Nutritional rickets with normal circulating 25-hydroxyvitamin D: a call for reexamining the role of dietary calcium intake in North American infants

The incidence of nutritional rickets appears to be increasing in North American infants and toddlers; it is widely assumed that this is due to vitamin D deficiency. Thus, records of 43 children with nutritional rickets from greater New Haven, Connecticut, from 1986-2002 were identified. The mean age of presentation was 20 months; 86% were of African-American, Hispanic, or Middle Eastern descent. More than 93% of children had been breastfed; however, 15% had received vitamin D supplementation. Eighty-six percent of those with food histories available were weaned to diets with minimal dairy content after nursing. Serum 25-hydroxyvitamin D was 20.9 +/- 11.5 ng/ml and was less than 15 ng/ml in only 22% of patients. Three representative case histories suggest that dietary calcium intake may play a contributory role in the development of disease; 1 case documents radiographic and biochemical resolution of rachitic abnormalities after calcium treatment, but no vitamin D therapy. Clinicians should be aware that low dietary calcium intake after weaning may result in the development of nutritional rickets, and that attention to calcium intake as well as that of vitamin D is important in the establishment of optimal dietary practices for North American infants and children.     

The cell surface form of colony-stimulating factor-1 is biologically active in bone in vivo

The specific biological function of the cell surface or membrane-bound isoform of colony-stimulating factor-1 (mCSF-1) is not well understood. To help define the role of this isoform in bone, we developed a transgenic mouse in which targeted expression of human mCSF-1 in osteoblasts was achieved under the control of the 2.4-kb rat collagen type I alpha promoter. Bone density, determined by peripheral quantitative computed tomography, was reduced 7% in mCSF-1 transgenic compared with that in wild-type mice. Histomorphometric analyses indicated that the number of osteoclasts in bone (NOc/BPm, NOc/TAR, OcS/BS) was significantly increased in transgenic mice (1.7- to 1.8-fold; P < 0.05 to P < 0.01) compared with that in wild-type animals. Interestingly, the osteoblast-restricted isoform transgene corrected the osteopetrosis seen in CSF-1-deficient op/op mice. Skeletal growth and bone density in op/op mice expressing mCSF-1 in osteoblasts were similar to those in wild-type mice and were dramatically different from those in the unmanipulated op/op animals. The op/op mice expressing mCSF-1 in bone had normal incisor and molar tooth eruption, whereas the op/op mice evidenced the expected failure of tooth eruption. These findings directly support the conclusion that mCSF-1 is functionally active in bone in vivo and is probably an important local source of CSF-1.     

Neuroimaging abnormalities in children with an apparent first unprovoked seizure

OBJECTIVE: To determine the incidence and type of neuroimaging abnormalities in children presenting with a first seizure. METHODS: In a prospective observational study, 411 children with a first afebrile seizure were seen between 1983 and 1992. Imaging studies were performed in 218 (53%). For this analysis we examined the most sensitive neuroimaging study performed which included 159 computed tomography scans and 59 magnetic resonance imagings (MRI). RESULTS: Four children were found to have lesions requiring intervention (brain tumor in two, neurocysticercosis in two). The remaining 407 were enrolled in a follow-up study of children with a first unprovoked seizure. After a mean follow-up of >10 years, none have developed clinical evidence of a tumor. In these 411 children, 45 (21%) of 218 imaging studies were abnormal. The most common abnormalities were focal encephalomalacia (n=16) and cerebral dysgenesis (n=11). Although children with partial seizures were more likely to be imaged (64%) than children with generalized seizures (43%) (P<0.001), the fraction of abnormal imaging studies was similar in both groups. Six children with a normal neurological examination who were initially classified as cryptogenic were subsequently found to have errors of cerebral migration on MRI. The incidence of lesions requiring acute intervention in children presenting with a first seizure is low. A significant proportion will have neuroimaging abnormalities particularly on MRI. CONCLUSIONS: Neuroimaging should be considered in any child with a first seizure who does not have an idiopathic form of epilepsy.     

Patterns of central nervous system recurrence in patients with systemic human immunodeficiency virus-associated non-hodgkin lymphoma.

BACKGROUND: Central nervous system involvement is a common manifestation of non-Hodgkin lymphoma (NHL) in human immunodeficiency virus (HIV)-infected individuals. The purpose of this study was to review the frequency and pattern of neurologic manifestation of lymphoma in a cohort of HIV-infected individuals with systemic NHL. METHODS: Sixty-two patients with HIV-associated systemic NHL received infusional cyclophosphamide, doxorubicin, and etoposide. Five patients with lymphomatous meningitis at presentation received whole brain radiation therapy plus intrathecal chemotherapy (ITC). Of the remaining 57 patients, prophylactic ITC was recommended only for those patients with lymphomatous bone marrow involvement and/or high grade histology (N = 31). RESULTS: Thirteen patients (21%) had histologically documented (N = 6) or presumed (N = 7) central nervous system involvement, including 7 patients (11%) with meningeal lymphoma discovered either at presentation (N = 5) or soon after diagnosis (N = 2), and 6 patients (10%) with cerebral mass lesions at the time of disease recurrence consistent with parenchymal brain involvement. Five of six parenchymal brain recurrences occurred in the setting of progressive systemic disease. Four of 7 patients (57%) with meningeal lymphoma detected at presentation (N = 5) or within 3 months of presentation (N = 2) responded to therapy and survived >1 year. Of the 26 patients assigned to receive no prophylactic ITC, no patient developed an isolated meningeal recurrence and 1 patient developed an isolated parenchymal brain recurrence. CONCLUSIONS: The findings of the current study suggest that in patients with HIV-associated systemic lymphoma, meningeal lymphoma is potentially curable, parenchymal brain recurrence usually occurs in the setting of uncontrolled systemic disease, and prophylactic ITC may not be necessary for patients with intermediate grade histology and uninvolved bone marrow.     

Variability of Gross Tumor Volume Delineation in Head-and-Neck Cancer Using PET/CT Fusion,Part II: The Impact of a Contouring Protocol

The purpose of this study was to assess the efficacy of a gross tumor volume (GTV) contouring protocol on interobserver variability between 4 physicians in positron emission therapy/computed tomography (PET/CT) treatment planning of head-and-neck cancer. A GTV contouring protocol for PET/CT treatment planning was developed utilizing 4 stages: Preliminary contouring on CT alone, determination of appropriate PET windowing, accurate image registration, and modification of CT contouring with correctly formatted PET/CT display and rules for modality disagreement. Two neuroradiologists and 2 radiation oncologists (designated as A, B, C, and D, respectively) were given a tutorial of PET/CT coregistered imaging individualized to their skill level, which included a step-by-step explanation of the protocol with clinical examples. Opportunities for questions and hands-on practice were given. The physicians were asked to re-contour 16 head-and-neck patients from Part I on PET/CT fusion imaging. Differences in volume magnitude were analyzed for statistical significance by analysis of variance (ANOVA) and paired t-tests (α < 0.05). Volume overlap was analyzed for statistical significance using Wilcoxon signed-rank tests (α < 0.05). Volume overlap increased significantly from Part I to Part II (p < 0.05). One previously significant difference between physicians disappeared with the protocol in place. The mean fusion volume of Physician C, however, remained significantly larger than that of Physician D (p < 0.01). This result is unchanged from Part I. The multidisciplinary contouring protocol significantly improved the coincidence of GTVs contoured by multiple physicians. The magnitudes of the volumes showed marginal improvement in consistency. Developing an institutional contouring protocol for PET/CT treatment planning is highly recommended to reduce interobserver variability.     

Circumscribed intraductal carcinoma of the breast

In a retrospective evaluation of 350 cases of proved intraductal carcinoma detected over a 3-year period, 13 had mammographic features similar to those of benign tumors. The carcinomas were sharply circumscribed, round or oval lesions that contained microcalcifications. These calcifications were smaller and more likely to be asymmetrically located within the nodule than those of the fibroadenomas that they mimicked. While the carcinomas appeared circumscribed on mammograms, microinvasion of surrounding tissue was proved histologically in five of 13 cases, and in another case biopsy revealed metastasis to an axillary lymph node. Although these carcinomas are relatively rare, mammographic detection is important as none were palpable at the time of diagnosis.     

Systemic lupus erythematosus: an overview

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease of unknown etiology in which the normal immune responses are directed against healthy organs and tissues. The disregulated immune system produces antibodies that attack the skin, joints, kidneys, heart, and brain. Some people experience mild rashes and arthritis, others suffer debilitating fever, fatigue, joint pain, and severe organ and/or life-threatening disease. This article provides a medical overview of the epidemiology of SLE, the challenges of diagnosing SLE, the complexity of the clinical manifestations and treatment issues, and the impact of SLE on patients' lives. We also discuss the progress in understanding the disease and its therapy over the last century.