Unrecognized visual field deficits in children with primary central nervous system brain tumors.

Visual field deficits can be a consequence of brain tumor location or treatment. The prevalence of unrecognized visual field deficits in children diagnosed with brain tumors is not known. All children at a single tertiary care pediatric children's hospital diagnosed with a primary brain tumor were tested for visual field deficits by a child neurologist and neuro-ophthalmologist over 16 months. Children with reproducible visual field deficits on two separate occasions were included in the analysis. Patients with optic glioma, craniopharyngioma, or previously known visual field deficits were excluded. Fourteen of 92 (15.2%) children (average 8.9 years, 8 girls) had undiagnosed visual field deficits. Average time between diagnosis of tumor and unrecognized visual field deficit was 3.7 years (range 0-13 years). Unrecognized visual field deficits were not associated with age (P = 0.27) or gender (P = 0.38). Visual field deficits were attributed to direct tumor infiltration (n = 8), postoperative complications (n = 5) and post-radiation edema (n = 1). Deficits included bitemporal hemianopsia (n = 2), homonymous hemianopsia (n = 9), quadrantanopsia (n = 2), and concentric visual field loss (n = 1.) Tumor location included temporal lobe (n = 9), parietal lobe (n = 2), posterior fossa (n = 2), hypothalamic-chiasmatic (n = 2) and multifocal areas (n = 4). Children with temporal lobe tumors were more likely to have unrecognized visual field deficits (P = 0.004). In all 14 patients, visual field deficits were determined by examination only and were not reported by either the patient or caregiver regardless of age. The prevalence of unrecognized visual field deficits in children with brain tumors can be surprisingly high. Serial neuro-ophthalmologic evaluation of children with brain tumors is often required to diagnose a visual field deficit since patient or caregiver reporting may be limited.

Properties of the COPD assessment test in a cross-sectional European study.

A short, easy-to-use health status questionnaire is needed in the multidimensional assessment of chronic obstructive pulmonary disease (COPD) in routine practice. The performance of the eight-item COPD assessment test (CAT) was analysed in 1,817 patients from primary care in seven European countries. The CAT has a scoring range of 0-40 (high score representing poor health status). Mean CAT scores indicated significant health status impairment that was related to severity of airway obstruction, but within each Global Initiative for Obstructive Lung Disease stage (I to IV) there was a wide range of scores (I: 16.2 ± 8.8; II: 16.3 ± 7.9; III: 19.3 ± 8.2; and IV: 22.3 ± 8.7; I versus II, p = 0.88; II versus III, p<0.0001; III versus IV, p = 0.0001). CAT scores showed relatively little variability across countries (within ± 12% of the mean across all countries). Scores were significantly better in patients who were stable (17.2 ± 8.3) versus those suffering an exacerbation (21.3 ± 8.4) (p<0.0001); and in patients with no (17.3 ± 8.1) or one or two (16.6 ± 8.2) versus three or more (19.7 ± 8.5) comorbidities (p<0.0001 for both). The CAT distinguished between classes of other impairment measures and was strongly correlated with the St George's Respiratory Questionnaire (r = 0.8, p<0.0001). The CAT is a simple and easy-to-use questionnaire that distinguishes between patients of different degrees of COPD severity and appears to behave the same way across countries.

A new perspective on concepts of asthma severity and control.

Concepts of asthma severity and control are important in the evaluation of patients and their response to treatment but the terminology is not standardised and the terms are often used interchangeably. This review, arising from the work of an American Thoracic Society/European Respiratory Society Task Force, identifies the need for separate concepts of control and severity, describes their evolution in asthma guidelines and provides a framework for understanding the relationship between current concepts of asthma phenotype, severity and control. "Asthma control" refers to the extent to which the manifestations of asthma have been reduced or removed by treatment. Its assessment should incorporate the dual components of current clinical control (e.g. symptoms, reliever use and lung function) and future risk (e.g. exacerbations and lung function decline). The most clinically useful concept of asthma severity is based on the intensity of treatment required to achieve good asthma control, i.e. severity is assessed during treatment. Severe asthma is defined as the requirement for (not necessarily just prescription or use of) high-intensity treatment. Asthma severity may be influenced by the underlying disease activity and by the patient's phenotype, both of which may be further described using pathological and physiological markers. These markers can also act as surrogate measures for future risk.

Autoantibodies in Caribbean youth with diabetes mellitus.

The prevalence of diabetes and other autoantibodies in patients with recently diagnosed youth onset diabetes was evaluated. Fifty-seven patients (95% black, age 19 +/- 5 years, 36% male, diabetes duration 2.6 +/- 2.2 years) were clinically diagnosed as having type 1 (n = 35), type 2 (n = 13) and lipoatrophic diabetes (n = 3) while 6 remained untyped. GAD65 was the most common diabetes-associated autoantibody in patients with type 1A diabetes (12/17; 71%). The prevalence of any diabetes-associated autoantibodies decreased with diabetes duration (OR[95%CI]/yr after diagnosis 0.50[0.31,0.82]) and was not associated with age of onset, duration or gender. Rheumatoid factor (13/57; 23%), smooth muscle (6/57; 11%), gastric-parietal cell (5/57; 9%) and thyroid microsomal antibodies (5/57; 9%) were the most frequent non-diabetes associated autoantibodies and were more common in patients with type 1A diabetes. Only one patient had clinical autoimmune disease (hypothyroidism). Type 1A diabetes may constitute up to half the cases of newly diagnosed type 1 diabetes in Jamaican youth and is associated with a higher prevalence of other organ-specific autoantibodies.

Survivin as a therapeutic target in Sonic hedgehog-driven medulloblastoma.

Medulloblastoma (MB) is a highly malignant brain tumor that occurs primarily in children. Although surgery, radiation and high-dose chemotherapy have led to increased survival, many MB patients still die from their disease, and patients who survive suffer severe long-term side effects as a consequence of treatment. Thus, more effective and less toxic therapies for MB are critically important. Development of such therapies depends in part on identification of genes that are necessary for growth and survival of tumor cells. Survivin is an inhibitor of apoptosis protein that regulates cell cycle progression and resistance to apoptosis, is frequently expressed in human MB and when expressed at high levels predicts poor clinical outcome. Therefore, we hypothesized that Survivin may have a critical role in growth and survival of MB cells and that targeting it may enhance MB therapy. Here we show that Survivin is overexpressed in tumors from patched (Ptch) mutant mice, a model of Sonic hedgehog (SHH)-driven MB. Genetic deletion of survivin in Ptch mutant tumor cells significantly inhibits proliferation and causes cell cycle arrest. Treatment with small-molecule antagonists of Survivin impairs proliferation and survival of both murine and human MB cells. Finally, Survivin antagonists impede growth of MB cells in vivo. These studies highlight the importance of Survivin in SHH-driven MB, and suggest that it may represent a novel therapeutic target in patients with this disease.

Prenatal diagnosis of dominant and recessive dystrophic epidermolysis bullosa: application and limitations in the use of KF-1 and LH 7:2 monoclonal antibodies and immunofluorescence mapping technique.

Prenatal diagnosis is now possible for junctional and recessive dystrophic forms of epidermolysis bullosa (EB); however, there is no similar published experience for dominant dystrophic EB, although data with KF-1 monoclonal antibody suggests that both forms of dystrophic EB can be identified at least postnatally with this unique probe. We now report our experience with light microscopy, electron microscopy, immunofluorescence mapping, and KF-1 and LH 7:2 monoclonal antibodies, in both a mother with dominant dystrophic EB and her fetus at risk, and in a fetus previously shown to be affected with recessive dystrophic EB. KF-1 and LH 7:2 antigens were absent in recessive dystrophic EB fetal skin, identical to findings observed postnatally. LH 7:2 was normally expressed in a mother with dominant dystrophic EB and in her fetus at risk for this disease. In contrast, while KF-1 antigen was abnormally expressed in the affected mother, it was normally expressed in only 1/7 fetal biopsies despite the fact that this fetus was shown by light and electron microscopy and immunofluorescence mapping to be unaffected with dominant dystrophic EB. We conclude that 1) transmission electron microscopy can be used to prenatally exclude the diagnosis of dominant dystrophic EB (Cockayne-Touraine variety), 2) immunofluorescence mapping is an accurate technique for prenatal as well as postnatal diagnosis of EB, and 3) KF-1 cannot by itself be used as an accurate probe for the prenatal diagnosis of dominant dystrophic EB, due to the apparent variability in the time for the normal expression of KF-1 in fetal skin during the second trimester.

Apolipoprotein E genotype and noncognitive symptoms in Alzheimer's disease.

BACKGROUND: The apolipoprotein E (ApoE) epsilon 4 allele confers significant risk for Alzheimer's disease and is associated with a greater amyloid burden in the brain. Future treatments may target molecular mechanisms associated with this allele, and it is important to define any phenotypic characteristics that correspond to this genotype. We sought to clarify the relationship between ApoE status and noncognitive symptoms in Alzheimer's disease patients. METHODS: Possible and probable Alzheimer's disease patients from a clinical trial (n = 605) were assessed with the 10-item Neuropsychiatric Inventory cross-sectionally prior to treatment, and their ApoE genotype was determined. Among the population studied, the following numbers with specific genotypes were studied: 23-2/3, 17-2/4, 209-3/3, 288-3/4, 68-4/4. RESULTS: When correlations were controlled for the patient's level of cognitive impairment, there was no relationship between epsilon 4 dose and any of the 10 noncognitive symptoms assessed, including psychosis, mood changes, and personality alterations. CONCLUSIONS: Among patients with comparable disease severity, the epsilon 4 allele does not confer additional psychiatric morbidity.

Longitudinal assessment of symptoms of depression, agitation, and psychosis in 181 patients with Alzheimer's disease.

OBJECTIVE: The goal of this study was to define the recurrence or continuation of neuropsychiatric symptoms in patients with Alzheimer's disease who were observed serially for a 1-year period. METHOD: One hundred eighty-one patients with probable Alzheimer's disease were assessed five times at 3-month intervals with a standardized neuropsychiatric rating instrument. RESULTS: Recurrence rates of neuropsychiatric symptoms during the 1-year period were 85% for depression, 93% for agitation, and 95% for psychosis. Symptom frequency at any point in time underestimated the cumulative 1-year frequency. Recurrence rates were significantly greater among patients who had multiple symptoms. Women exhibited more symptoms than men. Patients in the oldest age group (76-87 years) had more psychosis, less depression and agitation, and slower cognitive decline. Psychosis was associated with more rapid cognitive decline, and agitation was associated with more rapid functional deterioration. CONCLUSIONS: These results indicate that once psychiatric symptoms are present in patients with Alzheimer's disease, they frequently recur. These symptoms vary with age, sex, and rate of illness progression.

Alzheimer disease and frontotemporal dementias. Behavioral distinctions.

BACKGROUND: Frontotemporal dementia (FTD) is a syndrome produced by lobar degeneration of the temporal and/or frontal lobes. OBJECTIVES: To quantify the behavioral disturbances of FTD and compare them with behavioral changes observed in Alzheimer disease (AD). DESIGN: Cross-sectional comparison of 2 groups defined by research diagnostic criteria and single photon emission computed tomography. Behaviors were assessed using a standardized rating scale-Neuropsychiatric Inventory. Groups were matched for dementia severity. SETTING: Patients were seen at 2 university-based outpatient dementia clinics and a Veterans Affairs medical center. PARTICIPANTS: Twenty-two patients with FTD and 30 patients with AD. RESULTS: Patients with FTD had significantly greater total Neuropsychiatric Inventory scores than patients with AD and exhibited more apathy, disinhibition, euphoria, and aberrant motor behavior. The Neuropsychiatric Inventory accurately assigned 77% of patients with FTD and 77% of patients with AD to the correct diagnostic group using disinhibition, apathy, and depression. Patients with FTD had higher levels of disinhibition and apathy with relatively lower levels of depression compared with patients with AD. CONCLUSIONS: The Neuropsychiatric Inventory provides a behavioral profile that differentiates patients with FTD from patients with AD. Patients with FTD are more behaviorally disturbed but are often less depressed than patients with AD relative to their level of apathy.

Invasive fungal dermatitis in the < or = 1000-gram neonate.

OBJECTIVE: In 1991, we noted the emergence amongst our extremely low birth weight neonates of a new clinical entity, invasive fungal dermatitis, characterized by erosive, crusting lesions and a high rate of subsequent systemic fungal infection. We sought to define this condition and examine potential risk factors. METHODS: Sixteen neonates with invasive fungal dermatitis were seen during a 2-year period in three Baylor College of Medicine affiliated intensive care nurseries. Seven were confirmed cases, with skin biopsy evidence of invasion beyond the stratum corneum. Nine had a consistent clinical course and a positive potassium hydroxide examination of skin scrapings or isolation of fungi from skin or systemic cultures. Three controls were matched to each case by hospital, date of admission, and birth weight. Data was collected by retrospective chart review. RESULTS: Invasive fungal dermatitis occurred in 5.9% of at-risk infants. Case patients had a mean birth weight of 635 g and developed skin lesions at a mean age of 9 days (range, 6 to 14). Candida albicans was the most commonly implicated pathogen, but other Candida species, Aspergillus, Trichosporon beigelii, and Curvularia were also seen. Disseminated infection occurred in 69%, all due to Candida sp. Case patients were significantly more premature than controls (mean gestation, 24.4 vs 25.9 weeks) and were more likely to be delivered vaginally (81% vs 50%). Postnatal steroids were administered to cases (81%) more often than controls (46%). Case patients had more prolonged hyperglycemia (as assessed by insulin administration) than controls (mean 4.3 vs 2.0 days). CONCLUSIONS: Invasive fungal dermatitis is a disease of the smallest, most immature neonates and is associated with vaginal birth, steroid administration, and hyperglycemia. We speculate that the skin serves as a portal of entry for colonizing fungal species and may thus lead to disseminated infection. Methods to improve skin barrier function may be useful in preventing this disorder.

Schöpf-Schulz-Passarge syndrome with an unusual pattern of inheritance.

Schöpf-Schulz-Passarge syndrome is a rare form of ectodermal dysplasia comprising hypotrichosis, hypodontia, unusual eyelid cysts, palmar-plantar keratosis, and nail dystrophy. To date, ten cases have been reported; all except one are compatible with autosomal recessive inheritance. We report on a family in which three full sibs and one half-sib have Schopf-Schulz-Passarge syndrome, yet there is no other evidence of dominant transmission in prior or subsequent generations. Possible explanations are discussed.

Clinical manifestations in a cohort of 41 Rothmund-Thomson syndrome patients.

Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive genodermatosis characterized by a poikilodermatous rash starting in infancy, small stature, skeletal abnormalities, juvenile cataracts, and predisposition to specific cancers. We have identified a contemporary cohort of 41 patients to better define the clinical profile, diagnostic criteria, and management of patients with RTS. Patients with the diagnosis of RTS were ascertained by referrals from dermatology, ophthalmology, genetics, and oncology or from direct contact with the patient's family. Medical information was obtained from interviews with physicians, patients, and their parents and a review of medical records. The age range at ascertainment was 9 months to 42 years (28 males and 13 females; M:F, 2:1). All subjects displayed a characteristic rash. Thirteen subjects had osteosarcoma (OS) (32%), eight had radial defects (20%), seven had gastrointestinal findings (17%), two had cataracts (6%), and one had skin cancer (2%). Twenty-two of 28 patients without OS were less than 15 years old and thus remain at significant risk for this tumor. This case-series study reveals a clinical profile of RTS that includes a higher prevalence of OS and fewer cataracts, compared with historical reports. These differences may reflect either allelic or genetic heterogeneity. This study documents the frequency of clinical anomalies in a contemporary cohort of RTS patients and revises guidelines for diagnosis and management of RTS.

The ringworm riddle: an outbreak of Microsporum canis in the nursery.

Tinea capitis, the most common fungal infection in children, is rare in neonates. We report six patients in a Level II intermediate care nursery who developed nosocomial dermatophyte infections caused by Microsporum canis. The investigation, which led to the identification of a nurse as the common source, is described. The nurse had an indolent infection with M. canis. Human to human transmission is exceedingly rare for M. canis. The literature regarding neonatal dermatophyte infections is discussed in relation to the reported outbreak.

The role of adrenergic stimulation in the pathogenesis of pulmonary insufficiency.

Recent studies have shown that epinephrine (E), norepinephrine (NE), and isoproterenol (I) caus'e substantial pulmonary shunting. This study was undertaken to determine the role of alpha (pulmonary vasconconstriction) and beta (pulmonary vasodilatation) adrenergic stimulation in the pathogenesis of pulmonary insufficiency. Forty-three mechanically ventilated, anesthetized dogs received infusions of E, alpha and beta stimulant; NE, a relatively pure alpha stimulant; I, a relatively pure beta stimulant; and dextran (D), a drug with no known adrenergic activity. The cardiac output and shunt measurements were determined simultaneously in the control period and four times during a 1 hour infusion. The quadratic equation of best fit was determined for each group for the relationship between the cardiac output and the shunt over a wide range of cardiac outputs, and statistical comparisons were made between all groups of the shunt at the same cardiac output. In all groups an increase in cardiac output was associated with an increase in the shunt, but the magnitude of the increase in the shunt differed significantly with each drug over the entire range, being smallest with D and becoming progressively larger with I, E, and NE, respectively. It is concluded that an increase in the pulmonary blood flow causes an increase in the pulmonary shunt, but that the magnitude of the increase is dependent on the specific pulmonary microcirculatory effects of each drug.

Preauricular skin defects. A consequence of a persistent ectodermal groove.

BACKGROUND: The term aplasia cutis is used to describe congenital localized defects of the skin. This affliction is the end result of various in utero events. Aplasia cutis of the face, although rare, has been associated with numerous dysmorphic features and described under many clinical terms. OBSERVATIONS: We studied 10 patients with oval, atrophic patches distributed in a linear pattern on the preauricular region of the face. Most of the defects were bilateral, and all consistently fell in an oblique line extending from the preauricular region to the angle of the mouth. This line corresponds to the region of fusion between the maxillary and mandibular facial prominences during embryonic development. CONCLUSIONS: This type of facial aplasia cutis may be the result of incomplete fusion of the ectodermal groove between the maxillary and mandibular facial prominences. Although other types of facial skin defects may share a similar pathogenic mechanism, they are distinct in that they occur in different regions and may have other abnormal facial features.