Acute toxoplasmoses in immunocompetent patients hospitalized in an intensive care unit in French Guiana.

Atypical Toxoplasma gondii strains, unrelated to archetypal clonal lineages (I, II, III), have been reported more frequently over the last decade in areas other than Europe and North America. A newly described form of toxoplasmosis, 'Amazonian toxoplasmosis' (AT), has been reported since 2002 in French Guiana. It is characterized by severe cases and atypical strains linked to a neotropical forest-based cycle. We report on the cases of AT that required intensive care management. We performed a prospective observational study on hospitalized adults in the Intensive Care Unit (ICU) from 2002 to 2008. Clinical and laboratory data, microbiological findings and outcomes were recorded. Data, including the ICU simplified acute physiology score and the pneumonia severity index, were calculated. Epidemiological risk factors for AT were assessed through questionnaires. Eleven non-immunodeficient patients were admitted to the ICU in Cayenne for life-threatening pneumonia associated with disseminated toxoplasmosis. Mechanical ventilation was necessary in seven patients, four of whom required immediate orotracheal intubation. Cardiac and ophthalmological abnormalities were found in five and four patients, respectively. One patient died from multiple organ failure. The genetic characterization of Toxoplasma DNA using six microsatellite markers revealed unique and atypical genotypes in eight patients. All patients presented epidemiological risk factors for AT. In French Guiana, significant T. gondii-related infectious syndrome associated with the lungs, a high level of LDH activity and the reported risk factors for AT was strongly suggestive of disseminated toxoplasmosis with a possible trend toward life-threatening pneumonia.

Severe acquired toxoplasmosis in immunocompetent adult patients in French Guiana.

The most common presentation of symptomatic postnatally acquired toxoplasmosis in immunocompetent patients is painless cervical adenopathy. Acute visceral manifestations are associated in rare cases. We report 16 cases of severe primary toxoplasmosis diagnosed in French Guiana during a 6.5-year period. All of the subjects were immunocompetent adults hospitalized with clinical presentations consisting of a marked, nonspecific infectious syndrome accompanied by an altered general status with at least one visceral localization, mainly pulmonary involvement (14 cases). Acute toxoplasmosis was diagnosed according to the results of serological tests suggestive of recent primary infection and the absence of an alternative etiology. Recovery was rapid following specific antitoxoplasmosis treatment. Thirteen of the 16 patients had consumed game in the 2 weeks before the onset of the symptoms, and in eight cases the game was considered to have been undercooked. Toxoplasma strains, which were virulent in mice, were isolated from three patients. Microsatellite analysis showed that all of these isolates exhibited an atypical multilocus genotype, with one allele found only for isolates of this region.

[Tuberculous meningitis in an immunocompetent adult: contribution of cerebral imaging techniques to the diagnosis and follow-up]. / Méningite tuberculeuse de l'adulte sans immunodépression acquise: contribution de l'imagerie cérébrale au diagnostic et au suivi évolutif.

We have studied 5 men, mean age 47 years, affected by tuberculous meningitis (TM) without documented immunodepression. The diagnosis of TM was supported by clinical and biological investigations and confirmed by the cultures of CSF. All the patients received a four-drug combination therapy and steroids. No drug resistance of the bacilli was observed. Cerebral imaging by CT and MRI was rarely diagnostic but most useful during the follow-up. All the patients developed complications including tuberculomas (5), hydrocephalus (4), ischemic lesions (2), arachnoiditis (1) and abscess of spinal cord (1). Four patients recovered and one died. The mean duration of the follow-up was 16 months. MRI was more sensitive than CT scan to identify inflammatory lesions such as granulomas, angeitis or arachnoiditis and to follow their outcome. Tuberculomas and hydrocephalus were easily diagnosed by CT scan with contrast enhancement. Recommendations of sequential imaging are suggested to identify unexpected or asymptomatic complications of TM during therapy and evaluate the outcome.

Rifabutin prophylaxis against Mycobacterium avium complex infections in HIV-infected patients: impact on the incidence of campylobacteriosis.

Following the observation of the decreasing occurrence of campylobacteriosis in HIV-infected patients. This study examines the incidence of campylobacteriosis in patients who had received rifabutin prophylaxis against Mycobacterium avium complex (MAC) infection compared with the incidence observed among patients treated before the advent of rifabutin. A retrospective analysis (February 1992 to November 1995) was conducted in a hospital HIV inpatient unit. The study included two patient groups: 73 HIV-infected patients with CD4 counts of < 100 cells/microL (mean 30 cells/microL) who were treated between February 1992 and July 1993 and who had not received rifabutin prophylaxis (Group R-), as well as 90 HIV-infected patients with CD4 counts of < 100 cells/microL (mean 22 cells/microL) who had received rifabutin 300 mg/day as primary prophylaxis against MAC bacteremia between July 1993 and November 1995 (Group R+). For the patient population as a whole, 20 episodes of campylobacter infection were observed in 13 patients. Causative pathogens were Campylobacter jejuni (n = 10), C. coli (8), and unidentifiable (2). Seventeen episodes (in 12 patients) of campylobacter infection occurred in Group R- versus 3 episodes (in 2 patients) in Group R+ (p < 0.0005). The rate of symptomatic infection per 100 patient-months was 0.251 in Group R+ versus 2.02 in Group R-. The results of this study indicate that rifabutin prophylaxis was associated with a decrease in the rate of campylobacter infection in HIV-infected patients. These findings are supported by evidence that rifabutin is active against C. jejuni in vitro.

The kappa agonist fedotozine relieves hypersensitivity to colonic distention in patients with irritable bowel syndrome.

BACKGROUND & AIMS: Visceral hypersensitivity plays a major role in the pathophysiology of inflammatory bowel syndrome (IBS). Opioid kappa receptors on afferent nerves may modulate it and may be the target of new IBS treatments. The aim of this study was to evaluate the effects of fedotozine, a potent and selective kappa agonist, on responses to colonic distention and colonic compliance in patients with IBS. METHODS: Fourteen patients with IBS (Rome criteria; 50 +/- 12 years; 6 men and 8 women) were included in a randomized double-blind, crossover trial comparing the effect of an intravenous infusion of 100 mg fedotozine or saline on sensory thresholds elicited by left colon phasic distention (4-mm Hg steps for 5 minutes) up to a sensation of abdominal pain. Colonic compliance was compared by the slope of the pressure-volume curves built on placebo and on fedotozine. RESULTS: In the fedotozine group, thresholds of first perception (28.7 +/- 5.9 mm Hg) and pain (34.7 +/- 5.5 mm Hg) were significantly greater than with placebo (23.3 +/- 4.5 and 29.0 +/- 3.5 mm Hg, respectively; P = 0.0078). Colonic compliance was 9. 20 +/- 3.87 mL. mm Hg-1 with placebo and 8.73 +/- 3.18 mL. mm Hg-1 with fedotozine (not significant). CONCLUSIONS: Fedotozine increases thresholds of perception of colonic distention in patients with IBS without modifying colonic compliance. Fedotozine seems capable of reversing visceral hypersensitivity observed in these patients and could have some beneficial action on their symptoms.

Effect of alosetron on responses to colonic distension in patients with irritable bowel syndrome.

BACKGROUND: Visceral hypersensitivity plays a major role in the pathophysiology of irritable bowel syndrome, as shown by balloon distension studies. 5-HT3 receptors on afferent nerves may modulate visceral sensitivity and be the target of new treatments for irritable bowel syndrome. AIM: To evaluate the effects of alosetron, a potent and selective 5-HT3 antagonist, on the perception of colonic distension by patients with irritable bowel syndrome, and on the colonic compliance to distension with a barostat. METHODS: Twenty-five irritable bowel syndrome patients were included in a randomized double-blind parallel group trial; data were available for 22 (Rome criteria; 48 +/- 11 years: 13 men and nine women). Patients were treated for 7 days with placebo (n = 6), alosetron 0.25 mg b.d. (n = 8) or alosetron 4 mg b.d. (n = 8). On day 6, a barostat bag was placed in the left colon. On day 7, after an overnight fast, isobaric phasic distensions were performed (4 mmHg steps, 5 min) up to the step triggering a sensation of abdominal pain. RESULTS: Groups were comparable at inclusion (age, sex, symptoms, bowel habits). There were no differences between treatment groups in pressure recorded within the bag at the time of first sensation of abdominal pain. However, bag volumes were significantly increased. At the first sensation threshold, median volume differences of 61 mL and 90 mL (P = 0.028) were recorded with alosetron 0.25 mg b.d. and 4 mg b.d., respectively. At the threshold of abdominal pain, these differences were 71 mL (P = 0.039) and 84 mL (P = 0.017). Colonic compliance increased from 5.9 mL/mmHg on placebo to 7.6 mL/mmHg on alosetron 0.25 mg b.d. and to 9.8 mL/mmHg (P = 0.034) on alosetron 4 mg b.d. CONCLUSION: Alosetron increases the compliance of the colon to distension, and could thereby contribute to changes in perception of colonic distension and improvement in the symptoms of irritable bowel syndrome.

Pancreatic cancer cell regulation by lipids and by basic fibroblast growth factor expression.

High fat intake is a risk factor for pancreatic cancer. Lipids may act either directly or in cooperation with growth-promoting polypeptides. In this study, the role of serum lipids, and mainly the often expressed intracellular basic fibroblast growth factor (bFGF) isoforms in cancer cells, was analyzed in pancreatic tumor cell proliferation. Serum lipids alone induced a 1.9-fold increase of human pancreatic cancer cell growth (p < 0.001). Treatment with bFGF had a weak mitogenic effect (1.2- to 1.3-fold increase) compared with those of insulin and transferrin (1.7- to 1.6-fold increase, respectively). The bFGF expression by a rat pancreatic cancer cell line that was transfected with bFGF cDNAs modified cell lipid contents and induced a higher proliferation rate than that found with the exogenous bFGF. Combined extra- and intracellular bFGFs increased cell growth by two to three times (p < 0.001), regardless the presence of extracellular lipids. The results obtained reflect the direct mitogenic effect of serum lipids and suggest that the endogenous bFGF of high molecular weight may be implicated in pancreatic cancer cell growth. By modifying cell lipids, bFGFs may interfere with other cell functions, like signal transduction.

Oxytocin increases thresholds of colonic visceral perception in patients with irritable bowel syndrome.

AIM: The effects of oxytocin on colonic perception of intraluminal distension were evaluated in 26 patients with irritable bowel syndrome (IBS), using a flaccid bag placed in the descending colon and connected to a computerised barostat. METHOD: Symptomatic responses (first sensation and pain) were evaluated during isobaric distensions (4 mm Hg increments, five minute duration, five minute interval with return to zero pressure between each step), performed automatically by the barostat, during a continuous infusion of placebo or various doses of oxytocin (10, 20, 30, and 50 mU/min). RESULTS: The distension pressure (mean (SD)) required to induce a first abdominal sensation was 17.3 (5.5) mm Hg on placebo, 19.9 (5.8) on oxytocin 10 mU/min (NS), 22.3 (6.0) mm Hg on oxytocin 20 mU/min (p < 0.01), 23.1 (6.6) mm Hg on oxytocin 30 mU/min (p < 0.01), and 24.0 (7.1) mm Hg on oxytocin 50 mU/min (p < 0.01). The distension pressure required to induce pain was 24.8 (6.3) mm Hg on placebo, 26.0 (5.8) on oxytocin 10 mU/min (NS), 33.3 (7.8) mm Hg on oxytocin 20 mU/min (p < 0.01), 34.2 (7.6) mm Hg on oxytocin 30 mU/min (p < 0.01), and 34.3 (7.9) mm Hg on oxytocin 50 mU/ min (p < 0.01). Compliance curves were not different after placebo and oxytocin injection at the different doses. Naloxone did not inhibit the effect of oxytocin. Oxytocin also did not alter somatic perception, characterised by the RIII reflex at the level of the biceps femori. CONCLUSIONS: Oxytocin significantly increases thresholds for visceral perception in IBS patients at doses equal or to greater than 20 mU/min, possibly by acting at the level of visceral afferents.

Intracolonic injection of glycerol: a model for abdominal pain in irritable bowel syndrome?

BACKGROUND & AIMS: Abdominal pain is the main symptom in patients with irritable bowel syndrome (IBS). Glycerol is an irritant of colonic mucosa. The aim of this study was to evaluate the effects of an intraluminal injection of glycerol on colonic motility and tone in patients with IBS and their modulation by drugs. METHODS: Colonic motility was evaluated using electromyography, and colonic tone was assessed using a barostat. Glycerol was injected in the right colon or the rectum. RESULTS: After intracolonic injection of glycerol, a strong abdominal colic occurred and was associated with an increase in long spike burst activity (+280%), which was eliminated by previous administration of lidocaine and was not observed after paraffin oil. When glycerol was injected intrarectally, abdominal pain occurred and long spike burst activity was increased (+240%) in the left colon. Simultaneously, colonic tone decreased (-70%) and high-amplitude phasic contractions occurred (10 +/- 1/patient). This rectocolonic reflex was reproducible in the same patient. Drugs acting on visceral afferent pathways (octreotide and granisetron) did not modify this reflex, whereas the spasmolytic drug phloroglucinol inhibited phasic contractions without affecting tone. CONCLUSIONS: Intraluminal injection of glycerol triggers viscerovisceral reflexes, resulting in abdominal pain in patients with IBS. It could be used as a model for the study of effects of drugs on pain in these patients.

Endoscopic ultrasonography in chronic pancreatitis: a comparative prospective study with conventional ultrasonography, computed tomography, and ERCP.

The usefulness and accuracy rate of endoscopic ultrasonography (EUS) in the diagnosis of chronic pancreatitis (CP) were prospectively evaluated in 81 patients with suspected pancreatic disease. All underwent EUS, abdominal ultrasonography (AUS), and computed tomography (CT), and endoscopic retrograde cholangiopancreatography (ERCP) was performed in 55 of the cases. The diagnosis of CP was established in 44 patients (CP group) including 24 with a calcified form. No pancreatic disease was observed in 18 patients (control group), and 19 patients had a pancreatic tumor. In the CP group AUS was less accurate than EUS in visualizing the pancreas, performances of CT scan being identical to EUS in this respect. A good correlation was observed between EUS and ERCP for visualization and measurement of the Wirsung duct. The most significant changes observed by EUS in the CP group were dilatation of the main pancreatic duct, heterogeneous echogenicity of the pancreatic parenchyma, and cysts < 20 mm in size even in noncalcified CP or with normal pancreatograms. Sensitivity of EUS for diagnosis of CP was 88% (AUS, 58%; ERCP, 74%; CT scan, 75%), the specificity being 100% for ERCP and EUS, 95% for CT scan, and 75% for AUS. The good performances of EUS allow early diagnosis of CP in symptomatic patients since heterogeneous echogenicity of the pancreatic parenchyma seems to be almost specifically associated with the disease.

Morphological and biological modifications induced in a rat pancreatic acinar cancer cell line (AR4-2J) by unscheduled expression of basic fibroblast growth factors.

The role of the different basic fibroblast growth factor (bFGF) forms on the regulation of pancreatic acinar cancer cells was analyzed on the rat cell line AR4-2J. This cell line expresses bFGF receptors but does not produce bFGF. AR4-2J cells were retrovirally transfected with the wild type or with point-mutated bFGF complementary DNAs in order to obtain the expression of all the bFGF forms (clone A4), or of that of the M(r) 22,500 form (clone A3), or of that of the M(r) 18,000 form (clone A5). Each clone was less tumorigenic in nude mice than AR4-2J cells. In culture, only the coexpression of all the bFGF forms modified cell morphology (fibroblast-like) and secretory enzyme synthesis (about a 20-fold decrease of amylase and lipase). Cells expressing the high molecular weight bFGF (A3 and A4) were able to grow in serum-free medium. As for AR4-2J, exogenously added bFGF still exerted mitogenic effects on the bFGF-producing cells. These results suggest that pancreatic acinar cancer cells may respond to endogenous bFGF; furthermore, they seem very sensitive to the coexpression of the different bFGF forms which is often described in cancer cells.

[Transfection of pancreatic acinar cells (AR4-2J) by bFGF modifies cell morphology and biosynthesis of pancreatic secretory enzymes]. / La transfection des cellules acineuses pancréatiques (AR4-2J) par le FGFb modifie la morphologie cellulaire et la biosynthèse des enzymes pancréatiques sécrétoires.

Basic fibroblast growth factor (bFGF or FGF-2) is present in the basal membrane of pancreatic cells during the pancreatic embryonic development. The expression of bFGF receptors has been described in normal pancreatic cells. By contrast, pancreatic cancer cells express not only the bFGF receptors but also the bFGF itself. With the aim of understanding the effects induced by the production of bFGF by pancreatic cancer cells, the pancreatic acinar cell line (AR4-2J) was used. AR4-2J cells do not produce bFGF but express bFGF receptors. These cells were transfected with a vector containing the bFGF cDNA encoding the three different forms of bFGF characterized in tumor cells. Results showed that the bFGF expression induced important phenotypic and enzymatic modifications. The transfected cells lost some morphological features of the acinar cells and expressed amylase and lipase at low levels (a 90% decrease for amylase activity, whereas lipase activity was barely detectable). These results suggest that bFGF could be involved in maintaining pancreatic cells in a slightly differentiated state.