Shuttle-box deficits induced by chronic variable stress: reversal by imipramine administration

Escape performance in a shuttle-box task was evaluated in rats chronically exposed to a series of unpredictable stressors either during 14 or 7 consecutive days. Failure in escape responses was observed when animals were subjected to both regimes of variable aversive situations. The association between chronic exposure to unpredictable stressors with imipramine resulted in a significant reversal of escape deficits. Furthermore, animals submitted to repeated immobilization sessions during 7 days presented similar escape response to control rats. A possible involvement of beta-adrenergic sites on this behavioral response is discussed.     

Thyroid dysfunction induced by amiodarone

Amiodarone (2-n-butyl-3,4-diethylaminoethoxy-3',-diiodobenzoyl-benzofurone ) is a drug widely used for the treatment of cardiac arrhythmias. Due to its high iodine content and structural similarity to thyroxine it produces abnormalities in thyroid hormone metabolism and, in some cases, clinical thyroid dysfunction as well. We report 18 patients, 11 females and 7 males, whose thyroid disease developed during treatment with amiodarone (A). Age ranged from 13 to 64 years. A history of thyroid disease in a first-degree relative was present in five, and three patients had goiter prior to A therapy. Fifteen patients had atrial arrhythmias, and 3 had ventricular arrhythmias. Amiodarone was being given in doses of 200 to 800 mg daily. Thyroid function abnormalities appeared between 1 and 29 months after starting A therapy. Nine patients became clinically and chemically thyrotoxic; three patients developed diffuse thyroid enlargement and had total T4 concentration and FI4I increased with normal T3 and no signs of hyperthyroidism; and the six remaining patients became clinically hypothyroid with low values of total T4 and FTI and raised basal TSH. No relationship between dosages of A or duration of treatment and the appearance or severity of thyroid dysfunction was found. Regression of symptoms occurred in all but two patients with simple goiter between 1 and 8 months after amiodarone was discontinued and appropriate treatment was given. Our observations confirm the potential of A to induce thyroid abnormalities in patients with and without preexistent thyroid disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

The role of prenylamine in the prevention of adriamycin-induced cardiotoxicity. A review of experimental and clinical findings

Experimental and clinical trials to determine the potential of prenylamine in the prevention of adriamycin-related cardiotoxicity are reviewed. In mice given 4 mg/kg body weight adriamycin, the incidence of myocardial damage after 19 days' treatment was lower than in those given adriamycin and placebo. Rabbits were given adriamycin (total dose 10.8 mg/kg body weight), adriamycin plus prenylamine (1.5 mg/kg body weight), and adriamycin plus vitamins A (250 IU) and E (40 mg) for 9-11 weeks. Adriamycin-induced electrocardiogram changes were observed to a lesser extent in animals also receiving prenylamine. Heart homogenates from adriamycin-treated animals showed enhanced hydroperoxide-initiated chemiluminescence which was not affected by the simultaneous administration of prenylamine. The extent of adriamycin-induced myocytolysis and the degree of alterations observed on electron microscopy were markedly reduced by prenylamine. In a double-blind clinical trial with 26 oncological patients, no cardiomyopathy, arrhythmia or adverse reactions were observed in the group given adriamycin plus prenylamine. In those given adriamycin plus placebo, two patients developed congestive cardiopathy and another showed severe supraventricular arrhythmias together with hypotension and dyspnoea. The mechanisms of adriamycin-related cardiotoxicity, the effects of prenylamine and the benefit from combined treatment are discussed.     

A placebo-controlled, double-blind, randomized trial of cyclosporine therapy in active chronic Crohn's disease

We randomly assigned 71 patients with active chronic Crohn's disease who were resistant to or intolerant of corticosteroids to treatment with oral cyclosporine (5 to 7.5 mg per kilogram of body weight per day) or placebo for three months. Disease activity was assessed on a clinical grading scale without knowledge of the treatment given. At the end of the treatment period, 22 of the 37 cyclosporine-treated patients (59 percent) had improvement, as compared with 11 of the 34 placebo-treated patients (32 percent) (P = 0.032). During cyclosporine treatment, there was significant improvement in plasma orosomucoid levels (P = 0.0025) and the Crohn's Disease Activity Index (P = 0.00012). The effect of treatment became evident after two weeks. In the subsequent three months, during which the patients were gradually withdrawn from treatment, the improvement continued in 14 of the 37 patients (38 percent) in the cyclosporine group and in 5 of the 34 (15 percent) in the placebo group (P = 0.034). No serious adverse events were observed. We conclude that cyclosporine has a beneficial therapeutic effect in patients with active chronic Crohn's disease and resistance to or intolerance of corticosteroids.     

Opioid involvement in the adaptive change of 5-HT1 receptors induced by chronic restraint

Rats immobilized for 2 h daily for 7 days showed an increased behavioral response (forepaw treading and hind-limb abduction) to 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) 24 h after the last stress session. An injection of naloxone before each stress session fully antagonized the increased behavioral reactivity to 5-MeODMT. Treatment with morphine or beta-endorphin associated with each immobilization session for 3 days produced a response to 5-MeODMT higher than that of animals subjected to immobilization only. Chronic immobilization for 7 days did not affect the shaking behavior induced by 5-hydroxytryptophan (5-HTP) 24 h after the last restraint session. These findings suggest that chronic stress may induce a selective adaptive change of the 5-HT1 site and activate an opioid mechanism that is most likely to be involved in the development of this adaptive change.     

Inhibition of T cell mitogenesis by nitrofurans

A group of nitrofurans (5-nitro-2-furaldehyde, nifuroxime, nitrofurazone, nitrofurantoin, 5-nitro-2-furoic acid and 2-nitrofuran) were evaluated for inhibition of mitogenesis (DNA synthesis) in human peripheral blood T cells. T cells, either triggered by phorbol myristate acetate (PMA) or in the presence of accessory cells, were activated with a specified mitogen [phytohemagglutin (PHA), concanavalin A (ConA), or anti-CD3] and the amount of tritiated thymidine incorporated into DNA was determined. The results obtained indicate that nitrofurans inhibit mitogenesis irrespective of activator. 5-Nitro-2-furaldehyde was much more inhibitory than the other compounds, while 2-nitrofuran was less inhibitory. When the aldehyde group (5-nitro-2-furaldehyde) was replaced by a carboxyl group (5-nitro-2-furoic acid), the inhibitory activity was also reduced greatly. These results show that while the nitro group alone confers inhibitory activity to the furan ring, the group at the 2 position is crucial. In general, the mitogenic response of purified T cells (lacking accessory cells) triggered by PMA (phorbol ester) was inhibited less than that of the T cell-accessory cell system. With the latter, 50% inhibition of T cell mitogenesis was achieved by nifuroxime, nitrofurazone, and nitrofurantoin at 45-51 and 34-39 microM with PHA and ConA respectively. When purified T cells were used, the values were 71-85 and 55-60 microM respectively. For a given drug concentration, mitogenesis was more inhibited when induced by ConA or anti-CD3 than by PHA. The importance of using a single cell system (purified T cells) was emphasized by the interesting finding that only this system showed enhancement of mitogenesis, up to 35-40% at low drug levels. With the exception of the nitrofuraldehyde, the nitrofurans at strongly inhibitory levels were only moderately cytotoxic, exhibiting 62-85% cell survival after exposure to drug for 68 hr. Our results suggest that nitrofurans inhibit T cell mitogenesis by a relatively non-toxic mechanism; these results are comparable to those obtained for mammalian cells under aerobic conditions.     

Staged reconstruction of the severely atrophic mandible with autogenous bone graft and endosteal implants.

PURPOSE: Vastly different surgical techniques have been advocated for osseous reconstruction of the severely atrophic mandible. Endosseous implants placed in autologous bone grafts have been proposed to minimize graft resorption and restore function; however, sufficient bone must exist to support the implants and prevent pathologic fracture. The purpose of this retrospective analysis was to assess the efficacy of autologous bone grafting and the subsequent placement of endosteal implants as a staged procedure in patients with severely atrophic mandibles. MATERIALS AND METHODS: The records of all patients presenting to The University of North Carolina for treatment from 1997 to 1999 with atrophic mandibles (vertical mandibular height <7 mm as measured on panoramic radiographs in at least 1 site at the mandibular midline and at the thinnest portion of the mandibular body) were reviewed. Bone height was assessed preoperatively, immediately postoperatively, at the time of implant placement (4 to 6 months), and again at 12 and 24 months after bone grafting from posterior iliac crest to the mandible via an extraoral approach. Five endosteal implants were subsequently placed in each patient as a delayed procedure 4 to 6 months after bone grafting, and prosthetic rehabilitation was completed with implant supported prostheses. RESULTS: Fourteen consecutive patients were identified with a median preoperative bone height of 9 mm (interquartile range, 25th to 75th percentile [IQ], 7 to 10 mm) in the mandibular midline and 5 mm (IQ, 2 to 5 mm) in the body region. There were no perioperative complications. Median estimated blood loss during the bone graft procedure, as estimated by the surgeon and the anesthesiologist, was 300 mL (IQ, 150 to 1,100 mL), and 1 patient required blood transfusion secondary to symptomatic anemia. The mean loss of vertical bone height after grafting and during the 4 to 6 months before implant placement was 33%. After implant placement and at 12 months, the vertical bone loss was negligible in the implant-supported region and less than 11% in the body region. CONCLUSION: Reconstruction of the severely atrophic mandible using autogenous corticocancellous bone grafts followed by placement of osseointegrated implants in 4 to 6 months can restore and maintain mandibular bone sufficient to support implants and facilitate successful restoration of occlusion. A prospective study is planned to identify predictors of successful outcomes compared with other surgical/prosthetic treatment.     

Obstruction of the bile duct by a papillary adenoma of the gallbladder

A case of papillary adenoma of the gallbladder unassociated with cholelithiasis and showing detachment of part of the growth with obstruction of the common bile duct is described. One the basis of a search of the literature, it would appear that this is the first time such a case has been reported. The bibliography is discussed and a distinction drawn between this kind of adenoma and other benign tumors of the gallbladder.     

Pancreatic masses with inconclusive findings on spiral CT: Is there a role for MRI?

This prospective study evaluates the ability of MRI using T1-weighted fat-suppressed spin-echo (T1FS) and dynamic gadolinium chelate (Gd) enhanced spoiled-gradient echo (SGE) to detect the presence of pancreatic tumor in patients in whom spiral CT findings are inconclusive. Sixteen consecutive patients who underwent spiral CT and had findings that were considered inconclusive for pancreatic tumor underwent MR within 2 weeks of CT. Spiral CT and MR images were interpreted in a prospective fashion by separate individual investigators blinded to the results of the other imaging modality. CT was performed on a spiral CT scanner. MRI was performed on a 1.5-T MR machine. Imaging sequences included T1FS pre-Gd and post-Gd and SGE pre-Gd and immediately post-Gd. Data were analyzed using receiver operating characteristic (ROC) analysis. Confirmation was obtained by pancreatic biopsy (n = 4), surgical resection (n = 1), and clinical imaging (n = 4) or clinical follow-up (n = 7). MRI was superior to spiral CT (P = .027) in this selected patient group at detecting or excluding pancreatic tumor by ROC analysis, with areas under the curve of .982 and .764, respectively, which was significant (P = .041). The greatest advantage of MRI was in patients in whom spiral CT demonstrated enlargement of the pancreatic head without clear definition of tumor, which was significant (P = .033). In 10 patients with this CT appearance, MRI demonstrated a high confidence for presence of tumor in four and a high confidence of absence in six. Association of imaging findings with patient diagnosis was significant for MRI (P = .001) but not significant for CT (P = .148). The results of our study suggest that MRI may add significant diagnostic information in patients in whom spiral CT is inconclusive for the presence of pancreatic tumor. The greatest advantage of MRI was in the evaluation of patients in whom spiral CT findings revealed an indeterminate enlarged pancreatic head.