Evaluation of the activity of a novel metabotropic glutamate receptor antagonist (+/-)-2-amino-2-(3-cis and trans-carboxycyclobutyl-3-(9-thioxanthyl)propionic acid) in the in vitro neonatal spinal cord and in an in vivo pain model.

The cyclobutylglycine (+/-)-2-amino-2-(3-cis and trans-carboxycyclobutyl-3-(9-thioxanthyl)propionic acid) (LY393053) has been identified as a functionally potent metabotropic glutamate receptor antagonist. It is most potent on the two group I metabotropic glutamate receptors, 1alpha and 5alpha, with IC50 values of 1.0+/-0.4 microM and 1.6+/-1.4 microM, respectively. In this study, LY393053 has also been evaluated electrophysiologically on native group I metabotropic glutamate receptors in an in vitro spinal cord preparation as well as behaviourally, in a mouse model of visceral pain. LY393053 dose-dependently antagonised group I agonist, (RS)-3, 5-dihydroxyphenylglycine, or a broad-spectrum agonist (1S,3R)-amino-1,3-cyclopentanedicarboxylic acid-induced depolarisation of spinal motoneurons. The apparent Kd values were estimated to be 0.3 microM against (RS)-3, 5-dihydroxyphenylglycine-induced depolarisation and 0.5 microM against (1S,3R)-amino-1,3-cyclopentanedicarboxylic acid-induced depolarisation, respectively. On the other hand, the dorsal root-ventral root potential elicited at 8 x threshold was depressed by LY393053 with IC50 values of 9.0+/-0.7 microM and 12.7+/-1.7 microM on monosynaptic and polysynaptic responses, respectively. When investigated using the mouse acetic acid writhing test, LY393053 showed significant analgesic effects at doses of 1-10 mg/kg intraperitoneally. An ED50 value of 6.0 mg/kg was obtained in this test. By revealing a potent effect of LY393053 in antagonising the native group I metabotropic receptor-mediated responses in the spinal cord in rodents, and an antinociceptive efficacy in a mouse visceral pain model, these results, therefore, provide additional evidence in support of the analgesic potential of metabotropic glutamate receptor antagonists.

Neutron anatomy.

The familiar extremes of crystalline material are single-crystals and random powders. In between these two extremes are polycrystalline aggregates, not randomly arranged but possessing some preferred orientation and this is the form taken by constructional materials, be they steel girders or the bones of a human or animal skeleton. The details of the preferred orientation determine the ability of the material to withstand stress in any direction. In the case of bone the crucial factor is the orientation of the c-axes of the mineral content-the crystals of the hexagonal hydroxyapatite- and this can readily be determined by neutron diffraction. In particular it can be measured over the volume of a piece of bone, utilising distances ranging from 1 mm to 10 mm. The major practical problem is to avoid the intense incoherent scattering from the hydrogen in the accompanying collagen; this can best be achieved by heat-treatment and it is demonstrated that this does not affect the underlying apatite. These studies of bone give leading anatomical information on the life and activities of humans and animals-including, for example, the life history of the human femur, the locomotion of sheep, the fracture of the legs of racehorses and the life-styles of Neolithic tribes. We conclude that the material is placed economically in the bone to withstand the expected stresses of life and the environment. The experimental results are presented in terms of the magnitude of the 0002 apatite reflection. It so happens that for a random powder the 0002, 1121 reflections, which are neighbouring lines in the powder pattern, are approximately equal in intensity. The latter reflection, being of manifold multiplicity, is scarcely affected by preferred orientation so that the numerical value of the 0002/1121 ratio serves quite accurately as a quantitative measure of the degree of orientation of the c-axes in any chosen direction, for a sample of bone.

Medial vs lateral wall pyriform sinus carcinoma: implications for management of regional lymphatics.

BACKGROUND: Our purpose in performing this review is to analyze the relationship between the anatomic site of hypopharyngeal lesions and the pattern of recurrent disease, particularly cervical recurrence. This clinical information can subsequently be used to influence treatment options. METHODS: The records of 169 patients with carcinoma of the hypopharynx treated between 1975 and 1986 were reviewed retrospectively. Patients were classified as having medial wall pyriform sinus disease (MP) lesions, lateral wall pyriform sinus (LP) lesions, posterior wall (PW), or postcricoid (PC) lesions. All patients were followed a minimum of 36 months. Patients with evidence of recurrent carcinoma were characterized according to the site of recurrence. RESULTS: Recurrent carcinoma in the hypopharynx was noted in seven (4%) of 169 patients. Cervical metastases was the sole site of failure in 27 (16%) of 69 patients, whereas distant metastases developed in 25 (15%) of 169 patients. Failure in the contralateral unoperated neck occurred in 14% (10/71) of patients with MP lesions and, in contrast, 5% (4/76) LP patients. This difference was statistically significant (p = 0.04). Radiotherapy was not effective in preventing cervical recurrence in 20 (74%) of 27 overall neck failures and 11 (79%) of 14 contralateral NO neck failures. CONCLUSION: These data suggest that patients with carcinoma involving the MP are at greater risk for contralateral cervical metastases. We recommend bilateral neck dissection be offered to patients with MP lesions.

Auditory comprehension of "yes-no" questions by adult aphasics.

Two groups of adult aphasics were administered four different types of auditory-verbal "yes-no" questions. One group received questions including egocentric, environmental, pictorial, and relationship items in a consistent order. The second group received the same questions in random order. Support was found for the existence of a hierarchy of difficulty among the types of auditory-verbal "yes-no" questions. There was no significant difference between the two groups' performance even though the consistent presentation group was slightly superior to the random order group on the auditory-verbal "yes-no" questions.

The orientation of the mineral crystals in the radius and tibia of the sheep, and its variation with age.

The direction of preferred orientation of the hydroxyapatite crystals in both the tibia and radius of the sheep is close to the long axis of the bone, notwithstanding the angle of about 30 degrees which, for the tibia, exists between the long axis and the direction of principal dynamic strain during locomotion. For both bones the orientation of the cranial cortex, which is a tension surface during locomotion, is about 40% larger than the caudal. The variation with age of the magnitude of the preferred orientation for the sheep bones is contrasted with what has been reported earlier for the human femur. Notably, for the sheep, both bones show substantial orientation at birth--having increased steadily during gestation--so that the animal is able to stand and walk at the outset.

Anabolic steroids: interest among parents and nonathletes.

To determine the nature and extent of public interest in anabolic steroids, questionnaires were sent to 1290 family physicians and pediatricians in Texas. Of the 517 respondents, 55% reported being asked about steroids or seeing possible steroid users in their practices during the previous 5 years; 261 physicians (51%) reported 1682 inquiries. High school aged boys were the subject of 60% of all inquiries, 26% of which were made by parents and were exclusively related to sports. Football and athletics in general were the most common reasons for inquiry (62%), but 36% of the adolescents were interested in steroids for psychosocial reasons. Nearly 60% of the inquiries by adolescents and 36% of those by parents were considered to be serious, as opposed to casual. All inquiries regarding adolescents were for boys, and less than 1% were nonwhite. On hundred seventy-seven physicians (34%) reported 802 possible steroid users. Only 17 patients fit the stereotype of a steroid user (ie, competitive bodybuilders or professional and collegiate athletes); football players comprised 12.4% of the total. Those thought to be using steroids for psychosocial reasons equaled almost 10% of the total. All those identified as steroid users were male and only nine were nonwhite. The survey results suggest that interest in and use of anabolic steroids are common, rather than the exclusive purview of competitive athletes. This study is the first to demonstrate parental interest in anabolic steroids.

Intellective functioning and strategy use in children with insulin-dependent diabetes mellitus.

The cognitive development of children with either early or late onset insulin-dependent diabetes mellitus (IDDM) was investigated with tasks measuring intellectual ability, memory, and academic progress. In addition, children's perceptions of their competence and parents' perspectives on family functioning and their children's behavior were compared. It was found that children with IDDM scored within the normal range on standardized measures of intelligence and academic performance but evidenced some school difficulties, as reflected in subscale performance as well as in their need of remedial education services. Further, evidence was found to suggest deficiencies in children's use of strategies to organize and recall information, particularly for those with early onset of disease. Children's perceived self-competencies and parents' reports of family functioning were strikingly similar across groups. However, parents of those children whose illness began prior to age 5 reported their children to have poor attention spans and difficulty completing tasks.

Epidural anaesthesia attenuates the catecholamine response to hypoventilation.

The effect of a high epidural block on the catecholamine response to hypoventilation was studied in six unanesthetized dogs given intravenous sufentanil (15 micrograms.kg-1). Sufentanil alone resulted in a increase of norepinephrine (NE) concentration from 108 +/- 73 pg.ml-1 to 843 +/- 399 pg.ml-1 and epinephrine (E) from 279 +/- 80 pg.ml-1 to 2010 +/- 1416 pg.ml-1. At least one week later, an epidural block to T1 was achieved using 8-10 ml, two per cent lidocaine. Plasma NE and E decreased after EA to about 50 per cent of resting baseline measurements. The addition of sufentanil increased NE and E levels to reach approximately the resting base-line levels. In all dogs intravenous sufentanil resulted in bradypnoea, bradycardia, hypoxaemia, and hypercarbia. Intravenous lidocaine infusions had no significant effect on plasma catecholamine levels when plasma lidocaine levels ranged from 1.7 micrograms.ml-1 to 5.3 micrograms.ml-1. We conclude that a high two per cent lidocaine epidural block attenuates the catecholamine response to hypoventilation in dogs, but the persistence of baseline plasma levels of NE and E suggests that the efferent sympathetic block by high EA is incomplete.

The dependence of human bone texture on life style.

Neutron diffraction has been used to determine the preferred orientation of the hydroxyapatite crystals at the lower front edge of the tibia. The bones are compared for two Neolithic Orkney tribes. At Isbister, a muscular tribe on a hilly site engaged in heavy uphill work, whereas a tribe at Quanterness lived on level ground. The two sets are contrasted with the texture of present-day amputations. Values of 16, 8 and 3 are found for an 'index of manoeuvrability' for the Isbister, Quanterness and modern ankles, respectively.

Anabolic steroids and growth hormone in the Texas Panhandle.

We conducted a survey of family physicians and general pediatricians in the Texas Panhandle to learn about patient interest in anabolic steroids and growth hormone. Responses were anonymous. Fifty-five percent of those surveyed responded. Of these, 48.5% had received inquiries about anabolic steroids, 29% had seen patients they felt were taking steroids, and 15% had received inquiries concerning growth hormone. All inquirers about steroids and growth hormone and all perceived steroid users were male, and almost all were white. Adolescents (from 13 to 17 years old) accounted for 48% of the inquiries, young adults (18 to 25 years old) 48%, and adults 4%. Twenty percent of the inquiries were made by parents. Adolescents accounted for 31% of the perceived steroid users, young adults 68%, and adults 1%. Weight lifters and body builders comprised 60% of this group, football players 26%, and those taking steroids primarily for psychological reasons 13%. Nearly all inquiries about growth hormone were made by parents, and 44% were made on behalf of children for purposes of augmenting their normal height or for athletic enhancement.

Humoral immune response to selected subgingival plaque microorganisms in insulin-dependent diabetic children.

Juvenile diabetics have been shown to have an increased susceptibility to gingivitis and periodontitis following puberty. However, little data are available on changes in the microbial flora that occur at the onset of puberty. This study was performed to determine if antibacterial antibody titers to selected periodontal disease-associated microorganisms might be helpful in revealing changes in plaque flora at the onset and conclusion of puberty. Sera was obtained from 35 subjects (ages 7 to 18 years) selected from a population of insulin-dependent diabetics. The subjects were given a thorough medical examination which included an assessment of sexual maturation and a dental examination which included the recording of onset and magnitude of bleeding according to the papillary bleeding score. Antibody titers to A. naeslundii (AN), B. intermedius (BI), B. gingivalis (BG), F. nucleatum (FN), A. actinomycetemcomitans (AA), C. ochracea (CO) and T. denticola (TD) were determined using the microELISA. Stratification of antibody titers by age groups (less than or equal to 12 years, 12 to 15 years, greater than 15 years) revealed that titers to AN increased significantly (P less than 0.025, ANOVA) and progressively (P less than 0.05, regression analysis) with increasing age. In contrast, the titers to FN were maximal in the under 12 year group and decreased with age (ANOVA, P less than 0.05; regression analysis, P less than 0.05). There were no significant variations in titers observed for the other microorganisms. Stratification by sexual maturity revealed a similar progressive decrease of the titer to FN (ANOVA, P less than 0.05; regression analysis, P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)