[3H]ac-RYYRWK-NH2, a novel specific radioligand for the nociceptin/orphanin FQ receptor

The hexapeptide ac-RYYRWK-NH2 has been described as a potent partial agonist at the nociceptin (NC)/orphanin FQ receptor which has no affinity for mu-, kappa- or delta-opioid receptors. However, it is not clear whether ac-RYYRWK-NH2 is truly selective for the NC receptor, and ac-RYYRWK-NH2 has therefore been radiolabelled and characterised in receptor-binding experiments. Saturation experiments with [3H]ac-RYYRWK-NH2 binding to rat cortical membranes revealed a single high affinity site for [3H]ac-RYYRWK-NH2 (Kd=0.071 +/- 0.018 nM; Bmax=22+/-2 fmol/mg protein). Uncoupling of the G-proteins resulted in a significant 45% increase in Kd and no change in Bmax. [3H]ac-RYYRWK-NH2 binding to rat cortical membranes or to membranes from baby hamster kidney cells expressing human orphan opioid receptor-like (ORL1) was displaced by NC and ac-RYYRWK-NH2 to the same extent. The following rank order of potency was observed: ac-RYYRWK-NH2 > [Tyr14]NC-OH = NC-OH = NC-NH2 > NC, H-(1-13)-NH2 > NC(1-12)-NH2 > NC(1-11)-NH2 and, thus, displayed a typical NC receptor pharmacology. Novel cyclic analogues of ac-RYYRWK-NH2 were prepared but these structures were much less active when compared to ac-RYYRWK-NH2. In vitro receptor autoradiography with [3H]ac-RYYRWK-NH2 to rat brain sections revealed high levels of binding in the cerebral cortex, amygdala, hypothalamus and superior colliculus, but low levels in the cerebellum and striatum. Overall, the regional distribution was very similar to that of [3H]NC. Ac-RYYRWK-NH2 seems indeed to be selective for the NC receptor and [3H]ac-RYYRWK-NH2 is a novel radioligand which may be useful for further exploring the pharmacology and receptor-ligand interaction of the NC receptor.     

Antinuclear antibodies in juvenile chronic arthritis.

One hundred patients with juvenile chronic arthritis (JCA) were studied with respect to granulocyte-specific and organ-nonspecific antinuclear antibodies (GS- and ON-ANA) in relation to clinical features of disease. Seventy-two were girls and 28 boys. Sixty-seven patients had IgG ANA, 31 IgM, 10 IgA, 6 IgD, 19 IgE and 35 had ANA, which fixed complement C3. Sixteen of 17 sera containing IgG GS-ANA were from girls. The prevalence of IgG GS-ANA increased with the number of joints affected. No patient with the acute febrile type of the disease had IgG GS-ANA or CS fixing ANA. The prevalence of IgG ON-ANA did not differ significantly in the mono-, pauci-, polyarticular and acute febrile types of JCA. Patients showing clinical activity more frequently had IgG and IgM ANA and C3 fixing ANA. The high titers of ANA were most often seen in girls. Chronic uveitis occurred in 10 of the patients and IgG ANA were present in sera from all of these.     

TracheobronchiaI Clearance in Twins

Tracheobronchial clearance was studied with a lest aerosol of 6μ-7μ monodisperse fluorinated ethylene propylene (Teflon 120) particles tagged with technetium 99m (half-life, 6.0 hours) and external measurements of the radioactivity in the lungs. Nine pairs of monozygotic and nine pairs of dizygotic twins were studied. The clearance patterns in the monozygotic pairs were highly similar. In the dizygotic pairs there was a tendency to similarity. Among the pairs there was a remarkable difference in the clearance patterns, Consequently the result indicates that tracheobronchial clearance to a great extent is constitutionally determined. The medical implications of this are discussed.     

Bone and joint tuberculosis in Denmark: Increase due to immigration

We studied the epidemiology of bone and joint tuberculosis (TB) in Denmark during the period 1993-1997, using data in the national Danish TB register. We found 95 cases, accounting for 4% of all tuberculosis cases and 15% of extrapulmonary cases, giving a mean annual incidence of 0.4 per 10 5 in the period. 26 cases were found among native Danes (3-8 cases per year) with a median age of 66 (10-92) years and giving a mean annual incidence of 0.1 per 10 5 . Among immigrants, an increasing number of cases of bone and joint TB were diagnosed, increasing from 5 in 1993 to 28 in 1997, giving a total of 69 cases with a mean age of 35 (11-75) years and a mean annual incidence of 4 per 10 5 in the period. The spine was affected in half of the cases. 28 patients had active TB elsewhere in the same period. In most patients, there were no predisposing or risk factors for disease except for ethnicity. Compared to a study of bone and joint TB in Denmark in the 1980s, the total incidence is the same, but there has been a shift in patients from old Danes to young immigrants. The increasing number of bone and joint TB cases among immigrants is due to recent immigration of Somalian refugees, who have a high incidence of TB and a high proportion of extrapulmonary TB. The diagnosis was often delayed several months or years. This study shows that attention must be paid to this condition, particularly in young patients from an endemic immigrant population.     

The quantitative genetics of sex differences in parenting

Sex differences in parenting are common in species where both males and females provide care. Although there is a considerable body of game and optimality theory for why the sexes should differ in parental care, genetics can also play a role, and no study has examined how genetic influences might influence differences in parenting. We investigated the extent that genetic variation influenced differences in parenting, whether the evolution of differences could be constrained by shared genetic influences, and how sex-specific patterns of genetic variation underlying parental care might dictate which behaviors are free to evolve in the burying beetle Nicrophorus vespilloides. Females provided more direct care than males but did not differ in levels of indirect care or the number of offspring they were willing to rear. We found low to moderate levels of heritability and evolvability for all 3 parenting traits in both sexes. Intralocus sexual conflict was indicated by moderately strong intersex genetic correlations, but these were not so strong as to represent an absolute constraint to the evolution of sexual dimorphism in care behavior. Instead, the pattern of genetic correlations between parental behaviors showed sex-specific tradeoffs. Thus, differences in the genetic correlations between parental traits within a sex create sex-specific lines of least evolutionary resistance, which in turn produce the specific patterns of sex differences in parental care. Our results therefore suggest a mechanism for the evolution of behavioral specialization during biparental care if uniparental and biparental care behaviors share the same genetic influences.     

Use of the Intubating LMA-Fastrach™ in 254 Patients with Difficult-to-manage Airways

Background : The laryngeal mask airway (LMA(TM); LMA North America, Inc., San Diego, CA) has a well-established role in the emergency and elective treatment of patients with difficult-to-manage airways (DA). In this study, the authors report their clinical experience with the intubating LMA (LMA-Fastrach(TM); LMA North America, Inc., San Diego, CA) in 254 patients with different types of DA.

Methods : The authors reviewed the anesthetic and medical records of patients with DA in whom the LMA-Fastrach(TM) was used electively or emergently at four institutions from October 1997 through October 2000. In each case, the number of insertion and intubation attempts was recorded. Success rates for blind and fiberoptically guided intubation through the LMA-Fastrach(TM) were calculated, up to a maximum of five attempts per patient.

Results : The LMA-Fastrach(TM) was used in 257 procedures performed in 254 patients with DA, including patients with Cormack-Lehane grade 4 views; patients with immobilized cervical spines; patients with airways distorted by tumors, surgery, or radiation therapy; and patients wearing stereotactic frames. Insertion of the LMA-Fastrach(TM) was accomplished in three attempts or fewer in all patients. The overall success rates for blind and fiberoptically guided intubations through the LMA-Fastrach(TM) were 96.5% and 100.0%, respectively.     

Early urinary changes in Tamm-Horsfall protein and epidermal growth factor in diabetic children

Both glomerular and tubular markers have been used to follow diabetic nephropathy. However, neither albumin nor proximal tubular markers have proven useful in prepubertal diabetes. Hence we studied two markers derived from the distal tubular cells, Tamm-Horsfall protein (THP) and epidermal growth factor (EGF). The urinary excretion of THP and EGF was examined in samples obtained during the first 20 days and 1 year after diagnosis of diabetes in children aged 4–15 years. Fourteen children without and 18 with ketonuria were examined, and 17 age-matched healthy children participated as controls. The excretion rate of EGF was increased at diagnosis, while that of THP was not. After 20 days of treatment the excretion of EGF had normalized, while the excretion of THP was decreased. Similar results were obtained after 1 year. In conclusion, in spite of good metabolic control a reduced excretion of THP persisted for at least 1 year after the diagnosis of diabetes. Whether the finding of reduced excretion of THP has any biological significance awaits further study. Received: 21 July 2000 / Revised: 16 January 2001 / Accepted: 17 January 2001     

Neutrophil adhesion molecules in colorectal surgery: effect of filgrastim given perioperatively.

OBJECTIVE: To assess whether the postoperative expression of neutrophil adhesion molecules CD11b/CD18 (Mac-1) and CD62L (L-selectin) would differ in peripheral blood, peritoneal fluid and wound fluid in patients operated on for colorectal conditions, and to analyse the effect of perioperative filgrastim on their expression. DESIGN: Prospective randomised double-blind placebo-controlled clinical study. SETTING: University hospital, Finland. SUBJECTS: Thirty consecutive patients undergoing elective colorectal operations (15 in each group). INTERVENTIONS: The patients were prospectively randomised to receive either filgrastim or placebo. Expression of neutrophil adhesion molecules was measured 48 hours postoperatively in peripheral blood, peritoneal fluid, and wound fluid by flow cytometry. RESULTS: Postoperative neutrophil CD11b/CD18 expression was higher in both wound fluid and peritoneal fluid than in peripheral blood in the placebo group. Simultaneously, the expression of neutrophil CD62L was higher in peripheral blood than in peritoneal fluid or wound fluid in both groups. Filgrastim caused increased postoperative expression of neutrophil CD11b/CD18 in peripheral blood but not in peritoneal fluid or wound fluid. CONCLUSIONS: Postoperative expression of neutrophil adhesion molecules differs at the local operation site from that in peripheral blood. Filgrastim increases only blood neutrophil CD11b/CD18 expression.