Symmetric and asymmetric coalescence of drops on a substrate.

The coalescence of viscous drops on a substrate is studied experimentally and theoretically. We consider cases where the drops can have different contact angles, leading to a very asymmetric coalescence process. Side view experiments reveal that the "bridge" connecting the drops evolves with self-similar dynamics, providing a new perspective on the coalescence of sessile drops. We show that the universal shape of the bridge is accurately described by similarity solutions of the one-dimensional lubrication equation. Our theory predicts that, once the drops are connected on a microscopic scale, the bridge grows linearly in time with a strong dependence on the contact angles. Without any adjustable parameters, we find quantitative agreement with all experiments.

Potential additional indicators for pacemaker requirement in isolated congenital atrioventricular block.

Low heart rate is the predominantly used indication for pacemaker intervention in patients with isolated congenital atrioventricular block (CAVB). The aim of this study was to compare the difference in heart rates recorded with ECG and Holter monitoring between paced (PM) and nonpaced (NPM) patients with isolated CAVB before pacemaker implantation to identify additional predictors for future PM need. Retrospective evaluation of atrial and ventricular rates (electrocardiography) and minimal and maximal (Holter) heart rates in 129 CAVB patients prior to PM implantation (n = 93) was performed, and results are expressed in V adjusted for age and sex. The average V score for the atrial rate was 0.51 (n = 50) in the PM group and 0.60 (n = 22) in the NPM group (not-significant). The average z score for the ventricular (average) rate was -0.91 (n = 83) in the PM group and -0.93 (n = 33) in the NPM group (not-significant). Minimal heart rate was -0.94 (n = 61) in the PM group and -0.86 (n = 25) in the NPM group (not significant). Maximal heart rate was -0.96 (n = 61) in the PM group and -0.95 (n = 26) in the NPM group (not significant). Initial recordings of the average heart rate and the minimal and maximal heart rate recorded during Holter monitoring do not seem to predict future pacemaker need in patients with CAVB. Studies with exercise stress tests are needed to confirm these findings.

Combining microarrays and genetic analysis.

Gene expression can be studied at a genome-wide scale with the aid of modern microarray technologies. Expression profiling of tens to hundreds of individuals in a genetic population can reveal the consequences of genetic variation. In this paper it is argued that the design and analysis of such a study is not a matter of simply applying the existing and more-or-less standard computational tools for microarrays to a new type of experimental data. It is shown how to fully exploit the power of genetics through optimal experimental design and analysis for two major microarray technologies, cDNA two-colour arrays and Affymetrix short oligonucleotide arrays.

High and low responders to novelty and mesolimbic noradrenaline: effects of noradrenergic agents on radial-maze performance.

The authors used high and low responders to novelty (HRs and LRs, respectively) to examine the effects of noradrenergic injections into the nucleus accumbens using a special radial-maze task. During the 5 successive test days, solvent-treated HRs acquired this task faster than LRs. Isoproterenol (beta-agonist) combined with phenylephrine (alpha-agonist) improved acquisition in LRs but not in HRs; this effect was counteracted by propranolol (beta-antagonist) and phentolamine (alpha-antagonist). Propranolol combined with phentolamine, as well as phentolamine alone, disrupted acquisition in HRs but not in LRs. Data show that the effects of noradrenergic agents in HRs and LRs are due to differences in acquisition directed by type-specific differences in functional mesolimbic noradrenaline.

SKF 83959 is an antagonist of dopamine D1-like receptors in the prefrontal cortex and nucleus accumbens: a key to its antiparkinsonian effect in animals?

SKF 83959 that has a unique antiparkinson profile in animal models of Parkinson's disease is an in vitro dopamine D1 antagonist of receptors coupled to adenylyl cyclase. We hypothesized that SKF 83959, among others, interacts with dopamine D1 receptors coupled to adenylyl cyclase in the nucleus accumbens and the prefrontal cortex. Effects of intra-accumbal injections of SKF 83959 on locomotor activity were compared to effects of the dopamine D1 agonist SKF 81297 and the dopamine D1 antagonist SCH 39166. Similarly to SCH 39166, SKF 83959 did not affect locomotor activity, but counteracted SKF 81297-induced locomotor activity. Effects of unilateral intra-prefrontal injections of SKF 83959 on rotational behaviour were compared to the effects of the dopamine D1 agonist SKF 81297 and the dopamine D1 antagonists SCH 23390 and SCH 39166 in rats selected on basis of their high locomotor response to novelty and pretreated with a subcutaneous injection of 0.75 mg/kg dexamphetamine. Like SCH 39166 and SCH 23390, SKF 83959 induced a bias for contralateral rotating and blocked the SKF 81297-induced bias for ipsilateral rotating. In conclusion, SKF 83959 is an in vivo antagonist of dopamine D1 receptors that are coupled to adenylyl cyclase in the nucleus accumbens and the prefrontal cortex. The role of these receptors in the antiparkinson profile of SKF 83959 is discussed.

Suppression and recovery of estrous behavior in Syrian hamsters after changes in metabolic fuel availability.

A reduction in the availability of oxidizable metabolic fuels inhibits reproduction. Forty-eight hours of metabolic fuel deprivation inhibits estrous behavior in ovariectomized, steroid-treated Syrian hamsters, but little is known about the time course of this inhibition. Likewise, refeeding reverses deprivation-induced suppression, but the rate of recovery has not been examined. In two experiments we determined 1) the rate at which estrous behavior declines in hamsters treated with metabolic inhibitors and 2) how rapidly sexual receptivity is restored when hamsters are refed after a 48-h fast. We also measured circulating levels of leptin and insulin in an attempt to determine their relationship to the inhibition and restoration of estrous behavior. More than 24 h of metabolic inhibitor administration were required to inhibit lordosis, whereas only 6 h of refeeding were sufficient to restore the display of sexual receptivity to normal levels. Neither plasma insulin nor leptin levels paralleled the changes in estrous behavior. We concluded that 1) suppression of estrous behavior occurs more slowly than recovery after a fast and 2) changes in circulating leptin and insulin probably do not have a critical role in these behavioral changes.

Dilated cardiomyopathy in isolated congenital complete atrioventricular block: early and long-term risk in children.

OBJECTIVES: We sought to identify the risk factors predicting the development of dilated cardiomyopathy (DCM) in patients with isolated congenital complete atrioventricular block (CCAVB). BACKGROUND: Recently evidence has emerged that a subset of patients with CCAVB develop DCM. METHODS: This was a retrospective study of 149 patients with CCAVB who had heart size and left ventricular (LV) function assessed by echocardiography and chest radiography over a follow-up period of 10 +/- 7 years. RESULTS: Nine patients developed DCM at the age of 6.5 +/- 5 years. No definite cause could be identified. In these nine patients, CCAVB was diagnosed in eight at 23 +/- 2.3 weeks gestation and in one at birth. Maternal SSA/SSB antibodies were confirmed in seven of the nine patients. Pacemakers were implanted in eight patients in the first month and in one patient at five years of age. The initial left ventricular end-diastolic dimension (LVEDD) was in the 96th +/- 2.6 percentile and the cardiothoracic (CT) ratio was 64 +/- 3.8% in the nine patients who developed DCM, and differed significantly in patients with CCAVB (p < 0.005) who did not develop DCM. The LVEDD and CT ratio did not decrease in the patients with CCAVB and DCM, but decreased significantly in the patients with CCAVB without DCM (p < 0.001) once pacing was initiated. Two patients with DCM died within two months of diagnosis; one patient is neurologically compromised; two patients received a heart transplant; and four patients are listed for heart transplantation. CONCLUSIONS: Isolated CCAVB is associated with a long-term risk for the development of DCM. Risk factors may be SSA/SSB antibodies, increased heart size at initial evaluation and the absence of pacemaker-associated improvement.

Distribution of mRNAs encoding the arylhydrocarbon receptor, arylhydrocarbon receptor nuclear translocator, and arylhydrocarbon receptor nuclear translocator-2 in the rat brain and brainstem.

Dioxin exposure alters a variety of neural functions, most likely through activation of the arylhydrocarbon receptor (AhR) pathway. Many of the adverse effects, including disruption of circadian changes in hormone release and depressed appetite, seem to be mediated by hypothalamic and/or brainstem neurons. However, it is unclear whether these effects are direct or indirect, because there have been no comprehensive studies mapping the expression of components of the AhR pathway in the brain. Therefore, we used a sensitive in situ hybridization histochemical (ISHH) method to map the neural expression of AhR mRNA, as well as those of the mRNAs encoding the AhR dimerization partners, arylhydrocarbon receptor nuclear translocator (ARNT) and ARNT2. We found that AhR, ARNT, and ARNT2 mRNAs were widely distributed throughout the brain and brainstem. There was no neuroanatomic evidence that AhR is preferentially colocalized with ARNT or ARNT2. However, ARNT2, unlike ARNT expression, was relatively high in most regions. The most noteworthy regions in which we found AhR, ARNT, and ARNT2 mRNA were several hypothalamic and brainstem regions involved in the regulation of appetite and circadian rhythms, functions that are disrupted by dioxin exposure. These regions included the arcuate nucleus (Arc), ventromedial hypothalamus (VMH), paraventricular nucleus (PVN), suprachiasmatic nucleus (SCN), nucleus of the solitary tract (NTS), and the dorsal and median raphe nuclei. This neuroanatomic information provides important clues as to the sites and mechanisms underlying the previously unexplained effects of dioxins in the central nervous system.

Variation in hippocampal dynorphin b-immunoreactive mossy fiber terminal fields of apomorphine-(un)susceptible rats.

The size of distinct hippocampal sub-fields were measured in the apomorphine-susceptible and apomorphine-unsusceptible rat lines. Mossy fiber terminal fields were delineated using dynorphin B immunoreactivity and area measurements were taken from (1) the supra-pyramidal mossy fiber terminal field; (2) the intra- and infra-pyramidal mossy fiber terminal field; (3) the hilus of the fascia dentata (4) the non dynorphin B immunoreactive area of the regio inferior and fascia dentata and (5) the total area of regio inferior and fascia dentata. The data indicate that statistically significant differences in the morphometry of the hippocampal subfields of the apomorphine susceptible and unsusceptible rats are confined to the intra- and infra terminal field: the relative size of the left and right intra- and infra terminal field of apomorphine unsusceptible rats are significantly larger than those of the apomorphine susceptible rats. These data explain at least in part the differential response of these rats to novelty.

Abnormalities in liver function and coagulation profile following the Fontan procedure.

OBJECTIVE: To investigate liver function and coagulation disorders in patients with a Fontan circulation at different time intervals after surgery. DESIGN: Retrospective analysis of clinical data and cross sectional study relating liver function and coagulation profile to time since surgery, in 28 surviving patients after the modified Fontan procedure. PATIENTS: 20 patients (71%) with atriopulmonary anastomosis, seven (25%) with atrioventricular anastomosis, and one (4%) with total cavopulmonary connection. Follow up ranged from 2.0 to 21.8 years (mean 11.1). RESULTS: Abnormal liver function tests, mainly reflecting cholestasis, were present in 21 patients who had a significantly longer follow up (p < 0.01). Protein synthesis was normal in almost all patients. Coagulation profile showed abnormalities in 22 patients. "Procoagulant" abnormalities-that is, decreased plasminogen and protein C activity-were found in 11 and five patients, respectively. The extent of these abnormalities was less in patients with a longer follow up. Anticoagulant abnormalities were factor V deficiency in 16 patients and factor VII deficiency in 17, resulting in a prolonged prothrombin time in 19 patients. Thirteen patients had both pro- and anticoagulant abnormalities. A prethrombotic state was present in five patients, with a significantly longer mean time interval since surgery (p = 0.05). Thus, although the individual procoagulant indices decreased with increasing time intervals since surgery, a prethrombotic state was found particularly in patients with a long term follow up. CONCLUSIONS: Mild cholestasis was mainly present in Fontan patients with a long duration of follow up. Along with laboratory procoagulant abnormalities indicating a prethrombotic state, anticoagulant abnormalities were also present. The coagulation profile varied at different time intervals after surgery. Thus detailed evaluation should be performed regularly, and the use of anticoagulants should be considered in every patient. Long term prospective studies are needed to evaluate the individual fluctuations of coagulation profile over time following a Fontan procedure.

Changes in hypothalamic estrogen receptor-containing cell numbers in response to feed restriction in the female lamb.

The mechanism whereby undernutrition enhances the ability of estradiol (E) to inhibit reproductive activity is unknown. This study aimed to determine the effect of feed restriction on E receptor (ER)-containing cell numbers in the female sheep hypothalamus. Ovariectomized lambs at 7 months of age received either ad libitum (AL; n = 5) or restricted (FR; n = 10) levels of feed intake. Lambs were weighted weekly and FR lambs fed to lose approximately 15% of their initial body weights over 7 weeks, at the end of which jugular blood samples were collected at 10-min intervals for 5 h to assess the patterns of LH release. After blood collection, lambs were euthanized and hypothalami collected for immunocytochemical detection of ER. Based on LH secretory profiles, FR lambs were subdivided into two groups. The first group (FR + LH; n = 5) exhibited patterns of LH release similar to AL controls. LH secretion in the second group (FR-LH; n = 5) was obviously suppressed. Numbers of ER-containing cells did not differ significantly (p > 0.10) among treatment groups in the bed nucleus stria terminalis, anterior hypothalamic area and arcuate nucleus. ER-containing cell numbers were greater (p < 0.05) in the preoptic area (POA) but less (p < 0.05) in the ventromedial/ventrolateral hypothalamus (VMH/VLH) for FR-LH lambs compared to AL animals. Notably, for both the POA and VMH/VLH, ER-containing cell numbers in the FR + LH animals were intermediate and did not differ (p > 0.10) from either FR-LH or AL lambs. These results suggest that feed restriction differentially alters ER-containing cell numbers in specific regions of the ovine hypothalamus (numbers increased in the POA but decreased in the VMH/VLH). These changes may, at least in part, represent a mechanism whereby undernutrition enhances the ability of E to inhibit reproduction.

The predictive validity of the drug-naive bilaterally MPTP-treated monkey as a model of Parkinson's disease: effects of L-DOPA and the D1 agonist SKF 82958.

The aim of this study was twofold: (1) to study the predictive validity of the drug-naive, bilaterally MPTP-treated monkey as an animal model of Parkinson's disease (PD), and (2) to investigate the therapeutic and undesired effects of the D1 agonist SKF 82958 as compared to L-DOPA treatment, in drug-naive and L-DOPA pretreated monkeys. A detailed ethogram was used, allowing the separation of therapeutic and undesired effects. Eight weeks after bilateral intracarotid MPTP administration, SKF 82958 (1 mg/kg, n = 4, SKF 82958, naive group) or methyl-L-DOPA + carbi-dopa (10 + 2.5 mg/kg, n = 4, L-DOPA group) was administered intramuscularly for 22 days. After a drug-free period of eight weeks, the L-DOPA group was treated with SKF 82958 for 22 days (SKF 82959, 1 mg/kg, n=4, pretreated). All drug treatments increased the parameters used classically to evaluate dopaminergic drugs, namely body displacement, dyskinesia and dystonia. However, the new detailed analysis revealed that L-DOPA, but not SKF 82958, had therapeutic effects, reflected by an increase in goal-directed fore-limb use. SKF 82958, but not L-DOPA, induced additional undesired effects; including epileptoid behaviours in both drug-naive and drug-pretreated monkeys. In one L-DOPA-unresponsive monkey, SKF 82958 did induce minor therapeutic effects, as well as undesired effects. Although the effects of SKF 82958 on fore-limb movements, rotational behaviours and body displacement were comparable in the naive and pretreated group, SKF 82958 re-initiated undesired effects in the L-DOPA pretreated group from day one. It is concluded that the bilaterally MPTP-treated monkey is an animal model with predictive validity for PD: it adequately predicts the therapeutic effects and undesired effects of L-DOPA. Furthermore, it is concluded that SKF 82958 is less effective than L-DOPA in the treatment of PD, because it did not induce therapeutic effects, but instead elicited several undesired effects.

Temporal effects of estradiol (E) on luteinizing hormone-releasing hormone (LHRH) and LH release in castrated male sheep.

We tested the hypothesis that rapidly expressed inhibitory effects of estradiol (E) on luteinizing hormone (LH) release in the male are attributable, in part, to suppression of luteinizing hormone-releasing hormone (LHRH) release. Hypophyseal-portal cannulated, castrated male sheep were infused with E (15 ng/kg/hr) or vehicle. Portal and jugular blood samples were collected at 10-min intervals for 4 hr before, and for either 12 hr (E, n = 4; vehicle, n = 4) or 24 hr (E, n = 8; vehicle, n = 3) after the start of infusion. In animals sampled for 16 hr, temporal changes in both LHRH and LH were assessed. In animals sampled for 28 hr, only LH data were analyzed. Before either the 12-hr or 24-hr infusion, LHRH and/or LH mean concentrations, pulse amplitude and interpulse interval (IPI) did not differ between E- and vehicle-infused animals. In animals sampled for 16 hr, no effects of time or steroid x time interactions were detected for mean LHRH and LHRH pulse amplitude; however, both were greater (P < 0.01) in vehicle-infused than in E-infused males. LHRH IPI was unaffected by infusion. In contrast, both mean LH and LH pulse amplitude declined (P < 0.01) within 4-8 hr after the start of E infusion, whereas mean LH IPI was unaffected. In animals sampled for 28 hr, an effect of time (P < 0.01) and a steroid x time interaction (P < 0.01) was detected for mean LH, and there was an effect of time (P < 0.01) on LH pulse amplitude. Mean LH IPI was not affected. Our results show that in male sheep E rapidly reduces LH release in the absence of a detectable change in LHRH release.

Thyroid hormone receptor (alpha) distribution in hamster and sheep brain: colocalization in gonadotropin-releasing hormone and other identified neurons.

Thyroid hormones appear to play an important role in the seasonal reproductive transitions of a number of mammalian and avian species. These seasonal transitions as well as the effects of thyroid hormones on the reproductive neuroendocrine axis are mediated by the GnRH system. How thyroid hormones affect the GnRH system is unclear. Double label immunocytochemistry was used to examine GnRH- and other neurotransmitter/neuropeptide-containing neurons for thyroid hormone receptor (alphaTHR) colocalization in two seasonal breeders, the golden hamster and the sheep. AlphaTHR was identified in hamster and sheep brain by Western blot analysis. Furthermore, alphaTHR immunoreactivity was widely distributed in brain and was colocalized in identified populations: GnRH neurons (hamster, 28%; sheep, 46%); dopaminergic neurons of the A14 (hypothalamic) and A16 (olfactory bulb) cell groups, but not in the hypothalamic A13 cell group; and neurophysin-immunoreactive neurons of the supraoptic and paraventricular nuclei. The finding of alphaTHR in GnRH and A14 dopamine neurons provides an anatomical substrate for direct thyroid hormone action on the reproductive neuroendocrine system of these two seasonally breeding species. It remains to be determined whether the GnRH gene itself or the gene of another constituent within the same GnRH neuron is responsive to thyroid hormones.

Identification and distribution of neuroendocrine gonadotropin-releasing hormone neurons in the ewe.

The final common pathway controlling reproductive function in vertebrates is the GnRH neuron and its projection to the median eminence (ME), site of peptide release into the pituitary portal system. GnRH neurons are widely distributed; therefore we sought to test the hypothesis that those projecting to the ME are located in specific regions. We used as a model the sheep, a species in which a great deal of information regarding the physiology of GnRH secretion is known. To identify cells projecting to the ME (i.e., neuroendocrine neurons), ewes (n = 10) received injections into the ME of neuronal tract-tracing compounds: cholera toxin-beta subunit (CT-beta) or one of two fluorescent compounds (rhodamine isothiocyanate or fluorescein-conjugated dextran). Forty-eight h later, animals were perfused intracranially and their brains were processed for immunocytochemical localization of GnRH and CT-beta using a dual-immunofluorescent procedure or by single-label immunofluorescent visualization of GnRH combined with direct visualization of fluorescent tracers. Small, well-circumscribed injections into the ME were made successfully in 6 of 10 animals, and these overlapped the location of GnRH terminals and fibers. Neuroendocrine GnRH neurons (those GnRH neurons containing retrogradely transported tracer) were identified throughout their previously reported range: within the diagonal band of the Broca/medial septal region, medial preoptic area (MPOA), anterior hypothalamic area, and medial basal hypothalamus. Although the absolute number of neuroendocrine GnRH neurons varied by region, the percentage of the total GnRH population within each of these areas that was retrogradely labeled did not differ (p > 0.05). Injections placed unilaterally within the ME labeled a similar proportion of GnRH cells both ipsilateral and contralateral to the injection site in all areas except the MPOA, where ipsilaterally labeled cells were approximately twice as numerous as those labeled contralaterally. Injections that missed the ME and were placed either into the third ventricle or into the arcuate nucleus labeled only 0.5% and 4-11% of GnRH neurons, respectively. These results do not support the hypothesis that in the ewe, GnRH neurons projecting to the ME are localized to specific regions. Thus, we postulate that GnRH release into the hypophyseal portal system reflects the output of GnRH neurons located in multiple areas.

A subset of estrogen receptor-containing neurons project to the median eminence in the ewe.

The neural pathways responsible for conveying the steroid feedback signals that ultimately affect reproductive neuroendocrine function remain largely undefined. One possibility involves a direct projection from estrogen receptor (ER)-containing neurons to the median eminence (ME), a site of neuroendocrine peptide release. To examine this possibility, 8 ewes received stereotaxic injections of the retrograde neuronal tract-tracing compound cholera toxin-beta subunit (CT beta) into the ME. Neurons sending projections to the ME and containing ER were identified using a dual-label immunoperoxidase method. Double-labeled cells were found in distinct regions: (1) the ER-rich arcuate nucleus (ARC) that contained the greatest number of double-labeled cells, and (2) the organum vasculosum of the lamina terminalis (OVLT) which contained a very consistent, but low, number of double-labeled cells. While a fairly large number of retrogradely-labeled ARC neurons containing ER were identified, the majority of ER-containing ARC neurons were unlabeled and thus send projections elsewhere. Other regions containing high concentrations of ER-positive cells such as the medial preoptic area (MPOA), anterior hypothalamic area, and ventrolateral portion of the ventromedial hypothalamic nucleus, were devoid of double-labeled cells. Similarly, regions rich in neuroendocrine neurons such as the periventricular hypothalamus and paraventricular and supraoptic hypothalamic nuclei contained no double-labeled cells. These results suggest that modulation of neuroendocrine secretory activity may occur directly at the level of the ME by ER-containing neurons located within restricted regions of the hypothalamus and forebrain. However, the relatively low proportion of ER-containing neurons projecting to the ME suggests that the influence of estradiol upon neuroendocrine function also may include target sites other than the ME.

Activity of "seroquel" (ICI 204,636) in animal models for atypical properties of antipsychotics: a comparison with clozapine.

The pharmacologic treatment of schizophrenia still suffers from two major problems: (1) most antipsychotic drugs still induce severe neurologic (extrapyramidal) side effects; (2) few antipsychotic drugs are effective in treating the negative symptoms of schizophrenia. In the present study, we have evaluated the effects of ICI 204,636 in the rat paw test and the amphetamine-induced social isolation in monkeys and compared them with the effects of clozapine. The paw test has been shown to be a valid model for differentiating classic and atypical neuroleptic drugs. The monkey social isolation model seems to represent one of the few animal models with validity for the negative symptoms of schizophrenia. The results show that both ICI 204,636 and clozapine had the profile of an atypical antipsychotic in the paw test, suggesting a reduced propensity to induce extrapyramidal side effects in humans. Likewise, ICI 204,636 and clozapine were found to prevent the amphetamine-induced social isolation in monkeys, suggesting a good therapeutic effect mitigating the negative symptoms in schizophrenia. Overall, the data suggest that ICI 204,636 may represent a new and interesting antipsychotic drug, closely resembling clozapine.

Madelung deformity in skeletally immature patients: morphologic assessment using radiography, CT, and MRI.

PURPOSE: The purpose of this study was to define the pathoanatomy of the distal radius and surrounding soft tissues, identify the factors that may contribute to diminished forearm rotation, and relate these findings to alterations in wrist motion in skeletally immature patients with the Madelung deformity. METHOD: Four skeletally immature female patients with bilateral Madelung deformities (eight wrists) underwent evaluation of each wrist with radiography, CT, and MRI to assess the morphology of the deformity. Two patients (four wrists) had isolated idiopathic Madelung deformities, and two patients (four wrists) had Madelung deformities secondary to dyschondrosteosis. RESULTS: Radiographically, all wrists demonstrated dorsal bowing of the radius, marked ulnar tilting of the radius and radial tilting of the ulna, volar tilting of the distal articular surface of the radius, and triangulation of the epiphysis. On CT, patients with the idiopathic deformity demonstrated dorsal ulnar subluxation and relative supination of the carpus with respect to the distal radius. Patients with dyschondrosteosis demonstrated no ulnar subluxation and relative pronation of the carpus. All wrists demonstrated a fixed pronated deformity of the distal radius. On MRI, a physeal bar that bridged the distal metaphysis of the radius to the epiphysis was identified in all eight wrists, located on the volar aspect of the radius at the lunate facet. An anomalous volar ligament, a volar radiotriquetral ligament, and the short radiolunate ligament were hypertrophied in seven wrists. CONCLUSION: Based on its location, it is likely that a physeal bar impedes the normal development of the distal radius ulnarly. Hypertrophy of the short radiolunate ligament may be an important contributing factor to carpal pyramidalization owing to tethering on the volar pole of the lunate. Diminished forearm rotation is likely related to carpal malalignment, a fixed pronated deformity of the distal radius, and dorsal bowing of the radius.

Influence of testosterone on LHRH release, LHRH mRNA and proopiomelanocortin mRNA in male sheep.

The mechanism whereby testosterone (T) reduces pulsatile LHRH and LH release is unknown. We tested the hypothesis that hypothalamic levels of LHRH mRNA decrease and proopiomelanocortin (POMC) mRNA increase coincident with reduced LHRH release induced by either long-term or short-term T treatment in male sheep. Experiment 1 examined the effect of long-term T exposure on LHRH and LH release and LHRH and POMC mRNA levels. Yearling Suffolk rams were castrated and assigned to one of four treatments: 1) castrated (n = 4); 2) castrated, portal cannula (n = 5); 3) castrated+T (n = 4) and 4) castrated+T, portal cannula (n = 4). T-treated males received ten 10-cm silastic T-implants immediately after castration. Surgical placement of devices for collecting hypophyseal-portal blood occurred 2 to 3 months after castration. Seven to 10 days after surgery, blood samples were collected at 10-min intervals for 8 h from portal cannulated males or for 5 h from non-cannulated males to assess pulsatile LHRH and/or LH release. Immediately after blood sample collection, hypothalamic tissue was collected for in situ measurement of LHRH or POMC mRNA. T-treatment decreased (P < 0.01) mean LHRH and LH and decreased (P < 0.01) LHRH and LH pulse frequency. T did not significantly affect (P > 0.10) silver grain area per LHRH neuron, but decreased (P < 0.01) silver grain area per POMC neuron. Portal cannulation tended to decrease (P = 0.057) silver grain area per LHRH neuron without significantly affecting (P > 0.10) LHRH cell numbers while reducing (P < 0.01) silver grain area per POMC neuron and POMC cell numbers. A second experiment examined the effect of 72 h of T-infusion on LHRH and POMC mRNA levels. Castrated yearling males were assigned to receive either vehicle (n = 4) or T (768 ug/kg/day; n = 4). Blood samples were collected at 10 min intervals for 4 h prior to and during the final 4 h of infusion. Infusion of T decreased (P < 0.01) mean LH and LH pulse frequency. T did not significantly affect (P > 0.10) silver grain area per LHRH neuron or LHRH cell numbers. T reduced (P < 0.01) silver grain area per POMC neuron without affecting (P > 0.10) POMC cell number. We reject our hypothesis and conclude that reduced LHRH or heightened POMC gene expression are not mechanisms whereby T reduces pulsatile LHRH release in male sheep.

Effect of inhibiting 5 alpha-reductase activity on the ability of testosterone to inhibit luteinizing hormone release in male sheep.

The extent to which inhibitory effects of testosterone (T) on LH secretion in the ram are mediated by its metabolite dihydrotestosterone (DHT) is unknown. Our objective was to determine the effect of inhibiting 5 alpha-reductase activity on pulsatile patterns of LH release in castrated, T-treated male sheep. Nine Dorset and six Hampshire castrated male sheep were allocated equally to one of three treatment groups: 1) infusion of T (768 micrograms/kg/day), 2) infusion of the reductase inhibitor (RI) L-651,723 (0.6 mg/kg/day), and 3) T+RI infusion. Treatments were continuously infused for 3 days. Blood samples were collected via an indwelling jugular catheter at 10-min intervals for 4 h immediately prior to (Day 0) and during the final 4 h of infusion (Day 3). Changes in mean LH, LH pulse amplitude, LH interpulse interval (IPI), T, 17 beta-estradiol (E), and DHT were derived for each animal by subtracting values for Day 0 from Day 3. Data were subjected to one-way analysis of variance. The increase in T and E after infusion of T was similar (p > 0.10) in T- and T+RI-treated males and greater (p < 0.01) than in RI-treated males. The increase of DHT was greater (p < 0.01) in T-treated than either T+RI- or RI-treated males whereas the change was similar (p > 0.10) for T+RI- and RI-treated males. T decreased mean LH more (p < 0.01) than RI. T+RI suppressed mean LH more (p < 0.01) than RI but not as much (p < 0.01) as T alone.(ABSTRACT TRUNCATED AT 250 WORDS)