Incorporation versus infection of retroperitoneal aortic grafts: MR imaging features

The magnetic resonance (MR) imaging characteristics of normal aortic graft healing were compared with those of perigraft infection in 57 patients after aortic graft implantation. Thirty-three patients without postoperative complications underwent MR imaging in a 0.35-T unit 1 week after graft implantation, and 13 of those patients were reexamined 2-3 months after graft implantation. Twenty-four patients with clinically suspected perigraft infection underwent MR imaging 6 weeks to 18 years after graft implantation. Early normal postoperative changes were characterized by a perigraft collar of low to medium signal intensity on T1-weighted images and of high intensity on T2-weighted images in all 33 cases, consistent with perigraft fluid collection. In 10 of 13 patients reexamined 2-3 months postoperatively, the MR images demonstrated a collar of tissue consistent with perigraft fibrosis. In cases of clinical suspicion of retroperitoneal graft infection, MR imaging showed eccentric fluid collections of low to medium signal intensity on T1-weighted images and high intensity on T2-weighted images at more than 3 months after surgery. The MR findings were diagnostic of retroperitoneal perigraft infection in 17 of 20 patients shown to be infected at surgery. Retroperitoneal infection was correctly excluded on the basis of MR findings in four patients. Thus, MR imaging is an accurate imaging method for the diagnosis of aortic graft infection. In the early postoperative phase, resolving perigraft fluid cannot be differentiated from perigraft infection.     

Renal impairment and gout.

A study of renal function of 51 patients with gout and an equal number of normouricaemic controls revealed significant differences. A relative impairment of the glomerular filtration rate and urine concentrating ability in the gouty subjects could not be wholly explained on the basis of aging or hypertension. Renal dysfunction was generally mild and was not associated with specific clinical characteristics higher levels of uric acid excretion, or hypertriglyceridaemia. Gout patients excreted urine with a significantly lower pH. This was associated with a relatively high excretion of titratable acid and a deficit of ammonium excretion, which was accentuated by ingestion of an acid load. Urate clearance was significantly reduced in gout, even when expressed as a fraction of the glomerular filtration rate.     

Synthesis of some [N-(2-haloalkyl)amino]tetralin derivatives as potential irreversible labels for bovine anterior pituitary D2 dopamine receptors

A series of hydroxylated 2-aminotetralins were prepared in the search for irreversible labels for D2 dopamine receptors. N-2-Haloacetyl and N-2-haloalkyl substituents were chosen as potential receptor alkylating groups. Titrimetric studies were carried out on [N-(chloroethyl)-N-methylamino]tetralins 10, 10a, 24, and 26 to demonstrate that aziridinium ions were formed as reactive intermediates from these compounds. This observation was confirmed by 1H NMR studies on compound 10. The majority of the aminotetralins prepared showed reasonably high affinity binding to anterior pituitary D2 dopamine receptors and exhibited agonist properties. Structure-activity results are presented together with preliminary studies designed to identify irreversible receptor binding agents. [N-(2-Chloroethyl)-N-propylamino]-6,7-dihydroxytetralin hydrobromide (18) proved most promising in these studies.     

Nonmedical costs to patients and their families associated with outpatient chemotherapy

One hundred thirty-nine patients receiving outpatient chemotherapy kept diaries of nonmedical expenses resulting from their disease and its treatment. Diaries were kept for both treatment and nontreatment weeks. Results showed that the mean cost to patients and their families for treatment weeks was $72.81, and for nontreatment weeks it was $45.88. Approximately 45% of these costs were out-of-pocket expenses, and 55% were wages lost. Transportation and food were the largest out-of-pocket expenses. Patients living at greater distance from treatment had higher out-of-pocket costs, and younger patients reported more wages lost. Fourteen percent of the patients were estimated to be spending more than 50% of their weekly incomes on nonmedical expenses, and these patients were found largely in the lower-income categories. A method is proposed for using these data to estimate total nonmedical expenses for different treatment regimens, and also for estimating cancer patients' total nonmedical costs nationally.     

Experimental acute tubular necrosis: US appearance

Dichromate-induced acute tubular necrosis (ATN) was created in 16 experimental animals and compared with four controls. An increase in cortical echogenicity, greatest on days 4 and 7 after injection, was noted using both histogram analysis and blinded observer readings. These findings closely correlated with proportional outer cortical blood flow. Good interobserver correlation was noted. Based on this experiment, clinical observations, and the literature, we propose that three different entities with different sonographic appearances are included under the term ATN. Drug-induced nephrotoxicity is associated with increased cortical echogenicity; ischemic ATN leads to no change in cortical echogenicity with normal medullary echogenicity; and precipitation of Tamm-Horsfall protein in the pyramids leads to echogenic pyramids with normal cortical echogenicity.     

Propofol potentiates the binding of [3H]flunitrazepam to the GABAA receptor complex.

Propofol (2,6-diisopropylphenol) robustly stimulated the binding of 1 nM [3H]flunitrazepam (FNZ) to rat brain membranes with an EC50 of 146 microM in chloride-free buffer and 23 microM in buffer containing 200 mM NaCl. NaCl showed an EC50 of 40 mM for its ability to increase the potency of propofol. The ability of a range of anions to potentiate propofol's interactions with the GABAA-benzodiazepine receptor was closely correlated with their permeabilities at this ion channel. Propofol, at a concentration of 300 microM, decreased the EC50 for the potentiation of FNZ binding by NaCl from 39 mM to 13 mM, with no change in the maximal potentiation. At a concentration of 30 microM, propofol significantly decreased the EC50 for potentiation of FNZ binding by the neurosteroid alphaxalone whilst increasing that for potentiation by pentobarbitone. We conclude that propofol is a potent barbiturate-like modulator of [3H]flunitrazepam binding.     

Bioisosteric replacement of the alpha-amino carboxylic acid functionality in 2-amino-5-phosphonopentanoic acid yields unique 3,4-diamino-3-cyclobutene-1,2-dione containing NMDA antagonists.

In this report, a novel bioisostere of the alpha-amino acid, 3,4-diamino-3-cyclobutene-1,2-dione, has been incorporated into a series of compounds which are NMDA antagonists. These compounds, which are achiral and easily prepared, demonstrated good affinity at the NMDA receptor by their ability to displace [3H]CPP binding in vitro. In particular, the phosphonic acid 24 provided protection against NMDA-induced lethality in mice equivalent to 2-amino-7-phosphonoheptanoic acid (5). This was considered an encouraging result in lieu of the fact that 24, like 5, lacks the conformational rigidity of the more potent NMDA antagonists. In addition, analogs that incorporate the 1,2,4-oxadiazolidine-3,5-dione heterocycle of quisqualic acid and the unsaturation of kainic acid were prepared to explore selectivity at the non-NMDA receptor subtypes.     

Metabolic persistence of fetal hemoglobin

Hereditary persistence of fetal hemoglobin (HPFH) has typically been ascribed to mutations in the beta-globin gene cluster. Pharmacologic agents, including the short-chain fatty acid butyrate, have been shown to upregulate fetal and embryonic globin gene expression. In this report we investigate the possibility that metabolic derangements characterized by an inability to metabolize another short-chain fatty acid, propionate, could be associated with a persistence of fetal hemoglobin unrelated to alterations in the beta-globin cluster. Embryonic globin gene upregulation in a murine adult erythroid cell culture was shown by RNase protection after induction with three short- chain fatty acids (C2-C5). Chart reviews and measurement of fetal hemoglobin in five patients with abnormalities in propionate (C3) metabolism were undertaken; SSCP/dideoxy fingerprint analysis of the gamma-globin gene promoters was done in three of these five patients. Twelve patients with other metabolic derangements served as controls. Only the four patients with clinically severe abnormalities in propionate metabolism (ages 2 to 11), but without anemia, showed a sustained elevation in fetal hemoglobin (3% to 10%). The level of elevation of fetal hemoglobin in these patients, who lack erythropoietic stress, suggests that propionic acid and/or its metabolites are potent stimulators of fetal hemoglobin expression. Study of this group of patients should allow unique insights into the long-term effects of sustained exposure to elevations of short-chain fatty acid levels.     

Acute severe deterioration in cystic fibrosis associated with influenza A virus infection.

BACKGROUND: The role of non-bacterial infection in respiratory exacerbations of cystic fibrosis has been studied less than that of bacterial infection. Some non-bacterial infections, such as influenza A, may be associated with acute respiratory deterioration and may be preventable. METHODS AND RESULTS: Three patients with cystic fibrosis showed severe deterioration in lung function and general wellbeing during the influenza A virus epidemic in the winter of 1989-90. Serological confirmation of influenza A virus infection was obtained in each case. CONCLUSIONS: As immunisation against influenza A virus is safe and provokes an adequate antibody response in patients with cystic fibrosis, it is concluded that patients with cystic fibrosis should be offered immunisation at the beginning of each influenza season. Rapid diagnostic tests and the use of antiviral drugs may have a prophylactic role in minimising lung damage.     

The value of serum IgG titres against Pseudomonas aeruginosa in the management of early pseudomonal infection in cystic fibrosis.

We report the results of a clinical trial. Patients enrolled had serum IgG titres against Pseudomonas aeruginosa above the control range. Assignment to the observation or treatment group was by minimisation. Significant signs or symptoms in any patient prompted antipseudomonal treatment. In addition, the treatment group received antipseudomonal treatment at intervals of four months until the serum IgG titre returned to the control range. P aeruginosa was isolated intermittently from patients in the main trial. Nineteen patients were enrolled (12 observation, seven treatment). After one year in the trial changes in parameters studied, including forced expiratory volume in one second, IgG titre, serum IgG concentrations, and frequency of P aeruginosa isolation had improved in the treated group and worsened in the observation group.