003). There was an inverse relationship between cortisol levels and vasopressor use (p = .0005) and between cortisol levels within 24 hrs of injury and etomidate use (p = .002). Use of high-dose propofol and pentobarbital was strongly associated with lower cortisol levels (p < .0001). CONCLUSIONS: Approximately 50% of patients with moderate or severe TBI have at least transient AI. Younger age, greater injury severity, early ischemic insults, and the use of etomidate and metabolic suppressive agents are associated with AI. Because lower cortisol levels were associated with lower blood pressure and higher vasopressor use, consideration should be given to monitoring cortisol levels in intubated TBI patients, particularly those receiving high-dose pentobarbital or propofol. A randomized trial of stress-dose hydrocortisone in TBI patients with AI is underway.

Acute Disease↗

PubMed2003

Unilateral ureteropelvic junction obstruction in children: long-term followup after unilateral pyeloplasty.

PURPOSE: The benefit of surgery on renal function in unilateral ureteropelvic junction stenosis (UPJS) is still debated. We evaluated renal function outcome after unilateral pyeloplasty in 53 children. MATERIALS AND METHODS: We retrospectively reviewed 123I-hippuran renography performed at diagnosis and 5 to 15 years (mean +/- SD 7 +/- 3 years) after successful pyeloplasty. UPJS was prenatally detected in 26 children because of urinary tract infection in 17 and miscellaneous reasons in 10. Relative function (RF) and absolute function were measured on background corrected renograms. Absolute function of the affected and contralateral kidneys was determined by an accumulation index (AI), representing the percent injected dose extracted by each kidney 30 to 90 seconds after the heart peak. RESULTS: Preoperatively 33 of the 53 UPJS kidneys had a decreased AI but only 8 had a RF of less than 40%, which was improved in 7 at followup. In addition, the AI improved in 29 kidneys, of which 19 (36%) normalized. Of the UPJS kidneys 14 had an initially decreased AI that remained abnormal at followup. In these kidneys preoperative RF was less than 40% in all. At followup RF was greater than 40% in 4 children, in whom the AI of the UPJS kidney did not improve but the AI of the contralateral one decreased from supranormal to normal. Seven contralateral kidneys had a supranormal AI, whereas the AI remained normal in 3, of which the RF in the UPJS kidney remained at less than 40%. The AI and RF were normal in 20 UPJS kidneys and remained normal. CONCLUSIONS: When normal, the AI and RF reflected renal function outcome similarly. The AI added relevant information in UPJS kidneys with impaired function, showing compensation of the contralateral kidney.

Adolescent↗

PubMed2007

The relationship between aortic augmentation index and pulse wave velocity: an invasive study.

OBJECTIVES: The aortic augmentation index (AI) and aortic pulse wave velocity (PWV) are known to be indicators of arterial stiffness. However, it is not clear whether aortic AI and PWV reflect aortic stiffness in similar ways. We investigated the relationship between aortic AI and PWV by measuring them directly using a catheter technique. DESIGN AND METHODS: Forty-one patients, aged 34-79 years, were studied during diagnostic cardiac catheterization. Aortic pressures were measured using a catheter-tip manometer at two points, one in the ascending aorta and one 40 cm distally in the descending aorta. Aortic AI was defined as the difference between early and late pressure peaks divided by the pulse pressure of the ascending aorta. Aortic PWV was calculated as the distance between the two measuring sites divided by the transit time. We also examined the effects of vasodilatation on AI and PWV by the intra-aortic administration of nitroglycerin in 15 patients. RESULTS: AI was significantly related to age, systolic aortic pressure, heart rate, left ventricular ejection time, and height. Aortic PWV showed an association only with age and systolic aortic pressure. There was no significant relationship between aortic AI and PWV (r = 0.28, NS). Nitroglycerin also produced different effects on aortic AI and PWV: aortic AI was significantly decreased (-0.17, P < 0.01) after nitroglycerin, but PWV remained unchanged (+0.4 m/s, NS). CONCLUSIONS: Aortic AI and PWV cannot be used interchangeably as an index of arterial stiffness. AI may not be a true indicator of arterial stiffness, but an index of wave reflection including PWV.

Adult↗

PubMed2002

LuxS: its role in central metabolism and the in vitro synthesis of 4-hydroxy-5-methyl-3(2H)-furanone.

Many bacteria produce extracellular molecules which function in cell-to-cell communication. One of these molecules, autoinducer 2 (AI-2), was first described as an extracellular signal produced by Vibrio harveyi to control luciferase expression. Subsequently, a number of bacteria have been shown to possess AI-2 activity in their culture supernatants, and bear the luxS gene product, which is required for AI-2 synthesis. In Porphyromonas gingivalis, luxS and pfs, encoding a 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTA/SAH'ase), form an operon, suggesting that S-adenosylhomocysteine (SAH) or 5'-methylthioadenosine (MTA) serves as a substrate for AI-2 production. Cell-free extracts of Escherichia coli MG1655, but not DH5alpha (which carries a luxS frame-shift mutation) were capable of generating AI-2 activity upon addition of SAH, but not MTA. S-Ribosyl-homocysteine (RH) derived from SAH also served as a substrate in E. coli MG1655 extracts. RH-supplemented cell-free extracts of Pseudomonas aeruginosa, a bacterium that lacks luxS, only generated AI-2 activity following the introduction of a plasmid containing the Por. gingivalis pfs-luxS operon. In addition, defined in vitro systems consisting of the purified LuxS proteins from Por. gingivalis, E. coli, Neisseria meningitidis or Staphylococcus aureus converted RH to homocysteine and a compound that exhibits AI-2 activity.4-Hydroxy-5-methyl-3(2H)-furanone was identified by mass spectrometry analysis as a major product formed in this in vitro reaction. In E. coli MG1655, expression of T3SH [the bacteriophage T3 S-adenosylmethionine (SAM) hydrolase] significantly reduced AI-2 activity in culture supernatants, suggesting that AI-2 production is limited by the amount of SAH produced in SAM-dependent transmethylase reactions. The authors suggest that the LuxS protein has an important metabolic function in the recycling of SAH. They also show that Ps. aeruginosa is capable of removing AI-2 activity, implying that this molecule may act as a nutrient. In many bacteria AI-2 may in fact represent not a signal molecule but a metabolite which is released early and metabolized in the later stages of growth.

Bacterial Proteins↗

PubMed2006

Milk progesterone profile at and after artificial insemination in repeat-breeding cows: effects on conception rate and embryonic death.

The aim of this study was to investigate whether the skim milk progesterone concentrations at artificial insemination (AI) and day of rise of post-ovulatory progesterone concentration thereafter affect the conception and embryonic death rates in repeat-breeding cows. Milk samples were obtained from 96 repeat-breeding cows that failed to conceive to three or more AIs. The samples were taken from the cows at the day of AI and three times/week until day 45 post-AI. Skim milk was obtained after centrifugation and used for progesterone assay. The cows with a progesterone concentration more than 0.5 ng/ml at AI showed a significantly higher incidence of late embryonic death than those having a progesterone concentration<0.5 ng/ml at AI (p<0.01). As the progesterone level at insemination rose, conception rate declined. A negative correlation was shown between conception rate and skim milk progesterone level at AI. Of 56 cows showing a rise of progesterone to 1 ng/ml or more within 6 days after AI, 28 cows (50%) conceived. On the contrary, only eight of 39 cows (20.5%) conceived when the progesterone rose up to 1 ng/ml after day 6 post-AI. We concluded that increased progesterone concentration at the time of AI and delayed rise of progesterone post-AI might lead to decrease in fertility in repeat-breeding cows.

Animals↗

PubMed2005

Serial tumour blood-flow measurements in androgen-dependent and -independent Shionogi tumour models.

OBJECTIVE: To investigate the relationship between blood supply and hormonal status of hormone-dependent and -independent tumours in mice. MATERIALS AND METHODS: Contrast-enhanced dynamic magnetic resonance imaging (MRI) was used to measure tumour blood flow (TBF) in Shionogi tumours implanted subcutaneously in mice. Serial measurements were taken throughout the initial tumour growth period, and during regression and subsequent androgen-independent (AI) relapse of the tumours in male mice, and throughout the growth of AI tumours in female mice. Average TBF values and coefficients of variation were calculated from tumour tissue perfusion maps reconstructed from MRI data. The Tukey-Kramer test was used to identify differences between androgen-dependent (AD), male AI and female AI tumours. RESULTS: The mean TBF strongly depended on tumour size in all three stages of the tumour growth cycle. AI tumours had a significantly higher TBF than AD tumours, with mean (sd) values of 0.8 (0.3) (male AI) and 0.27 (0.1) mL/g/min (AD), (P < 0.001), and 0.61 (0.31) (female AI) and 0.27 (0.1) mL/g/min (AD) (P < 0.01), respectively. Tumour tissue perfusion was more homogenous in AI than in AD tumours, with a coefficient of variation of 0.91 (0.31) in male AI and 1.89 (0.48) in AD tumours (P < 0.001), and 1.47 (0.38) in female AI and 1.89 (0.48) in AD tumours (P < 0.05). CONCLUSIONS: AI Shionogi tumours have a higher TBF than AD tumours; this could have implications in the diagnosis, prognosis, therapy and monitoring of hormone-sensitive tumours.

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