Can C-reactive protein, procalcitonin and mid-regional pro-atrial natriuretic peptide measurements guide choice of in-patient or out-patient care in acute pyelonephritis? Biomarkers In Sepsis (BIS) multicentre study.

Whereas C-reactive protein (CRP), procalcitonin (PCT) and mid-regional pro-atrial natriuretic peptide (ANP) may be of use at the bedside in the management of adult patients with infectious disorders, their usefulness has not been established in the setting of acute pyelonephritis. To assess the effectiveness of CRP, PCT and ANP measurements in guiding emergency physicians' decisions whether to admit to hospital patients with acute pyelonephritis, we conducted a multicentre, prospective, observational study in 12 emergency departments in France; 582 consecutive patients were included. The reference standard for admission was defined by experts' advice combined with necessity of admission or death during the 28-day follow-up. Baseline CRP, PCT and ANP were measured and their accuracy in identifying the necessity of admission was analysed using area under curves (AUC) of receiver-operating characteristic (ROC) plots. According to the reference standard, 126 (22%) patients required admission. ANP (AUC 0.75, 95% CI 0.69-0.80) and PCT (AUC 0.75, 95% CI 0.71-0.80) more accurately predicted this than did CRP (AUC 0.69, 95% CI 0.64-0.74). The positive and negative likelihood ratios for each biomarker remained clinically irrelevant whatever the threshold. Our results did not support the use of these markers to help physicians in deciding about admission of patients experiencing acute pyelonephritis in daily practice.

[A case of association of atypical localisations of Streptococcus pneumoniae]. / Association de localisations atypiques à Streptococcus pneumoniae: à propos d'un cas.

Streptococcus pneumoniae can be responsible for spinal, joints, pulmonary or infrequently cutaneous septic localisations. The association between different septic localisation is extremely rare with this microorganism. We describe the first case of concomitant spinal, joints and cutaneous septic localisations in a critically ill patient with S. pneumoniae septicaemia. This observation illustrates that heterogeneity of clinical features depends on the pathogen characteristic and its interaction with the host.

The cumulative occurrence of resistance mutations in the HIV-1 protease gene is associated with failure of salvage therapy with ritonavir and saquinavir in protease inhibitor-experienced patients.

Salvage therapy with ritonavir (RTV) and saquinavir (SQV) failed to achieve virological and immunological improvement in 24 HIV-infected patients who discontinued triple therapy with RTV or indinavir (IDV) because of failure or intolerance to treatment. Changes in the HIV-1 protease gene sequence were analyzed prospectively in 14 patients. No primary protease mutation was found prior to the use of protease inhibitors. After 7 months of treatment with IDV or RTV, primary resistance mutations at codons pol 46 and/or pol 82 were observed in 11 of 13 patients. After 16 weeks on RTV-SQV, novel primary mutations related to SQV emerged in 7 of 13 patients, together with an increase in the number of secondary resistance mutations. Our observations indicate that the cumulative occurrence of resistance mutations in the protease gene was associated with failure of antiretroviral therapy. The presence of mutations to a first protease inhibitor may represent a risk factor for the failure of a subsequent treatment with a second line protease inhibitor.

[Adherence to antiretroviral treatments with a protease inhibitor in HIV-infected patients]. / Enquête sur l'observance des traitements antirétroviraux comportant un inhibiteur de protéase chez les patients infectés par le VIH.

OBJECTIVE: Long-term therapeutic success of powerful antiretroviral treatments dependent on patient adherence. This study was conducted to assess the difficulties HIV-infected patients with advanced-stage disease encounter in adhering to antiretroviral treatments with a protease inhibitor. PATIENTS AND METHODS: A prospective self-administered questionnaire survey was conducted at our outpatient clinic for 2 months. CD4 counts and HIV viral loads were also determined. RESULTS: Seventy-one percent of the study population which included 262 responded to the questionnaire. The survey was made a median 215 days after initiating the antiprotease treatment with indinavir (71% of the cases), ritonavir (13%), saquinavir (6%), or a combination of protease inhibitors (10%). At onset of antiprotease treatment, mean CD4 count was 171+/-150/mm(3) and mean HIV viral load was 75,000 copies/ml. The treatment was considered to be difficult to take by 43% of the patients; 66% stated they had forgotten to take their drugs at least once a month. It was most difficult to take the drugs prescribed for the afternoon. Shifts of 1 hour were observed in 58% of patients. Non-adherence was frequent (1 failure to take drugs per week), observed in 13% of patients. Most often, the patients stated they had forgotten to take their drugs because of occupational or relational difficulties (52%). Non-adherence increased with duration of treatment. The drug most often associated with non-adherence was indinavir (73%). Age and sex did not influence adherence. Mean RNA HIV serum level was lower than at onset of the antiprotease treatment in the most non-adherent patients. At the time of the questionnaire, there was no difference in serum RNA HIV level or in the percentage of patients with an undetectable level between non-adherent and adherent patients. CONCLUSION: This survey confirmed difficulties in adherence are frequent and worsen with time. No relationship was found between non-adherence and reduction in viral load, suggesting that a short-term effect of these very active drugs despite lack of perfect adherence. Other factors (pharmacology, sensitivity to antiretroviral drugs.) also play a major role in therapeutic success.

The contribution of uniparental disomy to congenital development defects in children born to mothers at advanced childbearing age.

Most instances of maternal uniparental disomy (UPD) start as trisomies and, similar to the latter, show a significant increase of mean maternal age at delivery. To investigate the incidence of UPD in offspring of older mothers, we investigated two groups of patients: 1) 50 patients with unclassified developmental defects born to mothers 35 years or older at delivery were tested for UPD for all autosomes by means of microsatellite marker analysis; 2) The incidence of UPD versus other etiologies in correlation, with maternal age below versus 35 years and above at delivery was studied in patients investigated in our laboratory for maternal UPD 15 (Prader-Willi syndrome, PWS), paternal UPD 15 (Angelman syndrome, AS), and maternal UPD 7 (Silver-Russell syndrome, SRS). In group 1, four patients of 50 showed UPD for an autosome that clarified the etiology of their developmental problems: a 27-year-old woman with growth retardation and early puberty disclosed maternal heterodisomy 14; a 15-year-old girl revealed paternal isodisomy 15; a 6-year-old boy with suspected Smith-Lemli-Opitz syndrome was shown to have maternal heterodisomy 16 with additional mosaic partial trisomy 16(pter-p13); a 16-month-old girl with intrauterine growth retardation and a dysmorphic pattern revealed maternal heterodisomy 7. In group 2 the offspring of older mothers showed a clear increase of UPD compared with the mothers below 35 years at delivery. The binomial distribution gave P-values of 1.9 x 10(-10), 2.6 x 10(-4), and 0.01 for PWS, AS, and SRS, respectively. The correlation between increase of paternal UPD 15 with advanced maternal age might be explained by maternal non-disjunction leading to hypohaploid gamete (nullisomy) for chromosome 15 with subsequent or concomitant duplication of the paternal homologue (paternal isodisomy). The three UPD 15 AS cases with mothers older than 35 years at delivery revealed isodisomy, whereas the three cases from younger mothers showed heterodisomy. This study confirms the hypothesis that uniparental disomy is a not negligible cause of congenital developmental anomalies in children of older mothers.

Maternal uniparental disomy 14 as a cause of intrauterine growth retardation and early onset of puberty.

Uniparental disomy for particular chromosomes is increasingly recognized as a cause of abnormal phenotypes in humans either as a result of imprinted genes or, in the case of isodisomy, homozygosity of mutated recessive alleles. We report on the occurrence of maternal uniparental disomy for chromosome 14 (matUPD 14) in a 25-year-old woman with a normal karyotype, normal intelligence but low birth weight, short stature, small hands, and early onset of puberty. Comparison of her phenotype with those of 15 previously described liveborn patients with matUPD14 gives further evidence for an imprinted gene region on chromosome 14 and highlights the necessity to consider this cause in children with intrauterine growth retardation and early onset of puberty caused by acceleration of skeletal maturation.

Ergotism related to a single dose of ergotamine tartrate in an AIDS patient treated with ritonavir.

We report a rare case of ergotism related to a single dose of ergotamine tartrate in a man with AIDS being treated with ritonavir. He was treated with a prostacyclin analogue and made a complete recovery.

Neurite fasciculation mediated by complexes of axonin-1 and Ng cell adhesion molecule.

Neural cell adhesion molecules composed of immunoglobulin and fibronectin type III-like domains have been implicated in cell adhesion, neurite outgrowth, and fasciculation. Axonin-1 and Ng cell adhesion molecule (NgCAM), two molecules with predominantly axonal expression exhibit homophilic interactions across the extracellular space (axonin- 1/axonin-1 and NgCAM/NgCAM) and a heterophilic interaction (axonin-1-NgCAM) that occurs exclusively in the plane of the same membrane (cis-interaction). Using domain deletion mutants we localized the NgCAM homophilic binding in the Ig domains 1-4 whereas heterophilic binding to axonin-1 was localized in the Ig domains 2-4 and the third FnIII domain. The NgCAM-NgCAM interaction could be established simultaneously with the axonin-1-NgCAM interaction. In contrast, the axonin-1-NgCAM interaction excluded axonin-1/axonin-1 binding. These results and the examination of the coclustering of axonin-1 and NgCAM at cell contacts, suggest that intercellular contact is mediated by a symmetric axonin-12/NgCAM2 tetramer, in which homophilic NgCAM binding across the extracellular space occurs simultaneously with a cis-heterophilic interaction of axonin-1 and NgCAM. The enhanced neurite fasciculation after overexpression of NgCAM by adenoviral vectors indicates that NgCAM is the limiting component for the formation of the axonin-12/NgCAM2 complexes and, thus, neurite fasciculation in DRG neurons.

[Sarcoidosis and pregnancy. A retrospective study of 11 cases]. / Sarcoïdose et grossess. Etude retrospective de 11 cas.

PURPOSE: To analyze the evolutive profile of sarcoidosis together with reciprocal interactions between pregnancy and sarcoidosis. METHODS: All events that occurred during pregnancy in 11 women presenting with sarcoidosis were analyzed. Histological confirmation was obtained for the 11 cases. For all pregnancies were analyzed the course of both sarcoidosis and pregnancy, and the influence of pregnancy on the disease evolution. RESULTS: Among 33 pregnancies, 23 led to the birth of healthy fetuses (five spontaneous abortions, four voluntary abortions, and one therapeutic abortion). The major event was fetal hypotrophy in six cases. Three of them occurred during pregnancy in prednisone-treated patients with active sarcoidosis. No relapse of cured sarcoidosis or further evolution of sarcoidosis that was inactivated as of the beginning of pregnancy were observed. The course of active sarcoidosis varied, as improvement (one case), worsening (two cases) and stabilization (two cases) were observed. During the first year of follow-up after delivery, four relapses and, in two cases, preliminary signs of the disease were observed. CONCLUSION: Apart from the hypothetical but not definite risk of hypotrophy, no negative interaction between sarcoidosis and pregnancy could be established. Pregnancy does not seem to interfere with the course of sarcoidosis. Considering the risk of relapse after delivery, pregnant women presenting with sarcoidosis should benefit from clinical and radiological follow-up.

[Acyclovir-resistance zona in a immunocompromised HIV seronegative patient]. / Zona résistant à l'aciclovir chez un malade immunodéprimé non infecté par le VIH.

INTRODUCTION: Resistance to antiviral therapy is getting actually more frequent. Immunocompromised host are more concerned with this problem. OBSERVATION: We present a case of disseminated zoster resisting to acyclovir (ACV) therapy, but healing with foscarnet in a man treated with chemotherapy for lymphoma and seronegative for HIV. CI50 of VZV strain was 48 microM for ACV, which was 2.8 times higher than value of the reference OKA strain tested simultaneously, which confirmed the resistance for ACV. DISCUSSION: Immunocompromised patients often present varicella zoster virus (VZV) infection. They usually heal in response to ACV therapy, but some HIV infected patients have already presented with resistant strains of VZV. This case is the first described in a non-HIV infected patient. Foscarnet therapy resulted twice in complete healing because of its direct activity on viral DNA polymerase, so it is efficaceous therapy for patients with thymidine-kinase-deficient ACV-resistant VZV infection.

Fever after craniofacial surgery in the infant under 24 months of age.

A retrospective review was undertaken of 126 consecutive craniofacial procedures involving a transcranial component, performed at the Children's Medical Center at Dallas, between 1990 and 1994. Standard postoperative axillary temperature measurements were recorded until discharge. Age at surgery of less than 24 months correlated very strongly with a postoperative temperature of greater than 38 degrees C (r = -0.92). The incidence of postoperative fever was high in all age groups, yet there was still a significant difference between the group younger than 2 years and the group in which surgery was performed after the age of 2 years across all postoperative temperature ranges, from >38 degrees C to >39.5 degrees C (p < 0.001, chi-square test). The white blood cell count was elevated above the age-related normal in 67 percent of febrile patients. There was no correlation between type or duration of surgical procedure, length of intensive care or hospital stay, or the need for blood transfusion and the development of a significant postoperative fever. There were minor infectious complications in four patients (3 percent), only one of which was a wound problem related to the surgery. All infectious complications were easily identifiable clinically. There was no mortality or serious infections. The development of postoperative fever, and an elevated white blood cell count, is to be expected in pediatric patients undergoing craniofacial procedures. The routine laboratory investigation of postoperative fever in pediatric craniofacial patients under 2 years of age without procedures involving transgression of the paranasal sinuses is not warranted unless there are associated clinical indicators.

Nasal septal hematoma.

Nasal septal hematoma is a rare but potentially serious complication of nasal trauma. Proper management consists of early recognition, prompt surgical evacuation of the hematoma, and antimicrobial therapy if a secondary nasal septal abscess is suspected. Clindamycin is recommended as initial therapy until the results of cultures and susceptibility studies are available.

HIV combination therapy: immune restitution causing cryptococcal lymphadenitis dramatically improved by anti-inflammatory therapy.

Two patients with AIDS developed microscopically verified focal cryptococcal lymphadenitis while treated with highly active anti-retroviral therapy for 8 and 15 months. Both were treated with fluconazole as a secondary prophylaxis for prior cryptococcal meningitis. Cryptococcus neoformans did not grow. Amphotericin was ineffective. Anti-inflammatory drugs had a dramatic effect.

Frontal sinus fractures.

Frontal sinus fractures are rare in children, uncommon in adolescents, and most commonly the result of high-impact collisions of the face with an immovable object. Most are associated with other facial and head injuries; intracranial injury should be considered an invariable concomitant of any frontal sinus fracture that involves the posterior sinus wall. Proper management of frontal sinus fractures requires a multidisciplinary team approach.

Upper airway obstruction caused by brown recluse spider envenomization of the neck.

A 7-year-old boy presented to the emergency department with progressive cervical soft tissue swelling and airway compromise due to envenomization by a brown recluse spider. This life-threatening complication is an extremely unusual presentation of brown recluse spider envenomization. Previous published reports have centered on the disfiguring localized tissue necrosis or life-threatening systemic reactions that occur secondary to the spider's venom.