Evaluation of an inference-based approach to treating obsessive-compulsive disorder.

This study evaluated an inference-based approach (IBA) to the treatment of obsessive-compulsive disorder (OCD) by comparing its efficacy with a treatment based on the cognitive appraisal model (CAM) and exposure and response prevention (ERP). IBA considers initial intrusions in OCD (e.g. "Maybe the door is open", "My hands could be dirty") as idiosyncratic inferences about possible states of affairs arrived at through inductive reasoning. In IBA such primary inferences represent the starting point of obsessional doubt, and the reasoning maintaining the doubt forms the focus for therapy. This is unlike CAM, which regards appraisals of intrusions as the maintaining factors in OCD. Fifty-four OCD participants, of whom 44 completed, were randomly allocated to CAM, ERP or IBA. After 20 weeks of treatment all groups showed a significant reduction in scores on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Padua Inventory. Participants with high levels of obsessional conviction showed greater benefit from IBA than CAM. Appraisals of intrusions changed in all treatment conditions. Strength of primary inference was not correlated with symptom measures except in the case of strong obsessional conviction. Strength of primary inference correlated significantly with the Y-BOCS insight item. Treatment matching for high and low conviction levels to IBA and CAM, respectively, may optimize therapy outcome.

Time-dependent urinary bladder remodeling in the streptozotocin-induced diabetic rat model.

Urinary bladder dysfunction and remodeling are well-recognized phenomena in diabetes but detailed assessments of tissue morphological changes have not been conducted. We studied time-dependent morphological changes in bladders from diabetic rats (streptozotocin model) and evaluated the usefulness of automated digital imaging technology as an unbiased, reproducible, and convenient method for the bladder morphometric analysis. Urinary bladders were isolated from diabetic (3 days, 2 weeks or 5 weeks after single injection of streptozotocin, 65 mg/kg) or control rats (0 or 5 weeks) and were processed for histochemical evaluations (hematoxylin/eosin and Mason's trichrome staining). Digital image analysis was used to quantify equatorial cross-sectional areas of bladder tissue and lumen, as well as relative prevalence of the three primary tissue components viz. smooth muscle, urothelium, and extracellular matrix. Digital imaging and color segmentation provided reliable and unbiased evaluations of the bladder tissue sections. Progressive increases in total bladder tissue and lumen area were observed in the diabetic animals relative to controls (p<0.05), demonstrating classic hypertrophy and dilation. Prevalence of smooth muscle and urothelium (% of total tissue) both increased significantly, but collagen content decreased. Average bladder wall thickness and urothelium thickness were unchanged. Bladder remodeling during experimental diabetes is associated with time-dependent chamber dilation and increased tissue mass. Changes in bladder wall composition also occurred in a time-dependent manner, most notably increased smooth muscle and urothelium and decreased collagen prevalence. Furthermore, automated digital imaging technologies provide an unbiased, reproducible, and convenient method for detailed morphometric analysis of bladder tissues.

Perineurium inflammation and altered connexin isoform expression in a rat model of diabetes related peripheral neuropathy.

Diabetes related peripheral neuropathy involves both somatic and autonomic nerves and leads to an array of debilitating abnormalities. Mechanisms may include decreased neuronal conductance, reactive oxygen species, and decreased performance of the perineurium blood-nerve barrier. Here we studied the perineurium characteristics of the dorsal penile nerve in a rat model of diabetes related peripheral neuropathy. Immunohistochemistry showed extensive and perineurial cell-specific nitric oxide synthase2 staining in diabetic animals as compared to age matched controls (P<0.05); however no apparent difference in immunostaining pattern was observed for 3-nitrotyrosine (a stable biomarker of peroxynitrite formation). Significant reductions in connexins 32 and 26 were seen in the diabetic perineurium with no detectable levels of connexin 43 in either control or diabetic dorsal nerve. These data provide new evidence of perineurial cell inflammatory responses and altered gap junction protein expression during diabetes related neuropathies and suggests that strategies to protect this cell type may have therapeutic value.

Cysteine usage increases the need for acetate in neonates who receive total parenteral nutrition.

The addition of cysteine (as cysteine HCl) to a total parenteral nutrition (TPN) solution enhances calcium and phosphate solubility because cysteine lowers the pH of the solution. To determine whether adding cysteine to TPN solutions affected the acid-base homeostasis of infants and increased their need for acetate to obviate acidosis, we studied two groups of neonates--those receiving TPN before (group C) and after (group NC) the addition of cysteine. Measurements were made before and during the first 2 wk of TPN administration. We measured the pH of our standard TPN solution with and without the addition of cysteine. Serum carbon dioxide was significantly lower in group C despite a significantly greater intake of acetate in group NC. In the in vitro study the addition of cysteine to the TPN solution lowered the pH from 5.5 to 5.1. Newborns who received TPN solutions to which cysteine was added had lower serum carbon dioxide values and a greater need to receive acetate than did newborns who received TPN solutions without cysteine.

Use of hydrochloric acid to clear obstructed central venous catheters.

Central venous catheters are being used with increasing frequency to administer drugs, and as a result, catheter obstruction caused by precipitation of poorly soluble fluid components has become a common problem. We report our first experience using 0.1 N hydrochloric acid to restore patency to central venous catheters obstructed from insolubility-induced precipitation. Precipitation was caused by drug as well as calcium and phosphorus incompatibilities. The initial use of urokinase in two cases was unsuccessful in restoring catheter patency. In all four cases, the instillation of 0.2-1.0 ml of HCl cleared the catheters. Catheter patency usually was gained immediately. No side effects were noted. Our experience supports preliminary data (JPEN 9 (suppl):255, 1985) which suggest that 0.1 N HCl is effective in clearing insolubility-induced precipitation in central venous catheters.

Urinary excretion of Iopamidol following intrathecal administration.

No iodinated compound other than Iopamidol was found in the urine of subjects who received intrathecal injection of 10 ml of Iopamiro "300". The compound was neither metabolized nor altered in its optical configuration and urinary iodide content was always in the normal range. Between 72 and 85% of injected Iopamidol was excreted within 72 h of injection.

The reductive metabolism of the nitroaromatic flukicidal agent nitroxinil by liver microsomal cytochrome P-450.

Hepatic biotransformation of the flukicidal agent nitroxynil (3-iodo-4-hydroxy-5-nitrobenzonitrile) (I) has been studied with rat liver subcellular fractions as the source of enzymes: two metabolites, 3-iodo-4--hydroxy-5-aminobenzonitrile (II) and 3-iodo-4-hydroxy-5-nitrobenzamide (III) have been identified by standard analytical techniques (TLC, GLC and MS). The nitroaromatic reduction product (II) is formed in the hepatocyte in a process in which cytosol and endoplasmic reticulum enzymes cooperate. This formation is maximal in anaerobic conditions, but takes also place aerobically and in the absence of electrogenic cofactors. Cytochrome P-450 plays a major role in the denitrification process, and consequently could be the cellular site most exposed to damage by the intermediate arylhydroxylamine formed by reduction.

Development, chemistry, and physical properties of iopamidol and its analogues.

A series of 5-hydroxyacylamino-2,4,6-triiodo-N,N'-hydroxy-alkyl-isophtalamides was prepared in order to study the structural requirements for high water solubility and low toxicity. Among the amides substituted by 2-hydroxyethyl; 2,3-dihydroxypropyl; 1,3-dihydroxypropyl-; and 1,1-dihydroxy-methyl-2-oxyethyl- groups, the highest water solubility was obtained with the 1,3-dihydroxypropyl- group. Neither optical resolution of the 2,3-dihydroxypropyl moiety nor amide formation with two different amines improved the water solubility. The optimal solubility was obtained with S-5-alpha-hydroxypropionylamino-2,4,6-triiodoisophtalic acid di-(1,3-dihydroxy-2-propylamide), iopamidol. Iopamidol forms anhydrous and monohydrate crystals, characterized by differential thermal analyses, x-ray diffraction patterns, and solubility patterns. A method for enzymatic assay of the optical purity of iopamidol with lactodehydrogenase is described as well as partition coefficient, ionization constant of the oxyacylamido-group, critical micelle formation, surface tension, and osmolarity.

Radiopaque contrast media. XLVI - Preliminary studies of the metabolism of iopamidol in the dog, the rabbit and man.

Alter its intravenous injection in dogs and rabbits, Iopamidol was excreted almost exclusively by the kidneys. In both urine and bile, the only iodinated compound found by either TLC or HPLC was Iopamidol. Similar results were obtained after the injection of Iopamidol into the spinal subarachnoid space of rabbits. Preliminary studies in man showed that the compound was excreted unmetabolized. No racemization occurred during absorption, distribution or excretion of the contrast medium.

Radiopaque contrast media. XLIV - Preclinical studies with a new nonionic contrast agent.

L-5-alpha-hydroxypropionylamino-2,4,6-triiodoisophthalic acid di-(1,3-dihydroxy-2-propylamide), abbreviated Iopamidol, a new non-ionic water soluble contrast agent for angiography, myelography, ventriculography and for contrast reinforced computer-assisted axial tomography is described. Extensive preclinical testing showed favorable physico-chemical features of the new compound, low systemic toxicity, excellent cardiovascular and renal tolerability, very mild effects on the blood-brain barrier and on nervous tissue.

Isolation and identification of two hydroxylated metabolites of phenazopyridine in rat urine.

Together with the metabolites arised from the reductive cleavage of the azo linkage, two hydroxylated metabolites of phenazopyridine (2,6-diamino-3-[(4-hydroxyphenyl)azo]pyridine and and 2,6-diamino-3-[(2-hydroxyphenyl)azo]pyridine) were identified in rat urine, after the administration of 50 mg/kg of the drug. The structures of these metabolites were elucidated, after TLC separation, by means of I.R., N.M.R. and mass spectrometry. The presence of two hydroxylated metabolites of the intact drug support evidence that phenazopyridine is also subjected in vivo to oxidative metabolism.

[Optical resolution of N-acetyl-(R)(S)-p-methoxyphenylglycine by differential crystallization]. / Sdoppiamento ottico della N-acetil-(R)(S)-p-metossifenilglicina per cristallizzazione preferenziale

The optical resolution of the ammonium salt of N-acetyl-(R)(S)-p-metoxyphenylglycine was performed by differential crystallization producing the two enantiomeric forms with excellent optical purity. Hydrolysis with hydrochloric acid/hydrobromic acid yields the two enantiomers of p-methoxyphenylglycine and p-hydroxyphenylglycine respectively.

Radiopaque contrast media XXXI-Glucoside conjugation of iodophthalein in rabbit.

Report is given on the identification of the metabolites of the iodophthalein sodium (TIP) in rabbit. After i.v. administration two meabolites (S1 and S2) were excreted mostly in the bile, but both were also found in the urine. The TIP glucoronide (S1) is formed in much greater yield than the glucoside (S2). This latter is a further example of glucoside conjugation in mammals.