Determinants of radiological patterns and severity in immunocompromised adults with Metapneumovirus infection.

BACKGROUND: Human Metapneumovirus (HMPV) belongs to the Pneumoviridae family and is responsible for respiratory infections. Mild infections are well-recognized in children, while its precise impact in various categories of immunocompromised adults has not been well addressed. RESEARCH QUESTION: We retrospectively studied HMPV infections in immunocompromised adults followed in two large French university medical centers. STUDY DESIGN AND METHODS: We identified immunocompromised adults with positive HMPV Polymerase Chain Reaction (PCR) for 36 months and reviewed their medical charts. For lung transplant recipients (LTR), FEV1 was collected at baseline, during and after infection. Imaging was centralized and chest involvement was categorized by dominant CT patterns. We compared severe patients (requiring oxygen or ventilation) and non hypoxemic patients. RESULTS: Seventy-two patients were included, 27 were LTR, 25 had a hematological malignancy or were hematopoietic stem cell recipients, 20 had another immunocompromised status. Twenty patients (28%) presented a hypoxemic infection, requiring hospitalization and intensive care units transfers in 50/72 (69.4%) and 9/72 (12.5%) respectively, with only one death. Hypoxemia was less pronounced in LTRs (p = 0.014). Finally, age and dyspnea remained independent factors associated with hypoxemia (p < 0.005). The most frequent radiological patterns were bronchopneumonia (34.2%) and bronchiolitis (39.5% and 64.3% in the overall population and in LTRs respectively, p = 0.045). FEV1 improved in LTRs at one month and 85% had recovered their baseline FEV1 within 6 months. INTERPRETATIONS: In immunocompromised adults, HMPV infections required frequent hospitalizations and ICU transfers, while mortality is low. In LTRs, bronchiolitis pattern was predominant with short and long-term favorable outcome.

[Pulmonary histoplasmosis in an immunocompetent patient]. / Histoplasmose pulmonaire chez un patient immunocompétent avec nodules pulmonaires multiples évoluant vers la nécrose.

INTRODUCTION: Acute pulmonary histoplasmosis (APH) is rare in an immunocompetent patient. We report a case of APH diagnosed by culture of broncho-alveolar lavage (BAL) in a patient presenting a pseudo-tumoral form with nodules progressing to cavitation. OBSERVATION: A 41 year-old male smoker was hospitalized with a persistent fever, dry cough and dyspnoea on exertion. The first CT scan showed a reticulo-nodular interstitial infiltrate with lymphadenopathy that progressed rapidly to multiple pulmonary nodules with central cavitation. Bronchial endoscopy, with BAL culture, provided the diagnosis of Histoplasma capsulatum, variety capsulatum. The infection may have occurred during work in a hangar in Guadeloupe that was scattered with bats' guano. After two months of treatment by itraconazole, the patient's condition improved clinically and radiologically with reduction of the nodules and their cavitation. CONCLUSION: This case presents an immunocompetent patient with pulmonary histoplasmosis and multiple, radiologically atypical, nodules. The diagnosis was established by BAL culture.

Mouse cerebral magnetic resonance imaging fails to visualize brain volume changes after experimental subarachnoid hemorrhage.

BACKGROUND: Brain atrophy after subarachnoid hemorrhage (SAH) has been detected in humans and might serve as a functional read-out parameter for neuropsychological deficits. To determine whether serial magnetic resonance imaging (MRI) can provide information on brain atrophy in animals as well, mice that had undergone experimental SAH were scanned repeatedly after the bleeding. METHODS: Using a 7-T rodent MRI, six mice were evaluated for total hemispheric, cerebrospinal fluid (CSF) and hippocampal volumes on days 1, 2, 4, 21, 28, 42 and 60 after experimental SAH or sham operation, respectively. RESULTS: Repeated MRI scanning demonstrated a very high reproducibility with minimum standard deviation. Nevertheless, no significant differences were found between the two groups concerning hemispherical volumes or hippocampal volumes. A transient but significant increase in CSF volume was detected on days 2 and 60 after SAH. Compared with the existing method, no MRI data on brain atrophy in mice after experimental SAH have been published. CONCLUSION: Repeated brain MRI in mice after experimental SAH did not provide additional information on brain atrophy. Our data suggest that this is not due to a lack of sensitivity of the method. Despite all promising details about MRI, our results should initiate careful consideration (additional sequences/other questions) before its further use in this certain area, especially since it is expensive and associated with demanding logistics.

[Incidence of sarcoidosis in Guadeloupe. A 13-year retrospective study: 1997-2009]. / Incidence de la sarcoïdose en Guadeloupe: étude rétrospective sur 13 ans (1997-2009).

INTRODUCTION: Sarcoidosis is a systemic granulomatosis of unknown origin with a high incidence in the Afro-American population. There is no epidemiologic data regarding Afro-Caribbean population. The aim of our study was to evaluate the incidence and epidemiologic data of the disease, on the island of Guadeloupe, (French West Indies; 402 500 inhabitants, 90% Afro-Caribbean people) during the 13-years period between 1/01/1997 and 31/12/2009. METHOD: We performed a retrospective study including exclusively patients with a diagnosis of sarcoidosis confirmed by histological examination of the involved tissues. RESULTS: One hundred and thirteen patients were enrolled in the study. One hundred and eleven patients (98%) were black Caribbean of African European descent. Eighteen patients (16%) were more than 65 years old. The crude annual incidence over the study period was 2.9 cases per 100,000 inhabitants (IC 95%: [2,4-3,4]). The main localization of the disease was the chest (89%). Radiographic stages were distributed as following: I (31%), II (39%), III (15%), IV (2%). CONCLUSION: Our study showed a low incidence rate of sarcoidosis on the island of Guadeloupe over the study period with a high rate of old patients.

Agonist actions of dihydroergotamine at 5-HT2B and 5-HT2C receptors and their possible relevance to antimigraine efficacy.

1. The pharmaceutical compound, dihydroergotamine (DHE) is dispensed to prevent and reduce the occurrence of migraine attacks. Although still controversial, the prophylactic effect of this drug is believed to be caused through blockade and/or activation of numerous receptors including serotonin (5-HT) receptors of the 5-HT2 subtype. 2. To elucidate if 5-HT2 receptors (5-HT2Rs) may be involved in DHE prophylactic effect, we performed investigations aimed to determine the respective pharmacological profile of DHE and of its major metabolite 8'-hydroxy-DHE (8'-OH-DHE) at the 5-HT2B and 5-HT2CRs by binding, inositol triphosphate (IP3) or cyclic GMP (cGMP) coupling studies in transfected fibroblasts. 3. DHE and 8'-OH-DHE are competitive compounds at 5-HT2B and 5-HT2CRs. 8'-OH-DHE interaction at (5-HT2BRs) was best fitted by a biphasic competition curve and displayed the highest affinity with a Ki of 5 nm. These two compounds acted as agonists for both receptors in respect to cGMP production with pEC50 of 8.32+/-0.09 for 8'-OH-DHE at 5-HT2B and 7.83+/-0.06 at 5-HT2CRs. 4. Knowing that the antimigraine prophylactic effect of DHE is only observed after long-term treatment, we chronically exposed the recombinant cells to DHE and 8'-OH-DHE. The number of 5-HT2BR-binding sites was always more affected than 5-HT2CRs. At 5-HT2BRs, 8'-OH-DHE was more effective than DHE, with an uncoupling that persisted for more than 40 h for IP3 or cGMP. By contrast, the 5-HT2CR coupling was reversible after either treatment. 5. Chronic exposure to 8'-OH-DHE caused a persistent agonist-mediated desensitisation of 5-HT2B, but not 5-HT2CRs. This may be of relevance to therapeutic actions of the compound.

Function of the serotonin 5-hydroxytryptamine 2B receptor in pulmonary hypertension.

Primary pulmonary hypertension is a progressive and often fatal disorder in humans that results from an increase in pulmonary blood pressure associated with abnormal vascular proliferation. Dexfenfluramine increases the risk of pulmonary hypertension in humans, and its active metabolite is a selective serotonin 5-hydroxytryptamine 2B (5-HT(2B)) receptor agonist. Thus, we investigated the contribution of the 5-HT(2B)receptor to the pathogenesis of pulmonary hypertension. Using the chronic-hypoxic-mouse model of pulmonary hypertension, we found that the hypoxia-dependent increase in pulmonary blood pressure and lung remodeling are associated with an increase in vascular proliferation, elastase activity and transforming growth factor-beta levels, and that these parameters are potentiated by dexfenfluramine treatment. In contrast, hypoxic mice with genetically or pharmacologically inactive 5-HT(2B)receptors manifested no change in any of these parameters. In both humans and mice, pulmonary hypertension is associated with a substantial increase in 5-HT(2B) receptor expression in pulmonary arteries. These data show that activation of 5-HT(2B) receptors is a limiting step in the development of pulmonary hypertension.

Developmentally regulated serotonin 5-HT2B receptors.

Serotonin (5-hydroxytryptamine, 5-HT) binds to numerous cognate receptors to initiate its biological effects. In this review, we have focused on the 5-HT2B receptor to address how signaling and expression of this receptor is specifically implicated in embryonic development and adult health and disease. Transduction of the 5-HT2B signaling is complex, including phospholipase C and A2 stimulation, cGMP production and a mitogenic signal that integrates the tyrosine kinase-signaling pathway. Furthermore, 5-HT, through the 5-HT2B receptors, has the ability to control serotonergic differentiation of committed neuron-like cells. In addition, 5-HT2B receptors are actively involved in the transient action of 5-HT during embryonic morphogenesis. Our recent data presented the first genetic evidence that 5-HT via 5-HT2B receptors regulates cardiac embryonic development and adult functions and suggested that this receptor subtype may be involved in other physiopathological situations. In particular, 5-HT-dependent molecular mechanisms may be involved in embryonic development and postnatal maturation of the enteric nervous system. Also, the involvement of the 5-HT2B receptor in the vascular growth often observed in hypertension is likely. These probably result from reactivation of developmentally regulated receptors in pathological situations. Finally, embryonic functions of 5-HT2 receptors observed in Drosophila gastrulation suggest evolutionary conserved mechanisms.

Effect of infant formula on stool characteristics of young infants.

BACKGROUND: Many infants are switched between multiple formula preparations early in life because of perceived abnormalities in stooling pattern as well as gastrointestinal symptoms. OBJECTIVE: To investigate the relationship between the type of formula consumed and the stooling characteristics and gastrointestinal symptoms of young infants. METHODS: Healthy 1-month-old infants were fed one of four commercial formula preparations (Enfamil, Enfamil with Iron, ProSobee, and Nutramigen) for 12 to 14 days in a prospective double-blinded (parent/physician) fashion. Parents completed a daily diary of stool characteristics as well as severity of spitting, gas, and crying for the last 7 days of the study period. A breast-fed infant group was studied as well. RESULTS: Two hundred eighty five infants were enrolled and 238 completed the study. Infants receiving breast milk or Nutramigen had twice as many stools as other formula groups (P < .001). Infants receiving ProSobee had hard/firm stools more often than breast-fed or other formula-fed groups (P < .00001). Watery stools were more common in infants fed Nutramigen than other formula groups (P < .04). Green stools were more common in 12 mg/L iron preparations (Enfamil with iron, ProSobee, Nutramigen) than in those with 1 mg/L (Enfamil, breast milk) (P < .00001). Spitting, gassiness, and crying were of equal severity in all formula groups. CONCLUSIONS: The interpretation of stool frequency, color, and consistency must take into account the infant's formula type as significant variations in normal infants occur. Parental education on the range of infant stooling characteristics as well as the common occurrence of spitting, gas, and crying may alleviate concern for formula intolerance and underlying gastrointestinal disease.

Percutaneous endoscopic placement of the "button" gastrostomy tube as the initial procedure in infants and children.

Percutaneous endoscopic gastrostomy (PEG) tube placement is routinely performed in children with special nutritional needs. For convenience and cosmetic reasons, many parents prefer a skin-level, nonrefluxing, ("button") gastrostomy tube. After healing of the track, a button gastrostomy tube can replace a PEG but this requires a second procedure. This study assessed the technique and complication rate of placement of a button gastrostomy tube mounted for endoscopic placement as the initial procedure. Seventeen patients (10 males), ages 4 months to 12 years were studied. All patients underwent successful placement of the button under conscious sedation using a standard endoscopic push technique. In the first 10 patients, an 18 French device was used. Four patients developed migration of the device into the track between 9 and 55 days after placement and the button was removed. Migration was preceded or accompanied by a wound infection in 3 of the 4 patients. In the next 7 patients, a larger, 24 French button was used without any wound infections or migration of the device. In thirteen patients with successful placement, a follow-up period of 110-450 days has revealed no further complications. Placement of the button gastrostomy tube in infants and children can be accomplished using standard endoscopic techniques. However, further study of the optimal size of the device and optimal placement procedure to prevent wound infection and migration should be undertaken.

Evaluation of the effect of a fiber-enriched formula on infant colic.

Because infants with colic appear to have abdominal pain similar to that of adults with irritable bowel syndrome, who may benefit from the addition of fiber to their diet, we tested whether fiber added to infant formula would alleviate colic. Twenty-seven normal, term infants (aged 2 to 8 weeks; 14 girls) with colic, defined as crying plus fussing for more than 3 hours a day for at least 3 days of a 6-day baseline period, were enrolled. Infants were randomly assigned in 9-day periods to a sequence of placebo (Isomil formula) followed by fiber-supplemented formula (Isomil plus soy polysaccharide) (n = 12) or the reverse (n = 15). Daily diaries of crying, fussing, sleeping, formula, intake, and stooling were kept. Twenty-two infants completed three lactulose breath hydrogen tests at the end of the baseline period and after each study period. The crossover trial was followed by 30 to 35 days of use of the study formula chosen by the parents as most beneficial but unknown to the investigators. Growth was monitored throughout. Serum cholesterol, calcium, phosphate, albumin, iron, and zinc concentrations were measured at the conclusion. There were no significant differences in average daily time spent by the infants in fussing and crying during ingestion of the fiber-supplemented formula. However, parents of 18 of 27 infants chose fiber-supplemented formula as most beneficial in ameliorating symptoms of colic. While the infants were consuming fiber-supplemented formula, stool frequency increased, and breath hydrogen excretion increased significantly, in response to lactulose. Growth and serum biochemical measurements were normal in all infants. Supplementation of infant formula with the level of soy polysaccharide used in this study may have reduced crying and fussing in some infants but did not affect colicky behavior in the majority of infants, who continued to cry and fuss excessively.

Pancreatitis following scoliosis surgery in children and young adults.

Forty-four patients undergoing single-stage surgery for scoliosis were monitored for biochemical and clinical evidence of pancreatitis. Six patients (14%) developed elevation of both serum amylase and lipase levels. Four of these had symptoms or signs suggestive of pancreatitis. Mean intraoperative blood loss was significantly higher in the group with pancreatitis. No significant differences were noted with regard to age, surgical technique, degree of initial or residual deformity, or length of surgery. The patients with pancreatitis required a longer average period of fasting time. Patients with prolonged ileus or abdominal pain after scoliosis surgery should be investigated for possible pancreatitis.

Olfactory identification deficits in HIV infection.

OBJECTIVE: Impaired odor identification is described in a number of CNS disorders, and human immunodeficiency virus (HIV) infects the CNS in a large percentage of patients. To evaluate whether impaired olfaction may indicate CNS disease, the authors measured odor identification in patient groups defined along a continuum of progressive immunodeficiency and in a comparison group. METHOD: Most of the 42 HIV-infected patients in the study were outpatients in a clinic specializing in treatment of HIV-infected individuals. The comparison subjects were 37 healthy age- and sex-matched individuals who were recruited from hospital and medical school personnel. Ten of the patients were HIV-seropositive but had no symptoms, 24 had clinical evidence of immunocompromise, and eight had HIV dementia. All subjects were given the University of Pennsylvania Smell Identification Test, which presents common odorants and requires the subject to identify the odor from a four-item word list. The data were analyzed by using analysis of variance after arc-sine transformation and Scheffé post hoc analysis. RESULTS: All patients scored significantly lower on the Smell Identification Test than did the comparison subjects. The patients with HIV dementia had significantly lower scores than did the other two groups of patients. CONCLUSIONS: Clinically, impaired olfaction might serve as a marker of early CNS HIV involvement. Future studies should attempt to match comparison and experimental populations for socioeconomic status and HIV risk behavior.

Pediatric liver transplantation: Part I. Choosing and caring for the transplant candidate.

Liver transplantation is now an accepted modality of treatment for acute fulminant hepatic failure, end-stage chronic liver disease and certain hepatic-based inborn errors of metabolism in children. This paper reviews the criteria used in selecting appropriate candidates for transplantation based on a knowledge of the natural history of the underlying disease and the individual patient's condition. Important clinical, laboratory, radiologic and histologic data used to make decisions regarding transplantation are reviewed. Nutritional assessment and management are emphasized as part of the comprehensive evaluation and therapeutic plan to prepare a patient for transplantation.

Pediatric liver transplantation: Part II. Managing the long-term complications.

Increasing numbers of children are receiving liver transplants at major centers and returning to their home hospitals for long-term follow-up. This review summarizes the long-term complications in pediatric liver transplant recipients and their recognition and management. Emphasis is placed on an understanding of the practical aspects of the pharmacokinetics and toxicity of cyclosporine, the major immunosuppressive drug used in these patients. Common infectious problems, particularly serious viral infections, are reviewed with their unique clinical presentations in this immunocompromised population. Therapeutic alternatives for episodes of acute rejection are offered to facilitate communication with the transplant center and familiarize the local pediatric gastroenterologist and his or her staff with the management issues facing those who take care of these complex patients.

Carbohydrate malabsorption following fruit juice ingestion in young children.

We performed breath hydrogen analyses in 13 healthy children (9 to 36 months of age) and seven children (14 to 27 months of age) with chronic nonspecific diarrhea after they had ingested pear, grape, and apple juices and a 2% sorbitol solution. Excess breath H2 excretion was found in virtually all study subjects following the ingestion of either pear juice (with approximately 2% sorbitol content) or the 2% sorbitol solution, in approximately 50% of those ingesting apple juice (0.5% sorbitol), and in 25% of those ingesting grape juice (no sorbitol) (P less than .001, analysis of variance). No differences were noted between the healthy children and those with chronic nonspecific diarrhea. Forty percent of all study subjects in whom excess breath hydrogen excretion occurred also had diarrhea and abdominal cramping. Carbohydrate malabsorption appears to be frequent following the ingestion of common fruit juices and in some children may be associated with nonspecific gastrointestinal symptoms.

[Aortic insufficiency and syphilitic coronary ostial disease. Pre- and postoperative angiographic aspects]. / Insuffisance aortique et coronarite ostiale syphilitique. Aspects angiographiques pré et postopératoires.

The authors report the case of a 50 year old patient with severe aortic incompetence (stage IV on angiography) and syphilitic left coronary ostial disease confirmed by complementary investigations. Management comprised aortic valve replacement and saphenous vein aorto-coronary bypass. The postoperative angiographic appearances showed normal valve function and a permeable aorto-left anterior descending bypass graft. The outcome was also satisfactory from the clinical point of view.