NEHRP Provisions for 1994 for Nonstructural Components

The recently published 1994 National Earthquake Hazards Reduction Program (NEHRP) provisions include new and substantially improved provisions for the seismic design of nonstructural components, including architectural, mechanical, and electrical components. The provisions are a significant departure from the 1991 NEHRP provisions and other seismic provisions, such as those offered by the 1994 Uniform Building Code (UBC). The design-force provisions are rationally derived and consider actual in-structure acceleration data recorded in recent significant California earthquakes. Also considered in the design-force equations are the dynamic properties of the components, the location of the component within the supporting structure, the safety and operational importance of the component, and the component's anchorage ductility and energy-absorption capability. The resulting force requirements of the new recommendations are compared with the 1991 NEHRP provisions and the 1994 UBC requirements. In addition, explicit design displacement provisions are introduced and discussed.     

A rare and little known variant of hypospadias

Hypospadia is a congenital defect presenting as different variants of dysplasia of the distal urethra with ectopy of the urethral external orifice and distortion of the penis. A variant of hypospadia not yet described in Russian medical literature was observed in a newborn boy. He had normal penis and scrotum, but on the under-side of the penis there was a site of thin skin protruding as a resonance bag in urination. At the site of the thin skin the back urethral wall was absent with a cavity covered by the thin skin. In urination urine filled the cavity blowing up the skin above it to the form of the resonance bag. This variant of hypospadia was designated as segmental urethral hypoplasia.     

Cocaine-induced activation of striatal neurons during focused stereotypy in rats

As psychomotor stimulants, both amphetamine and cocaine elicit episodes of repetitive motor activation (focused stereotypy) known to involve the mesostriatal dopamine system. During amphetamine-induced focused stereotypy, motor-related neurons in the striatum respond with either an excitation or inhibition, depending on dose and behavioral pattern, whereas nonmotor-related units are inhibited. To assess striatal activity during the focused stereotypy induced by cocaine, both types of striatal units were recorded in ambulant rats. Either 20 or 40 mg/kg cocaine caused highly focused sniffing and head bobbing, which occurred in conjunction with activation of both motor- and nonmotor-related neurons. The activation of motor-related units was evident even when firing rate was compared during periods of matched pre- and post-drug behavior, arguing against movement as the sole basis for the drug-induced neuronal excitation. Subsequent administration of haloperidol (1.0 mg/kg) reversed but did not completely block the neuronal activation, while the behavioral response shifted away from focused stereotypy toward an increase in ambulation. Thus, the level of activation of both motor- and nonmotor-related striatal neurons may play a critical role in the behavioral response pattern induced by cocaine.     

Classical/nonclassical hybrid cannabinoids: southern aliphatic chain-functionalized C-6beta methyl, ethyl, and propyl analogues

The stereoelectronic requirements for interaction of the southern aliphatic hydroxyl of cannabimimetic pharmacophores with the CB1 and CB2 receptors are explored. The stereoselective syntheses of three series of classical/nonclassical hybrid cannabinoids are described. These compounds were designed to investigate the importance of the southern aliphatic hydroxyl (SAH) pharmacophore for cannabimimetic activity. Variation in the chain length of the SAH moiety in these 6beta-(hydroxyalkyl)dihydrobenzopyran analogues, from 6beta-hydroxymethyl to 6beta-(omega-hydroxyethyl) and 6beta-(omega-hydroxypropyl), and the effects of replacing the hydroxyl functionality by hydride and iodide are reported. Our results indicate that the SAH pharmacophore has less pronounced effects than the C-3 aliphatic chain on cannabinoid activity. Furthermore, it appears that this southern molecular component is capable of interacting with two different subsites on the receptor and that the nature of this interaction is determined by the terminal substituent on the C-6beta alkyl group. One of the subsites can accommodate the relatively polar SAH pharmacophore, while the second subsite interacts with more hydrophobic C-6beta substituents and can accommodate large spherical pharmacophores separated by three methylene carbons from the tricyclic cannabinoid template.     

Fine needle aspiration cytology in a rural setting

OBJECTIVE: To compare, contrast and analyze the value and limitations of fine needle aspiration (FNA) cytology and core biopsy (CB) in a rural setting. STUDY DESIGN: Retrospective analysis of 100 FNA cytology and 100 CB results of mass lesions from 193 patients matched for age, sex and body organs, and referred for FNA or CB in rural New South Wales, Australia, between September 1990 and May 1996. RESULTS: FNA cytology and CB results from 193 patients were analyzed, based on anatomic location and cytologic criteria. Sites included lung, retroperitoneum, liver, breast, kidney, pancreas and ovary. The FNA group contained 6 inadequate, 14 benign, 3 atypical, 6 suspicious and 71 malignant cases, whereas the CB group had 1 inadequate, 24 benign and 75 malignant conditions. The inadequate samples in both groups were due to technical difficulty in obtaining representative material. The indeterminate (atypical and suspicious) group, which was the main pitfall of FNA, contained 4 low grade carcinomas, 3 low grade non-Hodgkin's lymphomas and 2 fibrocystic breast changes. The benign FNA group comprised 8 cysts, 5 inflammatory/reactive conditions and 1 benign tumor/hamartoma, whereas the benign CB group contained 11 cysts, 9 inflammatory/reactive conditions and 4 benign tumors. CONCLUSION: FNA was comparable to CB at most anatomic sites. CB occasionally offered additional information. This slight advantage was due to the availability of tissue from the first and often the only pass for assessment of architecture and performance of ancillary tests, which obviated the need for further sampling. On-site assessment of the core imprints at the time of the procedure by the highly skilled and experienced interventional cytopathologist was responsible for limiting the number of attempts to one core in most of the instances, therefore minimizing complications. Pathologists are encouraged to become more familiar with the criteria of aspiration cytology, which has proven its validity in the new cost-conscious environment. Despite the recent surge in the popularity of core biopsy, FNA cytology, when practiced in a multidisciplinary setting, with involvement of pathologists, radiologists and clinicians, is an extremely accurate test with very high sensitivity, which approaches that of surgical pathology, and specificity very similar to that of frozen section. FNA has a positive predictive value for a malignant diagnosis of almost 100%. FNA is a well-tolerated, relatively noninvasive test with a very low risk of complications.     

Development of orally active oxytocin antagonists: studies on 1-(1-[4-[1-(2-methyl-1-oxidopyridin-3-ylmethyl)piperidin-4-yloxy]-2- methoxybenzoyl]piperidin-4-yl)-1,4-dihydrobenz[d][1,3]oxazin-2-one (L-372,662) and related pyridines

The previously reported oxytocin antagonist L-371,257 (2) has been modified at its acetylpiperidine terminus to incorporate various pyridine N-oxide groups. This modification has led to the identification of compounds with improved pharmacokinetics and excellent oral bioavailability. The pyridine N-oxide series is exemplified by L-372,662 (30), which possessed good potency in vitro (Ki = 4.1 nM, cloned human oxytocin receptor) and in vivo (intravenous AD50 = 0.71 mg/kg in the rat), excellent oral bioavailability (90% in the rat, 96% in the dog), good aqueous solubility (>8.5 mg/mL at pH 5.2) which should facilitate formulation for iv administration, and excellent selectivity against the human arginine vasopressin receptors. Incorporation of a 5-fluoro substituent on the central benzoyl ring of this class of oxytocin antagonists enhanced in vitro and in vivo potency but was detrimental to the pharmacokinetic profiles of these compounds. Although lipophilic substitution around the pyridine ring of compound 30 gave higher affinity in vitro, such substituents were a metabolic liability and caused shortfalls in vivo. Two approaches to prevent this metabolism, addition of a cyclic constraint and incorporation of trifluoromethyl groups, were examined. The former approach was ineffective because of metabolic hydroxylation on the constrained ring system, whereas the latter showed improvement in plasma pharmacokinetics in some cases.     

On vitamin B1 metabolism in avitaminosis and its correction with thiamine and taurine

The levels of phosphate esters and the activities of thiamine biotransformation enzymes in the blood and tissues of albino rats were studied during oxythiamine-induced B1 deficiency and after metabolic correction with thiamine and taurine. Among thiamine phosphates, the most informative indicators of thiamine deficiency were shown to be triphosphate esters and free thiamine diphosphate. The biosynthetic enzymes thiamine kinase and thiamine diphosphate kinase played a decisive role in maintaining the initial rate and in recovering the physiologically active forms of vitamin B1. The activation of hydrolytic enzymes of thiamine phosphate esters occurred by producing abundant free thiamine diphosphate and thiamine triphosphate. Within the first hours, taurine favoured the acceleration of phosphoester biosynthesis and, accumulating in the tissues, inhibited vitamin phosphorylation reactions.