Use of proline bioisosteres in potential HIV protease inhibitors: phenylalanine-2-thiophenoxy-3-pyrrolidinone: synthesis and anti-HIV evaluation.

The synthesis of new phenylalanine-2-thiophenoxy-3-pyrrolidinones is described. Anti-HIV recombinant protease assays and HIV infected cell culture assays (observation of syncytia) demonstrated the potent anti-HIV activity of this new class of pseudopeptides.

Tri-N-Boc-tetraazamacrocycle-nucleoside conjugates: synthesis and anti-HIV activities.

As far as linear N-Boc-polyamines conjugates elicited remarkable anti-HIV activity, the synthesis and anti-HIV properties of cyclic N-Boc-polyamines conjugates such as tetraazamacrocycle-nucleoside were studied. These new conjugates include an ester linkage between the two moieties. They were synthesized using Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate coupling reagent, in the case of N-alkyl polyazamacrocycle derivatives, or through direct condensation of the acyl chloride derivative with nucleoside in the case of N-acyl polyazamacrocycle compounds. None of the new conjugates presented anti-HIV activity greater than that of the corresponding parent nucleosides.

Synthesis and anti-HIV activities of symmetrical N1,N3-dibenzyl-2-hydroxy-propane derivatives.

We report the synthesis and the anti-HIV activities of new C2-symmetrical and achiral N1,N3-dibenzyl-2-hydroxy-propane isosteres. Some of them showed significant inhibitory activity with respect to HIV-infected MT4 cells (compound 6a and 7a, IC50 = 0.1 microM). These new structurally simple compounds represent new synthons which can be suitable for combinatorial chemistry purposes.

Syntheses of new modified Phe-Pro peptides. Use of proline replacements in potential HIV inhibitors.

The syntheses consisting of replacement of proline amino acid by a 3-pyrrolidinone ring in Phe-Pro analogues are described. Preliminary anti-HIV studies demonstrated the potential activity of this new class of compounds.

Selective inhibition of the duck hepatitis B virus by a new class of tetraazamacrocycles.

The antiviral activity of a new class of N,N,N',N",NA'''-pentakis (omega-aminoalkyl) tetraazamacrocycles was evaluated in primary duck hepatocyte cultures infected with the duck hepatitis B virus (DHBV). Three of the four tested compounds were able to selectively inhibit DHBV replication by acting at an early step of the hepadnavirus infection but were associated with significant toxicity.

[Evaluation of the teaching of echo-endoscopy. Application to the assessment of invasiveness of cancer of the esophagus and the cardia]. / Evaluation de l'enseignement de l'écho-endoscopie. Application au Application au bilan d'extension du cancer de l'oesophage et du cardia.

OBJECTIVES: Learning endosonography (EES) is known to be difficult, and the theory must be understood before performing EES routinely. The aim of the study was to evaluate the diagnostic indexes of EES in the staging of cardio-oesophageal cancer after a period of theoretical apprenticeship of EES and a learning period in a centre experienced in EES since 1989. METHODS: Five observers, having never used EES, followed to EES examinations for a 3-6 month period. They then reviewed the standardized records of 29 patients with cardio-oesophageal cancer. They had to evaluate the degree of tumour infiltration within oesophageal wall and the site of metastatic lymph nodes. Results were compared with the diagnosis of 5 experienced senior endoscopists. Interobserver agreement was estimated with kappa statistics and considered excellent for k > or = 0.75, good to moderate if 0.75 > k > or = 0.40, and poor if k < 0.40. RESULTS: Inter-observer agreement was poor for the topographic diagnosis of lymph nodes (kappa index from -0.09 to 0.33), lower to that of the 5 senior observers (0.33 to 0.77). It was satisfactory for degree of tumour infiltration (T1: k = 0.66; T2: k = 0.58; T3: k = 0.56; T4: k = 0.46). The individual sensitivities were weak according to lymph nodes site, but good for presence of lymph nodes (86 to 100%), with a specificity of 40 to 73%. CONCLUSIONS: After theoretical training of EES, agreement and diagnostic performances are good enough to diagnose pathological images (except for T4 tumors), and poor for localizing images in the mediastinum. This emphasizes the difficulties in learning echo-anatomy and gives useful guidelines for training programs in EES.

[Severe gastroduodenal ulcer hemorrhage. Treatment with endoscopic injections of an epinephrine solution]. / Hémorragies ulcéreuses gastroduodénales graves. Traitement par injections endoscopiques d'une solution d'épinéphrine.

Eighty-three patients (more than one half of whom were at high surgical risk) presenting with haemorrhages from a gastric or duodenal ulcer were treated with endoscopic injections of an epinephrine-hypertonic saline mixture. The overall rate of definitive haemostasis was 83 p. 100. Depending on the degree of haemorrhagic activity, this rate was 64 p. 100 in pulsatile lesions, 90.5 p. 100 in oozing lesions, 85.7 p. 100 in cases with visible vessels and 81.2 p. 100 when signs of recent bleeding were present. There was no dangerous complication related to the technique. The overall survival rate was 67.5 p. 100 and 20 out of the 26 deaths were due to other causes than haemorrhages. On follow-up, 94.7 p. 100 of the ulcers healed under antisecretory treatment within the usual length of time. This simple, effective and inexpensive technique is suggested as initial treatment of gastric or duodenal haemorrhages in subjects at high surgical risk, especially since the haemorrhage has no influence on the course of the ulcer.

[Endoscopic treatment of severe digestive hemorrhage by hemostatic injection]. / Traitement endoscopique des hémorragies digestives graves par injection hémostatique.

The results of emergency endoscopic treatment of severe non variceal bleeding in the upper and lower gastrointestinal tract by hemostatic injections are reported. Most of the 44 patients were seriously ill and had a high surgical risk. Definitive hemostasis was obtained in 88.6 per cent of cases. Twenty-five patients had active bleeding which was arrested in 84 per cent of cases. There were no serious complications related to the technique. The overall survival rate was 52 per cent. Ten of the 13 deaths were not due to gastrointestinal hemorrhage. The authors advocate this simple, effective and inexpensive method as the initial treatment of ulcerated gastrointestinal bleeding in critically ill patients.

[Acute hepatitis caused by isaxonine phosphate (Nerfactor)]. / Hépatite aiguë due au phosphate d'isaxonine (Nerfactor).

We report the cases of four adult patients suffering from acute hepatitis due to isaxonine phosphate (Nerfactor), a drug recently proposed for the treatment of the lesions of peripheral nerves. Hepatitis developed 14 to 166 days after the beginning of the administration of the drug. In all the patients, predominantly centrilobular hepatocytic necrosis was present. In two of our patients, the course of hepatitis was fatal. Hepatitis induced by isaxonine phosphate is likely to be due to an immuno-allergic mechanism.

Propranolol in prevention of recurrent gastrointestinal bleeding in cirrhotic patients.

Placebo or propranolol was given randomly of two groups of 12 adults with cirrhosis who had recently held from oesophageal or gastric varices or from acute gastric erosions. During three months' follow-up 5 patients in the placebo and none in the propranolol group had recurrent gastrointestinal bleeding.

[Treatment and outcome of severe ulcerative colitis with mucosal undermining on X-rays (author's transl)]. / Traitement et évolution des formes graves de rectocolite hémorragique avec décollements muqueux.

The authors present a retrospective study of 11 patients who had suffered from a severe attack of ulcerative colitis with extensive undermining of the mucosa on barium enema. All patients were given corticosteroids and antibodies. Oral feeding was suspended in 7, and 3 received exclusive parenteral nutrition. In 2 cases medical treatment resulted in complete remission, but 9 patients underwent surgery (total proctocolectomy in 4, total colectomy with ileo-rectal anastomosis in 3, colostomy in 1 and exploratory laparotomy in 1). Six of the operated patients were followed up for 1 to 7 years and are now in good health; the remaining three died early in the post-operative period. Extensive mucosal undermining in ulcerative colitis is a factor of poor prognosis.