Leptin and cytokines levels in children with failure to thrive

BACKGROUND: The majority of cases of failure to thrive (FTT) are non-organic. Many of these patients present with significant decreased caloric intake. It appears as if the appetite regulation center in the hypothalamus is not attuned to the calorie requirements of the infant. OBJECTIVE: Our hypothesis was that some cases of non-organic FTT might be caused by abnormalities in hunger/satiety control secondary to neuroendocrine or cytokine imbalance. The aim of this study was to investigate which hormonal/cytokine profiles could be assigned to a defined category of FTT, namely organic, psychosocial and idiopathic subgroups. STUDY DESIGN: 34 patients were enrolled and 32 completed the study (12 controls, 12 idiopathic FTT, 5 organic FTT, and 3 psychosocial FTT). Each child was assessed by a pediatric gastroenterologist, dietician, and social worker and underwent appropriate laboratory investigation during which leptin, IL1, IL6 and TNF-alpha levels were determined. The Mann-Whitney U test was used to compare the groups. RESULTS: IL6 was the only cytokine that showed significant differences between FTT patients (4.06 +/- 6.3 pg/ml) and normal controls (0.0 pg/ml (p = 0.028). Leptin values were significantly higher in the normal control group (1632 +/- 483 pg/ml) as compared to FTT patients (685 +/- 687 pg/ml) (p = 0.001). CONCLUSIONS: Our results indicate that leptin does not play a role in the pathogenesis of anorexia in children with FTT. It is however, possible that IL6 may be an important factor in the etiology of anorexia in patients with FTT.     

Gamma-delta T-cell phenotype is associated with significantly decreased survival in cutaneous T-cell lymphoma

The importance of alpha beta versus gamma delta T-cell subset antigen expression in the classification of peripheral T-cell lymphomas is still unclear. The objective of this study was to investigate the prognostic value of T-cell receptor-delta 1 (TCR delta 1) expression in primary cutaneous T-cell lymphomas. TCR delta 1 cellular expression was assessed in skin biopsy specimens of 104 individuals with cutaneous T-cell lymphoma by immunohistochemistry. Both univariate (Kaplan-Meier) and multivariate (Cox regression) analyses were conducted to determine which variables (T-cell subtype, hemophagocytosis, histologic profile, age, sex, and adenopathy) were significantly associated with survival. Univariate analysis indicated that there was a statistically significant difference in survival between the patients with alpha beta cutaneous T-cell lymphoma and patients with gamma delta cutaneous T-cell lymphoma (P <.0001). There was also a statistically significant decrease in survival among patients who had subcutaneous involvement compared with patients who had epidermotropic and/or dermal involvement (P <.0001). Cox model analysis indicated that TCR delta 1 expression was the factor that was most closely associated with decreased survival (P <.0001). Among those patients with cutaneous gamma delta T-cell lymphoma (n = 33), there was a trend for decreased survival for patients who had histologic evidence of subcutaneous fat involvement in comparison with patients who had epidermotropic or dermal patterns of infiltration (P =.067). No other prognostic factors were identified as having a notable association with outcome in this subgroup. TCR delta 1 expression in primary cutaneous lymphomas is an independent prognostic factor associated with decreased survival.     

Impact of antimicrobial resistance on health outcomes in the out-patient treatment of adult community-acquired pneumonia: a probability model

Out-patient treatment of community-acquired pneumonia (CAP) is a major challenge in an era of increasing prevalence of antimicrobial resistance. However, data describing the clinical impact of such resistance are scarce. A probability model was developed to estimate the impact of antimicrobial resistance on clinical outcomes for adults with CAP, eligible for out-patient care. The model assumed patients would be evaluated at 48-72 h, with those failing to improve being either hospitalized or switched to a different antibiotic. Two strategies were considered: amoxicillin followed by erythromycin (amoxicillin/erythromycin) and erythromycin followed by levofloxacin (erythromycin/levofloxacin). Analyses were conducted based on susceptibility of the major pathogens in France and the UK. Primary model-generated outcome measures were the proportion of patients successfully treated with first-line therapy and the proportion of patients subsequently hospitalized. The model estimated that in France, the amoxicillin/erythromycin strategy would lead to 67.8% improving within 48-72 h and 12.7% subsequently being hospitalized, compared with 48.6% and 13.7% for erythromycin/levofloxacin. For the UK, first-line success and hospitalization rates were, respectively, 71.7% and 8.1% for amoxicillin/erythromycin, and 65.3% and 9.3% for erythromycin/levofloxacin. The model estimated that antimicrobial resistance was responsible for >40% of hospitalizations in France and 15% in the UK. These data suggest that in areas with substantially reduced levels of susceptibility, antimicrobial resistance may be a significant contributor to subsequent hospitalization in adults initially treated as out-patients for CAP. Choice of out-patient treatment strategy should consider local resistance rates in order to maximize the likelihood of early cure, thereby minimizing hospitalizations.     

Single and multiple metachronous osteosarcoma tumors after therapy

BACKGROUND: The objective of the current study was to determine the incidence, clinical and pathologic characteristics, and outcome of patients with conventional osteosarcoma who developed metachronous tumors after treatment for the primary tumor and prevention of pulmonary metastases. METHODS: The medical records of 270 pediatric patients (younger than age 18 years) were reviewed. The prevention and absence of pulmonary metastases was confirmed by chest radiographs and computerized scans of the lungs. Radionuclide bone scans were used to confirm the absence of skeletal metastases. RESULTS: Eleven patients with metachronous tumors were identified. Index primary tumors involved the femur (n = 8), the tibia (n = 2), and the radius (n = 1). Single metachronous tumors developed in the femur (n = 6), in the humerus (n = 1), and multifocal in multiple bones (n = 4). Two patients later developed second metachronous tumors. The interval between identification of the primary tumor to development of the single metachronous tumors varied from 11 months to 78 months and from 12 months to 42 months for synchronous multifocal tumors. Metachronous tumors were treated with single-agent cisplatin or ifosfamide. Only 1 patient experienced > 90% tumor necrosis. Pulmonary metastases were not detected in 10 of 11 patients at the time metachronous tumors were discovered. In the 11th patient, synchronous pulmonary metastasis with the metachronous tumor was noted. Three patients had a prior history of bilateral retinoblastoma. The Li-Fraumeni syndrome may have been present in another patient. Six patients died. Five patients have survived for 20+ to 50+ months after the appearance, treatment, and resection of metachronous tumors. CONCLUSIONS: With improvement in the cure rate, metachronous osteosarcoma should be recognized as an important sequela in long-term survivors. The etiology of this disease is unknown. Speculation rests on a skeletal multicentric origin, which includes an inherited predisposition to develop osteosarcoma in retinoblastoma and in the Li-Fraumeni syndrome. Meticulous follow-up is required to permit early detection and successful therapeutic intervention.     

Use of a fibular allograft strut in the treatment of benign lesions of the proximal femur

Fifteen patients with a benign lesion of the proximal femur were surgically treated with augmented intralesional curettage and bone grafting using an allogenic fibular strut graft in conjunction with internal fixation with a sliding hip screw. Mean age was 26 years (range, 13-46 years). Patients were followed up for a mean of 30 months (range, 7-110 months). Clinical results were assessed using the functional-evaluation-of-reconstruction procedures described by the Musculoskeletal Tumor Society. Radiographic outcomes were assessed by comparing preoperative radiographs with radiographs taken at the most recent follow-up. Clinical results were excellent in all patients. Radiographic assessment of the patients showed no evidence of recurrent tumor, fracture, or graft resorption at the most recent follow-up. This method of treatment leads to excellent functional results and lessens the morbidity associated with autograft harvest.     

The need for voiding diaries in the evaluation of men with nocturia

In a study to assess the need for voiding diaries in the evaluation of men with nocturia, 337 consecutive male patients were asked to estimate their number of voiding episodes per night. Patients were placed into seven separate groups based on the number of estimated number of voiding episodes. These patients used a voiding diary to track their voiding habits for 1 week. The mean number of voiding episodes recorded in the diaries were then compared with the subjects' original estimations. The estimated number of voiding episodes correlated with the mean number of diary-recorded voiding episodes 48% of the time. Correlation was highest for patients reporting few episodes per evening and lowest for those reporting five or six episodes per night. The study findings suggest that voiding diaries are essential in helping to determine the actual number of voiding episodes per night and that the need for a voiding diary becomes more important as the perceived amount of nocturia increases.     

In situ localization of follicular lymphoma: description and analysis by laser capture microdissection

From 1992 to 2000, we identified 23 lymph node biopsies with focal germinal centers (GCs) containing centrocytes staining strongly for bcl-2 protein, whereas most of the remaining lymph node showed bcl-2-negative follicular hyperplasia. We propose the designation in situ localization of follicular lymphoma (FL) for this phenomenon. In 2 additional cases, bcl-2(+) follicles with features of in situ FL were identified in association with other low-grade B-cell lymphomas. To investigate the clonality of the bcl-2(+) follicles, we performed laser capture microdissection of bcl-2(+) and bcl-2 follicles from the same lymph node in 5 cases, and analyzed them in parallel by polymerase chain reaction (PCR) amplification of immunoglobulin heavy chain (IgH) genes. In 4 of 5 cases the bcl-2(+) follicles contained monoclonal IgH gene rearrangements, whereas the bcl-2(-) GCs exhibited a polyclonal ladder. A BCL2/JH gene rearrangement was detected in 6 of 14 (43%) evaluable cases. There were 5 patients with synchronous evidence of FL at another site. There were 13 patients who, without a prior diagnosis of FL, had clinical follow-up; one developed FL in an adjacent lymph node within one year, and 2 manifested FL at 13 and 72 months, respectively. There are 10 patients who have not yet shown other evidence of FL. These results suggest that at least close to half of these cases (8/18; 44%) represent homing to and early colonization of reactive GCs by FL. Other cases might represent FL at the earliest stage of development, or a preneoplastic event, requiring a second hit for neoplastic transformation. These findings provide insight into the pathophysiology of early FL, and illustrate the utility of immunohistochemistry for early diagnosis.     

Rationale and methods for the National Tuberculosis Genotyping and Surveillance Network

Our understanding of tuberculosis (TB) transmission dynamics has been refined by genotyping of Mycobacterium tuberculosis strains. The National Tuberculosis Genotyping and Surveillance Network was designed and implemented to systematically evaluate the role of genotyping technology in improving TB prevention and control activities. Genotyping proved a useful adjunct to investigations of outbreaks, unusual clusters, and laboratory cross-contamination.     

Effect of INS37217, a P2Y(2) receptor agonist,on experimental retinal detachment and electroretinogram in adult rabbits

PURPOSE: To evaluate the effects of subretinal and intravitreal delivery of INS37217, a P2Y(2) receptor agonist, on subretinal fluid reabsorption in experimentally induced retinal detachments in rabbits, and to characterize the effects of INS37217 on electroretinograms (ERG) in rabbits. METHODS: A single retinal detachment was produced in New Zealand White rabbits by injecting approximately 50 micro L of modified phosphate-buffered saline (MPBS) solution into the subretinal space (SRS). In all experiments, one eye served as the INS37217-treated eye and the contralateral eye served as the vehicle control. In the first series of experiments, each rabbit received a SRS injection of MPBS solution, with or without INS37217 (1 mM). In the second series of experiments, each eye received an SRS injection of MPBS solution, followed by an intravitreal injection of MPBS solution, with or without INS37217 (12, 1.4, and 0.15 mM). A masked observer determined the size of blebs by indirect ophthalmoscopy at 30-minute intervals for up to 3 hours after SRS injections. Optical coherence tomography (OCT) was conducted to provide cross-sectional images of the blebs. Cellular expression of P2Y(2) receptor mRNA was localized by nonradioisotopic in situ hybridization in fresh rabbit retina-RPE tissue sections. Bilateral, full-field scotopic and photopic ERGs were made at 1, 7, and 14 days after a single intravitreal injection of 24 mM INS37217. RESULTS: SRS administration of 1 mM INS37217 significantly enhanced subretinal fluid reabsorption when compared with vehicle controls (P < 0.05; repeated measures ANOVA). Intravitreal administration of INS37217 at 12 and 1.4 mM, but not at 0.15 mM, also significantly enhanced subretinal fluid reabsorption (P < 0.05). P2Y(2) receptor mRNA was observed throughout the RPE and in discrete layers of the retina. INS37217 had no adverse effects on scotopic and photopic ERG amplitude and latency parameters at any of the postadministration time points evaluated. CONCLUSIONS: These results demonstrate that INS37217 enhances subretinal fluid reabsorption in experimental retinal detachment in rabbits and support the development of INS37217 for stimulating subretinal fluid reabsorption in conditions that result in retinal detachment or retinal edema.