Oral manifestations of severe short-limb dwarfism resembling Grebe chondrodysplasia: report of a case

The oral and dental abnormalities associated with a distinct variety of severe short-limb dwarfism are described. The patient, a 9-year-old Arab boy, had delayed development and eruption of teeth, severe oligodontia of permanent dentition, hypodontia, microdontia, supplemental incisor, enamel hypoplasia of primary teeth, doubled and abnormal frenal attachments, bifid uvula, hypoplastic maxilla, and malocclusion. Clinical and radiographic examinations revealed asymmetric dysplasia and anaplasia of long bones, craniofacial dysmorphia, prominent forehead, budlike fingers and bulbous toes, dysplastic nails, severe hearing loss, and reduced joint mobility. These features resemble, in general, those characteristic of Grebe chondrodysplasia, an extremely rare ill-defined syndrome that is inherited as an autosomal-recessive disorder.     

Phenylselenenyl- and phenylthio-substituted pyrimidines as inhibitors of dihydrouracil dehydrogenase and uridine phosphorylase

Lithiation of 5-bromo-2,4-bis(benzyloxy)pyrimidine (3) with n-BuLi at -80 degrees C followed by the addition of diphenyl diselenide or diphenyl disulfide as an electrophile furnished the corresponding 5-(phenylhetera)-2,4-bis(benzyloxy)pyrimidine, which on exposure to trimethylsilyl iodide in CH2-Cl2 at room temperature yielded the 5-(phenylhetera)uracils in 70-75% yield. Similarly, the 6-(phenylhetera)uracils were prepared from 6-bromo-2,4-bis(benzyloxy)pyrimidine (10). 1-[(2-Hydroxyethoxy)methyl]-5-(phenylselenenyl)uracil (PSAU, 18) and 1-(ethoxymethyl)-5-(phenylselenenyl)uracil (17) were synthesized by the electrophilic addition of benzeneselenenyl chloride to the acyclic uracils under basic conditions. These compounds were evaluated for their ability to inhibit dihydrouracil dehydrogenase (DHUDase, E.C. 1.3.1.2), orotate phosphoribosyltransferase (OPRTase, E.C. 2.4.2.10), uridine phosphorylase (UrdPase, E.C. 2.4.2.3), and thymidine phosphorylase (dThdPase, E.C. 2.4.2.4). 5-(Phenylselenenyl)uracil (PSU, 6) and 5-(phenylthio)uracil (PTU, 7) inhibited DHUDase with apparent K(i) values of 4.8 and 5.4 microM, respectively. The corresponding 6-analogues, compounds 13 and 14, demonstrated inhibitory activity against OPRTase. PTU as well as PSU and its riboside, 2'-deoxyriboside, and acyclonucleosides were inhibitors of UrdPase, with PSAU (18) being the most potent with an apparent K(i) value of 3.8 microM. None of the compounds evaluated had any effect on dThdPase. Interestingly, most of the compounds showed modest selective anti-human-immunodeficiency-virus activity in acutely infected primary human lymphocytes.     

The sensitivity of transbronchial biopsy for the diagnosis of acute lung rejection

Transbronchial biopsy has become the procedure of choice for the diagnosis of acute lung rejection after transplantation, but the sensitivity of the technique in this setting remains unknown. In this study, 14 mongrel dogs underwent left lung transplantation, after which triple-drug immunosuppression was given for 5 days and then all immunosuppression was stopped. All animals had clear chest radiographs at this time. Transbronchial biopsy was performed in nine lung regions (two to six pieces of lung tissue were obtained per region, with a mean of 4.3 pieces per region) before the animals were killed 2 to 4 days later, at which time varying degrees of rejection had occurred. Rejection was graded histologically on a scale of 0 to 3 (0 = no rejection, 1 = mild rejection, 2 = moderate rejection, 3 = severe rejection) in each piece of lung tissue obtained at transbronchial biopsy. After the dogs were put to death, the true state of lung rejection was determined by histologic examination of the entire lung. We calculated the sensitivity of transbronchial biopsy with 95% confidence intervals. Five pieces of lung tissue were needed to yield a sensitivity of 92% (82%, 100%) to identify mild rejection in the entire lung with transbronchial biopsy. Three pieces of lung tissue were needed to yield a sensitivity of 92% (84%, 100%) to identify the presence of moderate to severe rejection in the entire lung (that is, rejection that requires pulse therapy) on transbronchial biopsy. These results indicate that three to five pieces of lung tissue that are suitable for diagnostic purposes obtained at transbronchial biopsy are adequate for the diagnosis of acute pulmonary rejection after lung transplantation.     

Cannabinoid modulation of rat pup ultrasonic vocalizations

The present study investigated the effects of the cannabinoid receptor agonist CP 55,940 (1-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl) phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol) and the cannabinoid receptor antagonist SR 141716A (N-(piperidin-l-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-me thyl-1 H-pyrazole-3-carboxamide hydrochloride) on ultrasonic vocalizations, body temperature and activity in 11-13-day-old rat pups. Testing occurred in a 5-min session 30 min following drug administration. CP 55,940 produced a dose-dependent decrease in ultrasonic vocalizations, with a 1000-micrograms/kg dose causing an almost complete inhibition of calls. Doses of 100 and 1000 micrograms/kg of CP 55,940, but not 10 micrograms/kg, caused significant hypothermia in the pups and the 1000 micrograms/kg dose also inhibited activity. The cannabinoid receptor antagonist SR 141716A (20 mg/kg) reversed the effects of 1000 micrograms/kg CP 55,940 on ultrasonic vocalizations and body temperature, but the benzodiazepine receptor antagonist flumazenil (20 mg/kg), the dopamine D1 receptor antagonist SCH 23390 (0.5 mg/kg) and the opioid receptor antagonist naloxone (1 mg/kg) did not. When administered alone, SR 141716A (20 mg/kg) increased pup ultrasonic vocalizations without affecting body temperature or activity. These results indicate that cannabinoids modulate ultrasonic vocalization production in rat pups in a manner that is independent of hypothermia. The increase in ultrasonic vocalizations produced by SR 141716A is one of the first reported behavioural effects of this drug and suggests that the endogenous cannabinoid ligand anandamide may be involved in the regulation of ultrasonic vocalizations.     

Use of absorbable mesh as an aid in abdominal wall closure in the emergent setting

A surgeon has many options available to aid in the closure of abdominal wall defects in the elective setting. In the emergent setting, active infection or contamination increases the likelihood of infection of permanent prosthetic material and limits the surgical options. In such settings, we have used absorbable mesh (Dexon) as an adjunct to fascial closure until the acute complications resolve. To evaluate the effectiveness of this technique, we reviewed the outcome of such closures in 26 critically ill patients. Between July 1987 and June 1993, 26 patients were identified who had placement of absorbable mesh as part of an emergent laparotomy at a major urban trauma center. Through a retrospective chart review, the incidence of complications and outcome of the closure were tabulated. Seven patients were initially operated on for trauma. Two of the patients had mesh placement at their initial procedure secondary to fascial loss from trauma. The remainder of the patients hd mesh placement during a subsequent laparotomy for complications related to their initial procedure. Indications for these laparotomies included combinations of wound dehiscence, intra-abdominal abscess, anastomotic disruption, and perforation. Mesh placement in patients with intra-abdominal infection created effectively open abdominal wounds that allowed continued abdominal drainage, but required extensive wound care. Despite the absorbable nature of the mesh and often prolonged hospital stay in these ill patients, none of them required reoperation for dehiscence, recurrence of intra-abdominal abscess, or infection of the mesh.(ABSTRACT TRUNCATED AT 250 WORDS)     

Low-affinity thromboxane receptor mediates proliferation in cultured vascular smooth muscle cells of rats

We examined the binding properties and mitogenic effects of U46619, using cultured vascular smooth muscle cells (VSMCs), by ligand-binding assay, measuring [3H]thymidine and [3H]leucine incorporation, checking with flow cytometry, and counting the cell number. The U46619-activated mitogenic signal-transduction pathway was assessed by measuring formation of inositol monophosphate (IP); [Ca2+]i; mitogen-activated protein kinase (MAPK), MAPK kinase (MAPKK), and p74raf-1 activities; and GTP-bound Ras. [3H]U46619 bound to cultured VSMCs from Wistar-Kyoto (WKY) rats at a single class of site (Kd: 15.5 +/- 2.6 nmol/L). However, it bound to VSMCs from spontaneously hypertensive rats (SHRs) at two classes of sites (Kd: 2.3 +/- 0.6 nmol/L and 1.4 +/- 0.5 mumol/L). U46619 increased DNA and protein synthesis, cell number, IP formation, [Ca2+]i, and MAPK and MAPKK activities, with EC50 values close to its Kd value for the low-affinity binding site in VSMCs from SHR. Prostaglandin (PG) E2 and PGF2 alpha showed little of such mitogenic effects. All these effects of U46619 were inhibited by SQ29548, staurosporine, or pretreatment of VSMCs with phorbol 12-myristate 13-acetate for 24 hours. However, U46619 stimulation did not lead to a significant increase in the Ras-GTP complex or p74raf-1 activity. In conclusion, the mitogenic effect of U46619 appears to be mediated via the activation of low-affinity thromboxane binding sites that trigger phosphoinositide hydrolysis and activate the MAPK pathway, leading to DNA synthesis and cell proliferation.     

Impact of polymers on the aggregation of wet-milled itraconazole particles and their dissolution from spray-dried nanocomposites

We explore the impact of various polymers and their molecular weight on the stabilization of wet-milled suspensions of itraconazole (ITZ), a poorly soluble drug, and its dissolution from spray-dried suspensions. To this end, ITZ suspensions with SSL, SL, and L grades of hydroxypropyl cellulose (HPC) having molecular weights (MWs) of 40, 100, and 140?kg/mol, respectively, hydroxypropyl methyl cellulose (HPMC E3 with 10?kg/mol), polyvinylpyrrolidone (PVP K30 with 50?kg/mol), sodium dodecyl sulfate (SDS, surfactant), and HPC SL–SDS were wet media milled and spray-dried. Laser diffraction results show that 2.5% HPC SL–0.2% SDS led to the finest ITZ nanosuspension, whereas without SDS, only 4.5% HPC with SL/L grades ensured minimal aggregation. Rheological characterization reveals that aggregated suspensions exhibited pronounced pseudoplasticity, whereas stable suspensions exhibited near Newtonian behavior. Spray-drying yielded nanocomposites with 60–78% mean ITZ loading and acceptable content uniformity. Severe aggregation occurred during milling/drying when 4.5% polymers with MW?≤?50?kg/mol were used; their nanocomposites exhibited incomplete redispersion due to slow matrix erosion and released ITZ slowly during dissolution test. Overall, high drug-loaded, surfactant-free ITZ nanocomposites that exhibited immediate release (>80% dissolved in 20?min) were prepared via spray-drying of wet-milled ITZ with 4.5% HPC SL/L.     

Re-operations after formerly performed suturing of the "silent" perforative duodenal ulcer

After the "silent" perforative duodenal ulcer closure the gap till the complications would occur, which need reoperation, by two times more than such period of time in patients with typical ulcer anamnesis, preceding the perforation. The reoperation causes are the recurrence (in 50.6% of observations), newly occurred ulcer (in 26.9%) or nonhealing of already existing (in 22.5%) duodenal ulcer. The reoperation method of choice is gastric resection according to Billroth-I in combination with truncal vagotomy in case of hypersecretory syndrome.