[Clinical research in pediatric practice applied to ambulatory infectious pathology].
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Anti-Bacterial Agents↗
Biomedical subjects
C Levy
Publications and source records attributed to C Levy.
Brain stem MRI signal abnormalities in CADASIL.
BACKGROUND: We recently showed that the severity of MRI signal abnormalities increases with age in CADASIL, an arteriopathy due to mutations of notch 3 gene on chromosome 19. Previous results also suggest that the various hemispheric subcortical areas have a different vulnerability to ischemia in this disease. The distribution of the lesions at the brain stem level has not yet been reported. CASE DESCRIPTIONS: We reviewed the MRIs of 68 affected patients having signal abnormalities in the hemispheric white matter to assess the distribution and clinical consequences of brain stem signal abnormalities in CADASIL. We found hypersignals on T2-weighted images in the brain stem in 45% of the subjects. The pons was more frequently involved (100%) than the mesencephalon (69%) and the medulla (35%). Hyposignals on T1-weighted images, at the brain stem level, were observed only in two thirds of these subjects. The lack of signal abnormalities reaching the brain stem surface and the absence of cerebellar lesions were noteworthy. CONCLUSIONS: Brain stem signal abnormalities observed in CADASIL are found in regions irrigated only by perforating arteries. These results support parallel observations made for CADASIL-associated signal abnormalities in the cerebral hemispheres and emphasize the importance of the angioarchitecture of the cerebral vasculature to explain why a condition characterized by a systemic vessel wall pathology is manifested only as a brain disease.
Brain Stem↗
[Prognostic factors in malignant melanoma of the conjunctiva. An anatomo-clinical study of 56 patients].
UNLABELLED: We have reviewed a serie of 56 patients treated in our Institute for malignant melanoma of the conjunctiva between 1980 and 1992. We selected cases where histology had been reviewed. PATIENTS AND METHOD: The median follow up is 96 months. The age varies from 13 to 88 years with a mean age of 56 years. There were 22 men and 34 females. In 29 cases (51%) the melanoma appeared de novo, ten cases (17%) it derived from a naevus and in 14 cases (25%) on a precancerous melanosis. The tumour was localized at the limbus and bulbar conjunctiva in 57% of cases. The mean diameter was 6.1 mm and the mean thickness was 2.3 mm. The treatment consisted in surgical excision of the tumour followed by external beam radiothérapy in 49 cases. Histological examination showed invasion of the chorion in 44 cases (78%) and of the sclera in 6 cases (1%). RESULTS: 38 patients are alive and 29 without disease. 2 with disease, 7 lost follow-up. 18 patients died (32%) and among them 14 (25%) died of metastatic disease. 22 patients (39%) have presented local recurrence and among them 10 have had multiple recurrences. The mean delay for recurrence was 56 months. The overall survival was 77% at 5 years and 64% at 10 years. Tumours appeared de novo have a worse prognosis. If we consider the localization tumour located at the limbus or on bulbar conjunctiva have less metastasis. CONCLUSION: Malignant melanoma of conjunctiva is a tumour that can frequently recur. Metastasis are not infrequent and follow up must be prolonged.
Adolescent↗
Hereditary cerebral cavernous angiomas: clinical and genetic features in 57 French families. Société Française de Neurochirurgie.
BACKGROUND: Cavernous angiomas, which are vascular malformations mostly located in the central nervous system, may be inherited as an autosomal dominant disorder known as familial cerebral cavernoma (FCC). FCC has been studied in Hispanoamerican families, in which a strong founder effect was shown. We studied the families of 57 non-Hispanic patients with cavernous angiomas. METHODS: All 28 neurosurgery centres in France collaborated in the study. Inclusion criteria were: families of index patients known to have at least one clinically affected relative, and families of index patients with multiple cavernous angiomas who initially presented as sporadic cases. Clinical and cerebral magnetic resonance imaging (MRI) investigations were done in all patients and in other at-risk individuals who consented to take part. FINDINGS: On MRI, 16 of 22 sporadic index patients had relatives with cavernous angiomas. 51 multiple-case families, including 100 patients with symptoms and 164 symptom-free individuals had MRI lesions. Most FCC patients had multiple lesions and there was a strong correlation between number of lesions and age (p<0.01). The sensitivity of gradient-echo sequences was higher than that of standard MRI for detection of small cavernous angiomas. Pattern of inheritance was autosomal dominant, with incomplete clinical penetrance. The occurrence of de-novo mutations was strongly suggested in some families. INTERPRETATION: Neuroimaging penetrance of FCC is much higher than clinical penetrance. 75% of sporadic cases with multiple lesions are in fact familial cases. The proportion of patients developing clinical symptoms is higher in the hereditary form than in the sporadic form of the disorder.
Adolescent↗
A multicenter, randomized, double-blind trial of 5 versus 10 days of antibiotic therapy for acute otitis media in young children.
BACKGROUND: All but 2 of the 15 published trials have failed to show a difference in efficacy between short (3 to 5 days) and standard (7 to 10 days) antibiotic regimens for acute otitis media (AOM). These studies involved relatively few patients under 2 years of age, who are at a higher risk for treatment failure. METHODS: In a prospective, comparative, double-blind, randomized, multicenter trial, we compared amoxicillin/clavulanate in 3 divided doses for 10 days with an identical 5-day regimen, followed by a 5-day placebo period. RESULTS: Between February 1995 and May 1996, 385 children (mean age, 13.3 months) were enrolled, 194 in the 5-day treatment group and 191 in the 10-day treatment group. In the per protocol analysis, clinical success was obtained on days 12 to 14 after the beginning of treatment (main analysis) in 125 (76.7%) of the 163 children receiving the 5-day regimen and 148 (88.1%) of the 168 receiving the 10-day regimen (P = .006). Clinical success persisted on days 28 to 42 among 57 (40.4%) of the 141 assessable patients in the 5-day group and 64 (46%) of the 139 assessable patients in the 10-day group. (P = .34). Multivariate analysis showed that the 10-day course was statistically superior only among children cared for outside their homes (86.8% vs 70.8%; P = .008). CONCLUSIONS: When assessed on days 12 to 14 after the outset of treatment, a 5-day regimen is not equivalent to a 10-day regimen among young children with AOM.
Acute Disease↗
Treatment of liver metastases from uveal melanoma by combined surgery-chemotherapy.
AIMS: To investigate sporadic results demonstrating prolonged survival after surgical resection and/or intraarterial chemotherapy (IACH) for liver metastases from uveal melanoma. METHODS: From December 1992 to March 1997 every patient with liver metastases from uveal melanoma was enrolled in a prospective study including: (1) aggressive surgical approach removing as much liver disease as possible; (2) implantation of an intraaterial catheter; (3) intraarterial chemotherapy for 6 months. 75 patients were enrolled: 38 men, 37 women, mean age 51 years (range: 18-72), mean time from initial diagnosis of uveal melanoma to liver metastases 37 months (ranged: 1-168). RESULTS: Disseminated disease in both lobes was present in all but one patient. Macroscopically curative surgery was possible in 27.5%. Significant tumour reduction was performed in 49.3% and a simple biopsy was possible in 23.2%. Eight patients did not receive chemotherapy and died soon after. IACH included Fotemustine and/or DTIC-Platinum for 4-9 cycles. Overall median survival was 9 months; very similar to non-operated historical controls. In the 61 patients receiving complete treatment surgery plus chemotherapy, median survival improved to 10 months. When curative resection was possible, survival increased to 22 months (P < 0.001). CONCLUSIONS: Aggressive surgical resection, when possible, appears to be the best method of improving survival of liver metastases from uveal melanoma. New drug combinations are also required to improve survival.
Adult↗
Role of chemotherapy alone or in combination with hyperthermia in the primary treatment of intraocular retinoblastoma: preliminary results.
BACKGROUND: The efficacy of the etoposide-carboplatin combination in extraocular retinoblastoma is well known. This drug combination is therefore used in intraocular retinoblastoma, as primary reduction chemotherapy, before local treatment. The use of carboplatin in combination with diode laser hyperthermia as local treatment (thermochemotherapy) has been recently described as a conservative approach avoiding external beam radiotherapy in posterior pole tumours. METHODS: All patients were reviewed, who were treated for retinoblastoma at the Institut Curie between June 1994 and October 1995, in whom treatment included either reduction chemotherapy or thermochemotherapy or both modalities successively. 23 patients presenting with unilateral (three) or bilateral (20) intraocular retinoblastoma received neoadjuvant chemotherapy consisting of two courses of etoposide 150 mg/m2/day and carboplatin 200 mg/m2/day for 3 days. 15 patients (17 eyes), eight of whom had already received neoadjuvant chemotherapy, were treated by thermochemotherapy. RESULTS: Neoadjuvant chemotherapy: overall, seven eyes in seven patients could be treated conservatively, avoiding external beam irradiation, with a median follow up of 14 months. Thermochemotherapy: external beam irradiation was avoided for 14 of the 17 eyes treated. CONCLUSION: Integration of neoadjuvant chemotherapy and combined treatment with carboplatin and diode laser, into the therapeutic armamentarium for retinoblastoma allows use of more aggressive treatments such as enucleation and external beam radiation.
Antineoplastic Combined Chemotherapy Protocols↗
Patterns of MRI lesions in CADASIL.
OBJECTIVE: To investigate the location and severity of MRI signal abnormalities in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). BACKGROUND: One hallmark of this arteriopathy due to mutations of Notch 3 gene is the presence of MRI signal abnormalities in both symptomatic and asymptomatic patients. METHODS: MRIs of 75 patients (43 with symptoms) were reviewed by a neuroradiologist masked to their clinical status. After assessing the presence of MRI lesions on T1- and T2-weighted images (T1-WI, T2-WI) in different subcortical regions, the severity of hyperintensities on T2-WI was scored using a global rating scale and a regional semiquantitative scale in the periventricular white matter (PV), deep white matter (WM), basal ganglia (BG), and infratentorial areas (IT). RESULTS: Sixty-eight patients (90%) had hyperintensities on T2-WI located in the white matter, more frequent in PV (96%) and WM (85%) than in the superficial white matter (25%). Hyperintensities also occurred in BG (60%) and brainstem (45%). Forty-seven patients (62%) presented with hypointensities on T1-WI. In one-third of the affected individuals, white matter hyperintensities occurred in the absence of small deep infarcts on T1-WI. The frequency and severity scores calculated for PV, WM, BG, or IT hyperintensities increase dramatically with age. These scores were higher in symptomatic compared with asymptomatic gene carriers. Dementia, Rankin score > 1, or both occurred only in the presence of diffuse white matter signal abnormalities. CONCLUSION: Our results suggest that different subcortical areas have different vulnerabilities to ischemia in CADASIL. The age effect we observed may show an accumulation of lesions with aging during the course of the disease. A prospective study is needed to investigate if the rating of MRI lesions is of prognostic value in CADASIL.
Adult↗
[Magnetic resonance angiography of the carotid artery: artifacts, anatomy, diseases].
Magnetic resonance angiography is now a technique commonly used in neurologic practice. We give a brief overview of the biophysical principles of this technique. Recent refinements and technical innovations are also noted. After some anatomic considerations about the carotid artery, we provide some data about the role of MRA in atherosclerotic and non atherosclerotic diseases (dissections, aneurysms, arteritis, post operative follow-up...) of the extra and intracranial carotid arteries. The purpose of this review is to concentrate on the role of magnetic resonance angiography in patients with various carotid artery diseases and to specify possibilities, limitations and risk of misinterpretation. Magnetic resonance angiography is a major, still evolving technique.
Adult↗
[Unilateral retinoblastomas with late bilateralization. Three case reports].
Three cases of unilateral retinoblastoma with late bilateralization are presented in this study. The rare occurrence of this event underlines the need for prolonged follow-up in the fellow-eye, even in the absence of familial retinoblastoma. In these three cases, the first affected eye was enucleated after a diagnosis made at three months, sixteen months and three years of age. New tumors appeared in the second eye when the children were sixteen years old in one case and five years old in two cases.
Adolescent↗
[Initial results of proton therapy in choroidal melanoma at the d'Orsey Center for Proton Therapy; the first 464 cases].
PURPOSE: Retrospective analysis of the treatment of choroidal melanoma with protontherapy at the Centre de protonthérapie d'Orsay, France. PATIENTS AND METHODS: Between September 1991 and September 1995, 612 patients presenting with choroidal melanoma were treated by protontherapy in Orsay. Following initial management of the first 464 patients, results were analyzed, as were results after a 1-year follow-up for 305 patients, a 2-year follow-up for 169 patients, and a 3-year follow-up for 59 patients. RESULTS: Univariate analysis showed that the actuarial local recurrence rate was 5%, the 3-year survival rate 88%, and the overall metastasic rate 5%. The initial tumor volume was the most significant predictive factor for visual results and metastases. Multivariate analysis revealed that visual results were significantly related to the initial tumor volume, initial retinal detachment, and total dose delivered to the optic nerve and macula. CONCLUSION: Protontherapy of choroidal melanoma allows in most cases conservation of the eye without modification of survival. Visual results mainly depend on the site and size of the tumor.
Choroid Neoplasms↗
Change in nasopharyngeal carriage of Streptococcus pneumoniae resulting from antibiotic therapy for acute otitis media in children.
BACKGROUND: Acute otitis media is the leading reason for antibiotic prescriptions in childhood. The increase in antibiotic resistance of Streptococcus pneumoniae is generally attributed to the extensive use of antibiotics and the selective pressure on the bacterial strains of the nasopharyngeal flora. OBJECTIVE: To evaluate the change in nasopharyngeal carriage of S. pneumoniae during antibiotic therapy prescribed for acute otitis media. METHODS: Between October, 1993, and March, 1994, we conducted a clinical trial comparing cefpodoxime-proxetil and amoxicillin-clavulanate in acute otitis media. From 364 children, 4 months to 4.5 years old, a nasopharyngeal sample was obtained before and after treatment. Antibiotic susceptibility was established by determining minimal inhibitory concentrations by the agar dilution method. Serotype and randomly amplified polymorphic DNA analysis were used to compare pre- and posttreatment S. pneumoniae strains. RESULTS: The risk for a child to carry penicillin-resistant S. pneumoniae (MIC > or = 0.125 mg/l) did not increase after antibiotic treatment: 84 of 364 (23.1%) before, 70 of 364 (19.2%) after. There was a significant decrease of penicillin-susceptible S. pneumoniae carriage, 117 of 364 (32.1%) before treatment compared with 24 of 364 (6.6%) (P = 0.0001) after treatment. However, among the children carrying S. pneumoniae at the end of the treatment there was an increase in the percentage of penicillin-resistant pneumococci: 84 of 201 (41.8%) before treatment and 70 of 94 (74.5%) after treatment. Among the 94 children carrying S. pneumoniae at the end of the treatment, 22 did not harbor pneumococcus before, 16 carried another genotypically different serotype and 56 harbored the same serotype. Among these 56 children 2 patients harbored strains that had increased MICs for the tested beta-lactam antibiotics. The randomly amplified polymorphic DNA analysis showed that in one case, the strains were genetically different. CONCLUSIONS: These data illustrate that antibiotic therapy did not increase the rate at which children carried penicillin-resistant S. pneumoniae, but there was an increase in the rate of resistance among the children carrying pneumococci at the end of the treatment, mainly as a result of reduction of susceptible strains.
Acute Disease↗
Six-day amoxicillin vs. ten-day penicillin V therapy for group A streptococcal tonsillopharyngitis.
OBJECTIVE: To compare the efficacy and safety of amoxicillin (50 mg/kg/day divided twice daily) for 6 days and penicillin V (45 mg/kg/day divided into three doses/day) for 10 days in children with group A streptococcal (GAS) tonsillopharyngitis. METHODS: In a prospective, comparative, open, randomized, multicenter trial, children were scheduled to return for visits 4 days (main end point) and 1 month after the completion of treatment for clinical and bacteriologic assessment. Total DNA restriction fragment length polymorphism was used to compare pre- and posttreatment GAS isolates. RESULTS: Between September, 1993, and February, 1995, 321 children (161 amoxicillin, 160 penicillin V) were enrolled, among whom 318 (160 amoxicillin, 158 penicillin V) were evaluable for safety, and 277 were evaluable for efficacy. Four days after the completion of treatment, pretreatment GAS were eradicated from 118 of the 141 children receiving amoxicillin (83.7%) and 116 of the 136 (85.3%) taking penicillin. One month after the outset of treatment, bacteriologic relapses were observed in 9.9% (n = 11) of the children receiving amoxicillin and 5.7% (n = 6) of those treated with penicillin V, bacteriologic recurrences in 5 and 3 patients, respectively. Adverse events related to the study medications were reported in 4 patients in the amoxicillin group and 8 in the penicillin V group. Drug-related adverse events leading to treatment discontinuation occurred in 3 patients, all in the penicillin V group. Compliance, based on diary cards and the weight of study drugs returned, was significantly better in the amoxicillin group. CONCLUSIONS. The efficacy and safety of amoxicillin (50 mg/kg/day twice daily) for 6 days were not statistically different from those of penicillin (45 mg/kg/d three times a day) for 10 days in the treatment of GAS tonsillopharyngitis.
Adolescent↗
Developing health administration education leaders: the ACEHSA Fellowship experience.
The ACEHSA Fellowship was initially established as a professional and leadership development activity for individuals from academic and professional backgrounds. The Fellow plays an integral and critical role in the accreditation process. This key role of the Fellow is presented from former and current perspectives. Also, this discussion revisits the analysis of the Fellowship experience from the original study conducted by Fine (1984) and draws comparisons with data from a current study. The results demonstrate similarities in the role over time. The Fellowship experience appears to have a direct and positive impact on the ability of individuals to personally network with other professionals, which facilitates the opportunity to acquire future leadership roles. The authors of this study served as Fellows from 1993-1994. During that time, Dr. Sobczak was honored as Senior Fellow for his contributions to the Commission.
Accreditation↗
A managed care workstation for support of ambulatory care in Veterans Health Administration medical centers.
This paper describes the development of a Managed Care Workstation for implementation in a Department of Veterans Affairs hospital. Each VA hospital information system contains a wealth of information in a comprehensive and well integrated M database, however, a clinician's access to the information is hampered by a lack of usable database tools. The Managed Care Workstation is designed to enhance access to VA databases. The workstation uses M (Mumps) and SQL to present the VA's M hierarchical database as relational tables on the workstation. This work reveals the benefits of using a SQL-M workstation to access data contained in an M based hospital information system and demonstrates how the workstation architecture supports the information model necessary for management of patient care outcomes.
Ambulatory Care Information Systems↗
Synergistic reversal of multidrug-resistance phenotype in acute myeloid leukemia cells by cyclosporin A and cremophor EL.
Cremophor (Crem) EL, the vehicle for intravenous delivery of cyclosporin A (CsA), has been reported to counteract multidrug resistance (MDR) in P-glycoprotein (Pgp)-over-expressing cell lines. Because of this, we sought to determine whether Crem functions independently as a modulator of MDR in blast cells obtained from acute myelogenous leukemia (AML) patients, and the nature of its interaction in combination with CsA in reversing an MDR phenotype. In the phenotypically classical MDR AML cell lines HL-60/Vinc (overexpresses Pgp) or HL-60/AR (does not overexpress Pgp), the dose causing half-maximum enhancement (D50) of daunorubicin (DNR, 1 micrograms/mL, 3 hours) accumulation was achieved by the combination of CsA and Crem (CsA/Crem) at 1.2 mumol/L CsA. In contrast, the D50 for Crem alone was approached at an amount that would be needed to suspend 6.2 mumol/L CsA for HL-60/Vinc, and 81 mumol/L CsA for HL-60/AR. The D50 concentrations for CsA alone (dissolved in ethanol, which does not alter DNR accumulation) were also higher than those for CsA/Crem, being 6.5 mumol/L for HL-60/Vinc, and 3.1 mumol/L for HL-60/AR. The maximum absolute level of enhancement of DNR accumulation (Emax) in each cell line was approximately equivalent for CsA/Crem or CsA alone, and was equal to the 3 hr intracellular DNR accumulation observed in parental, drug sensitive HL-60/W cells. For Crem alone, HL-60/AR and HL-60/Vinc cells showed markedly different responses: HL-60/Vinc cells attained intracellular DNR content comparable to HL-60/W, whereas HL-60/AR cells achieved only approximately 35% of this level. Multiple-drug effects were analyzed by calculation of the Combination Index (Chou and Talalay, Adv Enzyme Regul 22:27, 1984), which indicated that CsA and Crem are synergistic in causing enhancement of DNR accumulation in these MDR HL-60 cell lines. In blasts from AML patients, 5 mumol/L CsA/Crem or an equivalent amount of Crem alone each caused significant (P < .001) enhancement of DNR accumulation (60 AML-patient marrow samples) or DNR retention (51 AML-patient marrows). Similarly, CsA/Crem or Crem alone caused significant (P < .01) enhancement of the cytotoxicity of DNR in 36 AML blast cell specimens. The degree of enhancement of accumulation/retention or cytotoxicity by CsA/Crem was approximately equivalent to that obtained with Crem alone. These studies indicate that Crem can reverse an MDR phenotype in patient AML blast cells.(ABSTRACT TRUNCATED AT 400 WORDS)
Cell Survival↗
Delayed diagnosis of pulmonary tuberculosis in city hospitals.
BACKGROUND: Delays in the diagnosis of tuberculosis may result in increased patient morbidity and in further spread of the disease. We examined the clinical acumen of the medical staff in the diagnosis of tuberculosis and investigated the reasons for delay in the identification and treatment of patients with pulmonary tuberculosis. METHODS: A retrospective chart review was undertaken between July 1985 and June 1988 on all patients with culture-proven pulmonary tuberculosis at two inner city hospitals. Time intervals between admission and the clinical suspicion, diagnosis, and treatment of tuberculosis were determined. Clinical features were evaluated for their effect on these time intervals. RESULTS: Eighty-five patients with culture-proven pulmonary tuberculosis were identified. Tuberculosis was suspected in 36 patients on admission. By the end of 1 week, tuberculosis was confirmed in 50 patients and suspected in 23 others. Twenty percent of patients either died or were discharged before the diagnosis of tuberculosis was made. Older patients (> 65 years) were misdiagnosed more commonly than younger patients (82% vs 48%). Patients without respiratory symptoms were misdiagnosed more frequently (78% vs 49%) than were those with symptoms. Other reasons for delayed diagnosis and treatment included low use of tuberculin skin tests, misinterpretation of unusual chest roentgenograms, and waiting for culture results in patients with negative acid-fast smears. CONCLUSIONS: The diagnosis and treatment of patients with pulmonary tuberculosis is often delayed owing to atypical presentations and slow confirmation by culture. Improved clinical acumen, development of rapid diagnostic tests, and the institution of early empiric therapy are desirable to control this disease.
Adult↗
Experimental perturbation of the development of sexual size dimorphism in the mouse skeleton.
BALB/c mice were raised for 30 days under nine treatment regimens to determine their effects on sexual dimorphism for size of the femur and of the body. Treatment groups were divided into three experiments: 1) burrowing in a high litter cage; eight times normal gravity for a total of one hour per day; a voluntary exercise control. 2) Unilateral femoral and sciatic nerve ablation; the opposite unoperated leg. 3) Swimming exercise; anabolic steroid; swimming and anabolic steroid; normal exercise control. Traits measured were body weight gain and thirteen femoral characters: moment at failure, length, cross-sectional area, anteroposterior and lateromedial diameters of the cross section, wall thickness for all four quadrants of the shaft, moments of inertia of the cross section in the anteroposterior and lateromedial directions, deflection of the shaft before failure, and total mineral content. Sexual dimorphism of the traits studied varied significantly with treatment. The greatest dimorphism was seen in the controls and the burrowing group. The least dimorphism was seen in the eight times gravity, the steroid, and the exercise and anabolic steroid groups. Reduction in the extent of sexual dimorphism was not correlated with a reduction in the loading regimen but rather seemed mediated by systemic changes in physiology brought on by several factors. Change in the amount of sexual dimorphism for size from the control reflects change in growth rates for males and females in response to different treatments. Change in growth rates of juvenile males and females will likely result in changes in the size of femoral characters and body weight in the adult. Change in the size of femoral characters affects the strength of the femur. In natural populations, a change in the body size of adult males and females could adversely affect reproductive success in groups that normally exhibit strong dimorphism, and hence, select against any conditions that reduce sexual dimorphism. Ordinarily, a significant change in sexual dimorphism--of the magnitude seen here--through natural selection, would take several generations.
Animals↗