ISIS 4: clinical controversy regarding magnesium infusion, thrombolytic therapy, and acute myocardial infarction

Magnesium (Mg) infusions over 24 hours were given to patients with suspected acute myocardial infarction (AMI) at least 2 hours after thrombolysis. Patients showed no benefit and even some increased risk in contrast to reduction in mortality obtained by Mg therapy in smaller trials. Results of all of the studies were pooled and statistically analyzed, according to a fixed-effects model that is inappropriate for studies of different protocols. The panel concluded that further study of Mg in AMI is not needed. This conclusion has been questioned.     

Fast and one-step folding of closely and distantly related homologous proteins of a four-helix bundle family

Bovine acyl-coenzyme A binding protein is a four-helix bundle protein belonging to a group of homologous eukaryote proteins that binds medium and long-chain acyl-coenzyme A esters with a very high affinity. The three-dimensional structure of both the free and the ligated protein together with the folding kinetics have been described in detail for the bovine protein and with four new sequences reported here, a total of 16 closely related sequences ranging from yeasts and plants to human are known. The kinetics of folding and unfolding in different concentrations of guanidine hydrochloride together with equilibrium unfolding have been measured for bovine, rat and yeast acyl-coenzyme A binding protein. The bovine and rat sequences are closely related whereas the yeast is more distantly related to these. In addition to the three natural variants, kinetics of a bovine mutant protein, Tyr31 --> Asn, have been studied. Both the folding and unfolding rates in water of the yeast protein are 15 times faster than those of bovine. The folding rates in water of the two mammalian forms, rat and bovine, are similar, though still significantly different. A faster unfolding rate both for rat and the bovine mutant protein results from a lower stability of the native states of these. These hydrophobic regions, mini cores, have been identified in the three-dimensional structure of the bovine protein and found to be formed primarily by residues that have been conserved throughout the entire eukaryote evolution from yeasts to both plants and mammals as seen in the sample of 16 sequences. The conserved residues are found to stabilize helix-helix interactions and serve specific functional purposes for ligand binding. The fast one-step folding mechanism of ACBP has been shown to be a feature that seems to be maintained throughout evolution despite numerous differences in sequence and even dramatic differences in folding kinetics and protein stability. The protein study raises the question to what extent does the conserved hydrophobic residues provide a scaffold for an efficient one-step folding mechanism.     

Topography of the flank wear surface

In many applications, topography represents the main external features of a surface. This paper describes the topography of the flank wear surface and also presents the relationship between the maximum flank wear and the topography parameters (roughness parameters) of the flank wear surface during the turning operation. A modern CNC lathe machine (Okuma LH35-N) was used for the machine turning operation. Three-dimensional surface roughness parameters of the flank wear surface were measured by a surface texture instrument (from Talysurf series) using surface topography software (Talymap). Based on the resulting experimental data, it is found that as the flank wear increases, the roughness parameters (sR_a, sR_q, and sR_t) on the flank surface increase significantly. The greater the roughness value of the flank wear surface, the higher the friction of the tool on the workpiece and the greater the heat generation that will occur, thus ultimately causing tool failure. On the other hand, positive skewness (sR_sk) indicates the presence of a small number of spikes on the flank surface of the cutting tool, which could quickly wear off during the machining process.     

Thermal error measurement and modelling in machine tools.: Part I. Influence of varying operating conditions

Thermal error in machine tools has been observed to be closely linked to the temperature of critical elements of the machine. It was found, in the experiments conducted herein, that there was a significant increase in the axis positioning error on account of an increase in the temperature of the machine elements due to continuous operation. However, it was also observed that the specific operating parameters of the test cycles carried out also significantly affected the positioning error. Different sets of operating parameters generated significantly different error values even though the temperature of the machine elements generated by those operating conditions was similar. As such, this observation forms a very important consideration in the development of a generic thermal error compensation system. It appears to indicate that such a system needs to be capable of evaluating the compensation depending upon the temperature values of the machine elements as well as account for the effect that different operating parameters induce upon the positioning error under the same thermal condition of the machine. This paper attempts to analyse the thermal behaviour of a three-axis vertical machining centre under the influence of various operating parameters and, through the experimental results obtained, point out and explain the effect of these parameters on the axis positioning error. This behaviour forms the basis of an improved modelling methodology that is presented separately in Part II of this paper.     

Long-term follow-up on hydroxylapatite-coated cylindrical dental implants: a comparison between developmental and recent periods

PURPOSE: To compare success rates for dental implants placed from 1985 through 1988 and from 1989 through 1991, and to investigate the factors associated with success or failure. PATIENTS AND METHODS: All hydroxylapatite-coated cylindrical implants placed from 1985 through 1991 were followed yearly. Lifetable survival analyses compared implant success for a "developmental period" from 1985 through 1988 (4 to 8 years follow-up) and a "recent period" from 1989 through 1991 (1 to 4 years follow-up). Reasons for success or failure, time from implant placement to removal related to failure reason, outcome after implant removal, and a morbidity analysis are included. RESULTS: The 7 to 8-year cumulative success rate for all implants placed in the developmental period (maxilla and mandible combined) was 86.5%; it was 84.2% for all maxillary implants and 87.5% for all mandibular implants. The cumulative success rate for all implants placed in the recent period was 97.5%; it was 97.5% for all maxillary implants and 97.6% for all mandibular implants. The difference between the two periods was statistically significant only for the anterior maxilla. Regression analysis on the interval success rates indicates that interval failure did not follow a linear relationship with time. The most common reasons associated with failure were lack of keratinized gingiva, poor oral hygiene, mechanical overload, and malposition. CONCLUSION: Comparison with previously reported cumulative success rates indicated learning curve experiences comparable with other implant systems. Improvements in hardware, surgical and prosthetic techniques, and patient selection have led to an improvement in success rates with the recent period implants.     

Arginine 206 of the C5a receptor is critical for ligand recognition and receptor activation by C-terminal hexapeptide analogs

C5a is a 74-amino-acid glycoprotein whose receptor is a member of the rhodopsin superfamily. While antagonists have been generated to many of these receptors, similar efforts directed at family members whose natural ligands are proteins have met with little success. The recent development of hexapeptide analogs of C5a has allowed us to begin elucidation of the molecular events that lead to activation by combining a structure/activity study of the ligand with receptor mutagenesis. Removal of the hexapeptide's C-terminal arginine reduces affinity by 100-fold and eliminates the ability of the ligand to activate the receptor. Both the guanidino side chain and the free carboxyl of the arginine participate in the interaction. The guanidino group makes the energy-yielding contact with the receptor, while the free carboxylate negates "electrostatic" interference with Arg-206 of the receptor. It is the apparent movement Arg-206 induced by this set of interactions that is responsible for activation, since conversion of Arg-206 to alanine eliminates the agonist activity of the hexapeptides. Surprisingly, activation is a nearly energy-neutral event and may reflect the binding process rather than the final resting site of the ligand.     

The North Carolina Breast Cancer Screening Program: foundations and design of a model for reaching older, minority, rural women

Breast cancer screening programs do not reach all women at the same rate. Screening mammography use varies according to sociodemographic characteristics; mammography utilization is highest among women in their fifties but then decreases with age. In North Carolina, breast cancer is a particular burden for Black and lower-income women. Black women are more likely to be diagnosed with late stage disease, and their rate of breast cancer mortality is higher than it is for White women even though the incidence in White women is greater. Older, Black, and low-income women are less likely to obtain screening by mammography and clinical breast examination. The Black-White gap is even more pronounced among rural women, in part because they are more likely to be poor. The North Carolina Breast Cancer Screening Program (NC-BCSP) was established to increase the rate of regular mammography screening by an absolute 20% in 3 years among older Black women ages 50 and older in five rural counties in the eastern part of the state. In this paper, we describe the genesis of this comprehensive community intervention model, highlighting the behavioral science constructs, health education principles, and theories of behavioral and organizational change that form its conceptual foundation. NC-BCSP's theoretical foundations include the social ecological perspective, the PRECEDE model of health promotion, the Health Belief Model of individual change, and the "stages of change" transtheoretical model. We also review the experiences and lessons learned from two previous outreach initiatives in North Carolina that provided valuable "lessons" in the development of the NC-BCSP intervention model. In the second half of the paper, we describe the actual NC-BCSP interventions, activities, and evaluation tools, citing specific examples of how the underlying theories are implemented. NC-BCSP's goal goes beyond individual behavior change to raise low mammography screening rates among Black women in rural North Carolina. Its ultimate objective is to create linkages across agencies, and between agencies and communities, that will endure after the research project ends.     

Localization of atrial natriuretic peptide receptors in the rat tongue and hard palate

The effect of a naturally occurring plant phenolic constituent (the acylphloroglucinol derivative, jensenone, derived from Eucalyptus jensenii) on the food intake of two folivorous marsupials, the common ringtail (Pseudocheirus peregrinus) and the common brushtail possum (Trichosurus vulpecula) was studied. When fed diets containing varying concentrations of jensenone, both species regulated their intake of jensenone so as not to exceed a ceiling intake. This ceiling was about twice as high for common ringtails as for common brushtails from northern Australia. Southern populations of common ringtails showed greatly reduced capacities to tolerate jensenone. When common brushtails were injected (0.5 mg.kg-0.75 body mass) with ondansetron (a selective antagonist of serotonin 5HT3 receptors), they ate significantly more jensenone than animals injected with physiological saline. The same pattern was observed when common ringtails were fed diets containing both jensenone and ondansetron (0.0035 mg.g-1 wet mass of diet). Ondansetron injection had no effect on food intake when the food did not contain jensenone while the addition of higher doses of ondansetron to diets of common ringtails very slightly reduced food intakes of a non-jensenone diet. When common brushtails were given 50 mg of jensenone by gastric lavage, their average subsequent intake of dietary jensenone matched the difference between the daily threshold and the dose given, although the response of individuals was highly variable. Lavage with water alone had no effect on subsequent jensenone intake compared with the pre-dose period. We interpret these results as evidence that the antifeedant effects of jensenone and related compounds are partly mediated by serotonin action on 5HT3 receptors most likely via "nausea" to condition a food aversion.     

Isolation and characterization of a novel facultatively alkaliphilic Nitrobacter species, N. alkalicus sp. nov

BACKGROUND: The American College of Rheumatology (ACR) established criteria to discriminate among patients with seven types of vasculitis. Although designated as "classification criteria" for research, these criteria are often used for diagnosis. OBJECTIVE: To examine the operating characteristics of the 1990 ACR classification criteria in the diagnosis of Wegener granulomatosis, giant-cell arteritis, polyarteritis nodosa, and hypersensitivity vasculitis. DESIGN: Prospective cohort study. SETTING: University medical center and Veterans Affairs medical center. PATIENTS: 198 consecutive patients referred to rheumatologists for evaluation of possible vasculitis. Measurements: Blinded chart audits were done to classify patients according to the 1990 ACR classification criteria for Wegener granulomatosis, polyarteritis nodosa, giant-cell arteritis, and hypersensitivity vasculitis on the basis of the patients' initial presentation. Chart audits done 2 to 8 months after baseline provided the patients' final diagnoses, which were considered the gold standard, as in the development of the ACR criteria. Test operating characteristics of the ACR classification criteria were calculated according to 2 x 2 tables for the entire cohort and for only the patients with a final diagnosis of vasculitis. RESULTS: Vasculitis was diagnosed in 51 (26%) patients. Thirty-eight (75%) of 51 patients with vasculitis and 31 (21%) of 147 patients without vasculitis met ACR criteria for one or more types of vasculitis. The positive predictive values for the four vasculitides according to ACR criteria were 17% to 29% for the entire cohort and 29% to 75% for only the patients with a final diagnosis of vasculitis. CONCLUSION: The 1990 ACR classification criteria function poorly in the diagnosis of specific vasculitides.