Spondylitis in infancy. A case report

The authors report on a case of a spondylodiskitis in three year old child. Diskitis is an inflammatory process of the intervertebral disk space, not often described in pediatric age. The etiology is infective and generally presents with lumbar spine localization. Clinically it is characterized by lumbar pain at times radiating to a lower extremity. Symptoms are aspecific and radiological signs do not appear for several weeks after the onset of symptoms. Interest in this pathology derives from the fact that it may be more common than previously recognized. This case offered us the opportunity to review principal symptoms of diskitis and to describe the main diagnostic technics used.     

Perceptual and enactment measurement of self-care

The concept of self-care was conceptualized as having three major components: enabling perceptual elements (motivation, values, responsibility, and decision making); domains for enactment (cognitive/ perceptual, psychosocial/affective, and physical functioning); and self-care enactment factors (capacity), which included self-care action and knowledge adequate for self-care. A new tool, The Self-Care Agency Inventory, was designed to discriminate between those who will enact self-care and those who will not because of either a lack of knowledge or a lack of motivation. Content validity was demonstrated (.77 or greater from each scale) and concurrent validity documented. Alpha reliability for the new scale and principal components factor analysis of the scale items did not achieve desired levels, although a pilot sample demonstrated test-retest reliability of .82. The conceptual model is presented.     

Endoscopic management of biliary tract strictures in primary sclerosing cholangitis

BACKGROUND AND STUDY AIMS: In a subgroup of patients, primary sclerosing cholangitis (PSC) is complicated by high-grade focal strictures of the bile ducts, and this can have an unfavorable influence on the natural course of the disease. The aim of this study was to evaluate the efficacy and safety of endoscopic treatment in this selected patient group. PATIENTS AND METHODS: Twelve symptomatic patients with primary sclerosing cholangitis and major ductal strictures were included in a prospective study of endoscopic treatment. All patients were managed by repeated angioplasty-type balloon dilation and nasobiliary catheter perfusion. A minimum of two treatment sessions was used, and therapy was continued until satisfactory reopening of the strictures was obtained. Routine endoscopic follow-up was performed after three, six, 12, 18, and 24 months, and then at yearly intervals. The efficacy of therapy was assessed by evaluating clinical symptoms, laboratory data, and cholangiograms. RESULTS: The long-term follow-up averaged 23 months (range: 12-50 months). Two to nine (mean: three) treatment sessions were required to obtain satisfactory reopening of major biliary strictures. Eight patients showed considerable and sustained improvement. The mean serum bilirubin, alkaline phosphatase, gamma-glutamyl-transpeptidase, and alanine aminotransferase levels felt significantly by 73% (P = 0.0164), 46% (P = 0.0022), 55% (P = 0.0022), and 58% (P = 0.0022), respectively. The average radiographic stricture score before treatment was 3.2 +/- 0.8 (P = 0.0033). Three patients required liver transplantation seven, 12, and 40 months after the initiation of endoscopic treatment, due to a deterioration in hepatic function or an inability to exclude complex biliary malignancy. No major procedure-related side effects were observed. CONCLUSIONS: Our results suggest that the endoscopic treatment of PSC patients with dominant bile duct strictures is effective, safe, and well-tolerated. However, it is important not to overlook the potential development of cholangiocarcinoma.     

Sequential attachment of arginine residues to peptides, catalyzed by subtilisin. 1. Effect of organic solvent composition

Subtilisin 72 sorbed on a macroporous glass catalyzed the condensation of Dnp(or Z)-Ala2-Leu-OCH3 with arginine amide in a mixture of DMSO and acetonitrile at a water content less than 0.07% (v/v). This reaction resulted in the sequential formation of peptides containing from one to four C-terminal arginine residues. The number of attached Arg residues depended on the DMSO concentration in the solvent mixture, which determined the local arginine excess on the sorbent surface, which significantly exceeded the molar arginine excess in the solution. This enzymic reaction opened up new opportunities for preparation of peptides with different content of arginine residues.     

Myeloma cell growth arrest, apoptosis, and interleukin-6 receptor modulation induced by EB1089, a vitamin D3 derivative, alone or in association with dexamethasone

We have previously shown that malignant plasma cells expressed the specific receptor for 1,25-dihydroxyvitamin D3 and that this derivative could significantly inhibit the proliferation of such malignant cells. More recently, new vitamin D3 derivatives have been generated with extraordinarily potent inhibitory effects on leukemic cell growth in vitro. These new data prompted us to (re)investigate the capacity of such new vitamin D3 derivatives to inhibit myeloma cell growth in comparison with that of dexamethasone, a potent antitumoral agent in multiple myeloma. In the current study, we show that EB1089, a new vitamin D3 derivative, (1) induces G1 growth arrest of human myeloma cells, which is only partially reversed by interleukin-6 (IL-6); (2) induces apoptosis in synergy with dexamethasone, IL-6, leukemia-inhibitory factor, and Oncostatin M, with an agonistic anti-gp130 monoclonal antibody being unable to prevent this apoptosis; (3) downregulates both the gp80 (ie, the alpha chain of the IL-6 receptor [IL-6Ralpha]) expression on malignant plasma cells and the production of soluble IL-6Ralpha, and finally (4) inhibits the deleterious upregulation of gp80 expression induced by dexamethasone while limiting the dexamethasone-induced upregulation of gp130 expression. Considering that these in vitro effects of EB1089 have been observed at doses obtainable in vivo (without hypercalcemic effects), our present data strongly suggest that EB1089 could have a true interest in the treatment of multiple myeloma, especially in association with dexamethasone.     

Catecholamines potentiate amyloid beta-peptide neurotoxicity: involvement of oxidative stress, mitochondrial dysfunction, and perturbed calcium homeostasis

Oxidative stress and mitochondrial dysfunction are implicated in the neuronal cell death that occurs in physiological settings and in neurodegenerative disorders. In Alzheimer's disease (AD) degenerating neurons are associated with deposits of amyloid beta-peptide (A beta), and there is evidence for increased membrane lipid peroxidation and protein oxidation in the degenerating neurons. Cell culture studies have shown that A beta can disrupt calcium homeostasis and induce apoptosis in neurons by a mechanism involving oxidative stress. We now report that catecholamines (norepinephrine, epinephrine, and dopamine) increase the vulnerability of cultured hippocampal neurons to A beta toxicity. The catecholamines were effective in potentiating A beta toxicity at concentrations of 10-200 microM, with the higher concentrations (100-200 microM) themselves inducing cell death. Serotonin and acetylcholine were not neurotoxic and did not modify A beta toxicity. Levels of membrane lipid peroxidation, and cytoplasmic and mitochondrial reactive oxygen species, were increased following exposure to neurons to A beta, and catecholamines exacerbated the oxidative stress. Subtoxic concentrations of catecholamines exacerbated decreases in mitochondrial energy charge and transmembrane potential caused by A beta, and higher concentrations of catecholamines alone induced mitochondrial dysfunction. Antioxidants (vitamin E, glutathione, and propyl gallate) protected neurons against the damaging effects of A beta and catecholamines, whereas the beta-adrenergic receptor antagonist propanolol and the dopamine (D1) receptor antagonist SCH23390 were ineffective. Measurements of intracellular free Ca2+ ([Ca2+]i) showed that A beta induced a slow elevation of [Ca2+]i which was greatly enhanced in cultures cotreated with catecholamines. Collectively, these data indicate a role for catecholamines in exacerbating A beta-mediated neuronal degeneration in AD and, when taken together with previous findings, suggest roles for oxidative stress induced by catecholamines in several different neurodegenerative conditions.     

Postnatal changes in the cranial base in rabbits with congenital coronal suture synostosis

115 patients with non-immune (IgE-negative) urticaria, related to parasitic (lambliasis, oxyuriasis, ascaridiasis) or fungal (candidiasis) associations were investigated-both before and one month after specific and antihistaminic therapy-concerning different percentage levels of blood lymphocyte sets and subsets, by means of flow cytometry. Before therapy, three kinds of immune deficiency patients were obtained, one in lambliasis and oxyuriasis, the second in ascaridiasis, and the third in candidiasis, respectively. Clinical, biological and immunological recovering after therapy exhibited some differences related to the presumed non-allergic etiology, i.e. better in lambliasis and oxyuriasis and worse in ascaridiasis and candidiasis.     

Refined solution structure of 8,9-dihydro-8-(N7-guanyl)-9-hydroxyaflatoxin B1 opposite CpA in the complementary strand of an oligodeoxynucleotide duplex as determined by 1H NMR

The solution structure of d(CCATCAFBGATCC).d(GGATCAGATGG), containing the 8,9-dihydro-8-(N7-guanyl)-9-hydroxyaflatoxin B1 adduct, was refined using molecular dynamics restrained by NOE data obtained from 1H NMR. The modified guanosine was positioned opposite cytosine, while the aflatoxin moiety was positioned opposite adenosine in the complementary strand. Sequential 1H NOEs were interrupted between C5 and AFBG6, but intrastrand NOEs were traced through the aflatoxin moiety, via H6a of aflatoxin and H8 of the modified guanine. Opposite the lesion, the NOE between A16 H1' and G17 H8 was weak. A total of 43 NOEs were observed between DNA protons and aflatoxin protons. Molecular dynamics calculations restrained with 259 experimental and empirical distances, and using sp2 hybridization at AFBG6 N7, refined structures with pairwise rms differences < 0.85 A, excluding terminal base pairs. Relaxation matrix calculations yielded a sixth root rms difference between refined structures and NOE intensity data of 7.3 x 10(-2). The aflatoxin moiety intercalated on the 5'-face of the modified guanine. The extra adenine A16 was inserted between base pair AFBG6.C15 and the aflatoxin moiety. A 36 degree bending between the plane of base pair AFBG6.C15 and the plane of the aflatoxin moiety was predicted. The aflatoxin moiety stacked below the top domain of the oligodeoxynucleotide, which consisted of base pairs C1.G21, C2.G20, A3.T19, T4.A18, and C5.G17. The bottom domain consisted of base pairs AFBG6.C15, A7.T14, T8.A13, C9.G12, and C10.G11. The average winding angle between base pair C5.G17, the intercalated aflatoxin moiety, A16, and base pair AFBG6.C15 was reduced to 10 degrees. The preponderance of base pair substitutions in the aflatoxin B1 mutational spectrum, particularly G-->T transversions, suggests that the stability of this modified oligodeoxynucleotide, which models a templated +1 addition mutation, does not reliably predict the frequency of frame shifts.     

Hepatic resection in the fetal rabbit. Histologic comparison of tissue regeneration in the fetus versus the adult

Fetal tissues present peculiar features of repair after injury. Although the development of fetal hepatocytes have already been studied in vitro and in transplant models, an in vivo study of fetal liver regeneration is still missed in the literature, to the best of our knowledge. Eight time-dated pregnant California rabbits (23, 24, 25, 30 days of gestational age) and 2 adult male California rabbits were anesthetized following a standardized i.v. protocol (ketamine 50 mg/kg; xilazine 5 mg/kg; propiopromazine 0.75 mg/kg; spontaneous breathing; no anesthetic gas). All the pregnant does underwent a midline laparotomy and a minimal hysterotomy to approach a fetus per each animal. In 2 cases, 1 fetus was delivered and prior to sacrifice the fetal liver was sampled in toto (30 days of gestational age). These pregnancies were allowed to continue to term and were uneventful with a full-term spontaneous delivery of the remaining fetuses. In the other 6 pregnancies, after the hysterotomy, the fetal abdomen was entered through a right-sided longitudinal incision and the liver was partially resected by thermocauterization. Fetal abdomen was closed in 1 layer (non absorbable suture 7-0). The fetus was then returned in the uterus and, after amniotic fluid restoration with warmed saline, the hysterotomy was sutured in double layer (polyglycolic 5-0). Maternal abdomen was closed in 1 layer (polyglycolic 4-0) and the skin in a continuous overlying fashion (silk 3-0). The abdominal cavity of the 2 adult male rabbits was entered through a right subcostal incision. Partial liver resection was performed, and abdominal and skin closure followed the same techniques used for the pregnant does. The treated livers were then sampled in toto at 24, 48, 72 hrs and 4 days after surgery from the fetuses, and at 7 days from the adult rabbits. Histological stains were: H & E; Van Gieson; Masson; Alcian Bleu; PAS. Fetal histology showed a low inflammatory reaction poor in PMN cells with minimal deposition of collagen and a high amount of glycogen in the hepatocytes. The inflammatory response to resection was much more evident in the adult samples as much as the abundant intra and extra-cellular deposition of collagen associated to a minor amount of intracellular glycogen. The peculiar features of liver regeneration in the fetus, deserve further experimental studies.