Markov modelling of immunological and virological states in HIV-1 infected patients.

The purpose of this study was to evaluate the evolution of HIV infected patients and to bring out some significant factors associated with this pathology. The main criteria revealing the State of illness is viral load measurement (VL). However the CD4 lymphocytes also represent an important marker as these reflect the State of the immune reservoir. Many studies have been carried out in this field and different models have been proposed with a view to a better understanding of this disease. Multi State Markov models defined in terms of CD4 counts, or in terms of viral load, have proved to be very useful tools for modelling HIV disease progression. The model we have developed in this study is based on both the CD4 lymphocytes counts and VL. Markov models are characterized by transition intensities. In this paper we explored several structures in succession. First, we used a homogeneous continuous time Markov process with four states defined by crossed values of CD4 and VL in a given patient at a given time. Then, the effect of certain covariates on the infection process was introduced into the model via the transition intensity functions, as with a Cox regression model. Since the hypothesis of homogeneity may be unrealistic in certain cases, we also considered piecewise homogeneous Markov models. Finally, the effects of covariates and time were combined in a piecewise homogeneous model with a covariate. We applied these methods to data from 1313 HIV-infected patients included in the NADIS cohort.

[Alcohol consumption by young adults from three cities in Southern France]. / La consommation d'alcool de jeunes adultes dans trois villes du Sud de la France.

AIM: To identify potential factors of change in alcohol consumption and regional differences which could explain why and how habits are evolving. SUBJECTS AND METHODS: Four hundred and thirty three subjects aged 20 to 34 years, were recruited by random sampling in Marseilles, Montpellier and Toulouse. A quantitative food frequency questionnaire was used to collect data on alcohol consumption. A stepwise logistic regression was applied to the total sample, to the sub-sample of drinkers, and to the sub-samples of drinkers of each type of alcoholic beverage. Factors associated with each type of alcoholic consumption were analyzed by city. RESULTS: Montpellier and Toulouse samples were pooled because of the similarity in alcoholic consumption, which was different from that in Marseilles. There are significantly more drinkers in Montpellier/Toulouse than in Marseilles (74.4% versus 53.8%; p=0.001) and also more binge drinking subjects (31.1% versus 10.3%; p=0.001). Age, tobacco, leisure physical activity are independently associated with alcoholic consumption, female sex and Marseilles, being inversely associated. These two last factors are similarly associated with binge drinking, as well as age. CONCLUSION: The study of the factors for alcoholic consumption by site suggests that differences in behavior could explain these results. These distinct characteristics should be considered when implementing anti-alcoholic prevention in youth.

Development and applications of injectable poly(ortho esters) for pain control and periodontal treatment.

Poly(ortho esters) with a low glass transition temperature are semi-solid materials so that therapeutic agents can be incorporated at room temperature, without the use of solvents, by a simple mixing procedure. When molecular weights are limited to < 5 kDa, such materials are directly injectable using a needle size no larger than 22 gauge. Somewhat hydrophilic polymers can be produced by using the diketene acetal 3,9-diethylidene-2,4,8,10-tetraoxaspiro[5.5]undecane and triethylene glycol (TEG), while hydrophobic materials can be produced by using the diketene acetal and 1,10-decanediol. Molecular weight can be reproducibly controlled by using an excess of the diol, or by use of an alcohol that acts as a chain-stopper. Erosion rates can be controlled by varying the amount of latent acid incorporated into the polymer backbone. Toxicology studies using the TEG polymer have been completed and have shown that the polymer is non-toxic. Toxicology studies using the decanediol polymer are underway. Development studies using the TEG polymer aimed at providing a sustained delivery of an analgesic agent to control post-surgical pain are under development and human clinical trials using the decanediol polymer for the treatment of periodontitis are also underway.

Bioerodible injectable poly(ortho ester) for tetracycline controlled delivery to periodontal pockets: preliminary trial in humans.

The semisolid consistency of poly(ortho esters) (POEs) containing tetracycline free base allows direct injection in the periodontal pocket and shows sustained and almost constant in vitro release in phosphate buffer, pH 7.4 at 37 degrees C, for up to 14 days. Total polymer degradation concomitant with drug release was obtained. Formulations containing 10% or 20% (wt/wt) tetracycline were evaluated in a panel of 12 patients suffering from severe and recurrent periodontitis. In the first trial including 6 patients, single-rooted teeth and molar teeth with furcations were treated immediately after scaling and root planing. Patients tolerated both formulations well, experienced no pain during application, and showed no signs of irritation or discomfort during the observation period. However, retention of the formulation was minimal in this first study. An improved clinical protocol followed in the second study (stopping bleeding after scaling and root planning) prolonged the retention of the formulations in the inflamed periodontal pockets. For up to 11 days, tetracycline concentrations in the gingival crevicular fluid were higher than the minimum inhibitory concentration of tetracycline against most periodontal pathogens.

[Y-loop gastrojejunostomy in postoperative gastritis caused by reflux]. / Gastro-jéjunostomie sur anse en Y pour gastrite post-opératoire par reflux.

This prospective study involving 24 patients operated for postoperative reflux gastritis spanned over the period between 1974 and 1987. Diagnosis by exclusion was based on clinical, endoscopic and histological findings collected a few months to 16 years following surgery, the outcome of which was either alteration or destruction of the antropyloric sphincteral mechanism. All patients had Y-loop gastrojejunostomy performed according to Roux's procedure (at 50 cm). The clinical results as assessed on the basis of Visick's score and by gastroscopy were good. Anatomopathological examination of pre- and postoperative bioptic specimens blind-collected by a single operator indicated that foveolar hyperplasia is a good indicator of enterogastric reflux.

Changing patterns in the vascular form of Ehlers-Danlos syndrome.

We report and analyze two cases of Ehlers-Danlos syndrome (EDS) type 4. The first manifestation of the disease was a spontaneous perforation of the colon in a 47-year-old man; he was successfully reoperated on five years later for the rupture of an abdominal aortic aneurysm. Abdominal pain demonstrated the syndrome in a 33-year-old woman in whom multiple abdominal aneurysms were found. A ligation of the anterior tibial artery for spontaneous rupture was performed five years later. Light and electron microscopic studies of the skin disclosed similar alterations in both cases. The diameter of the collagen fiber bundles was reduced and the diameter of collagen fibrils was increased. It appears that EDS type 4 might be less characteristic than has been previously described. Classification of the different types of EDS according to electron microscopy is not possible.

[Endoscopic sclerosing for hemorrhage due to ruptured esophageal varices. Results of a prospective study of 50 cases]. / Sclérose endoscopique pour hémorragie sur rupture de varices oesophagiennes. Résultats d'une étude prospective sur 50 cas.

A prospective evaluation of sclerotherapy for bleeding esophageal varices has been conducted in 50 unselected consecutive patients. According to Child's classification, 36% were class A, 34% class B and 30% class C. Sclerotherapy was performed on an emergency basis in 22 patients and was delayed a few hours for the others. The aim of the technique was to obliterate the varices by intra- and paravariceal injections of polidocanol 1%. Injections were performed weekly for the first 3 weeks of treatment, then 3- or 6-monthly. Four patients had a severe recurrent hemorrhage during the first month. The mortality during that period was 12%. Follow-up was possible in 81% of the surviving patients. Four stenoses were treated by dilatation. Four patients had a late-recurring hemorrhage which was easily controlled in 3. Four patients died later, 3 of liver insufficiency and one of hemorrhage.

A long-term study of experimental duodenogastric reflux on the vagotomized stomach in dogs.

The possibility has been explored in dogs that the effects of chronic enteral reflux on the gastric mucosa may be modified by highly selective vagotomy (HSV). In both the innervated and the vagotomized stomachs, Roux-en-Y duodenogastrostomy induced mucosal hyperaemia and foveolar hyperplasia; the mucosa regained normal morphology after the elimination of reflux. Duodenogastrostomy without HSV did not influence basal serum gastrin but resulted in a significant increase in mucosal histamine. After duodenogastrostomy with HSV basal serum gastrin decreased significantly and mucosal histamine was not affected. It is concluded that foveolar hyperplasia is a reversible reaction of the mucosa to potentially damaging agents like enteral contents. It is also suggested that the combination of chronic enterogastric reflux, abnormal gastrointestinal motility and HSV might have an inhibitory effect on gastrin release.

Modifications of the gastric mucosal barrier induced by experimental duodenogastric reflux: an electron microscopy study.

The present study was undertaken to examine the ultrastructure of antral foveolar epithelium of dogs submitted to long term duodenogastric reflux. Minimal ultrastructural alterations (swelling of the cellular organelles, shortening of the microvilli, irregularity of the secretory granules) were observed. Total necrosis of isolated cells was rare. The lesions appeared in all dogs including the controls, and were not always reversed by the elimination of reflux. The significance of these findings is not clear and is probably not dependent on continuous exposure to duodenogastric reflux.

Endoscopic noninvasive manometry of esophageal varices: prognostic significance.

Our study attempts to establish a relation between the pressure in the esophageal varices and the clinical outcome in 18 patients in whom sclerotherapy for bleeding esophageal varices was performed. The measured pressure was compared to the endoscopic findings. Before sclerotherapy, a noninvasive manometric measurement was performed on the varices using a spheric membrane manometer fixed at the tip of an endoscope. Twelve of our 18 patients suffered repeated hemorrhage which led to death in five. We discovered a relation between the measured pressure and the outcome. Beside this, we measured the highest pressures in the largest varices. The relation that seems to exist between the pressure in the esophageal varices, the endoscopic findings, and the severity of the portal hypertension may provide new opportunities for research in this field.

[Gastroesophageal reflux: long-term results of surgical management]. / Reflux gastro-oesophagien: résultats à long terme du traitement chirurgical.

73 patients presenting with hiatus hernia and reflux oesophagitis verified endoscopically, were controlled and checked by endoscopy 5 to 15 years after surgical correction of reflux. In half of these cases the intervention consisted of a "fundoplicatio" and in the other half, of a "hemi-fundoplicatio" or closure of the angle of His. The long-term results show a higher degree of efficiency of the "fundoplicatio" particularly that which concerns the curing of the oesophagitis. The adjunction of a vagotomy-pyloroplasty in 9 patients showed an increase in the frequency of bile reflux in the stomach. The absence of cancer in the oesophagus in the 73 patients controlled after a period of many years, suggests that correction of the reflux and of the oesophagitis constitutes a high measure of efficiency.

[Treatment of refractory ascites by means of the LeVeen shunt]. / Le traitement de l'ascite réfractaire par le shunt de LeVeen.

Amongst the surgical treatments that have been suggested for refractory ascites, the one that has met with the greatest success is the LeVeen shunt. It nevertheless involves certain risks and might even be fatal. The authors' brief experience in this domain has confirmed its positive immediate effects and has also brought to light some of its drawbacks. The large number of potential complications leads one to conclude that the LeVeen shunt should be reserved for refractory ascites and hepato-renal syndrome, and should not be prematurely employed in other situations.

[Cirrhotic ascites and the renin-angiotensin system]. / Ascite cirrhotique et système rénine-angiotensine.

Plasma renin activity and plasma aldosterone have been measured in 31 patients in different clinical stages of alcoholic cirrhosis. Plasma renin activity and plasma aldosterone were within the normal range in patients with compensated cirrhosis and in patients with untreated cirrhosis and ascites. These results are not in keeping with the traditional concepts of reduced "effective' blood volume with stimulation of the renin-angiotensin system. In ascites treated with diuretics, and in the hepato-renal syndrome, the renin-angiotensin system was, however, stimulated. Peritoneo-venous shunt was followed by suppression of this stimulation.

[Anatomical study of the intramural esophageal branches of the vagus nerve with gastric distribution in man]. / Etude anatomique de branches intramurales oesophagiennes des nerfs vagues à destinée gastrique chez l'homme.

Thoraco-abdominal oseophagus was removed in continuity with the stomach during autopsy of 30 patients--two patients had undergone troncular vagotomy and pyloroplasty, the other 28 had not been operated on. In 22 cases (including the 2 which had undergone vagotomy) one or more branches of the thoracic vagus nerve existed. These branches (intramural nerves) reached the stomach after passing for 1.5 to 10 cm between the two muscular layers (of the oesophagus). They originated more often from the anterior (18) than from the posterior vagus nerve (-6). Intramural nerves are spared during abdominal vagotomy: are they the cause of some therapeutic failures of vagotomy?