Diffusion magnetic resonance imaging assessment of regional white matter maturation in preterm neonates.

PURPOSE: Diffusion magnetic resonance imaging (dMRI) studies report altered white matter (WM) development in preterm infants. Neurite orientation dispersion and density imaging (NODDI) metrics provide more realistic estimations of neurite architecture in vivo compared with standard diffusion tensor imaging (DTI) metrics. This study investigated microstructural maturation of WM in preterm neonates scanned between 25 and 45 weeks postmenstrual age (PMA) with normal neurodevelopmental outcomes at 2 years using DTI and NODDI metrics. METHODS: Thirty-one neonates (n = 17 male) with median (range) gestational age (GA) 32+1 weeks (24+2-36+4) underwent 3 T brain MRI at median (range) post menstrual age (PMA) 35+2 weeks (25+3-43+1). WM tracts (cingulum, fornix, corticospinal tract (CST), inferior longitudinal fasciculus (ILF), optic radiations) were delineated using constrained spherical deconvolution and probabilistic tractography in MRtrix3. DTI and NODDI metrics were extracted for the whole tract and cross-sections along each tract to assess regional development. RESULTS: PMA at scan positively correlated with fractional anisotropy (FA) in the CST, fornix and optic radiations and neurite density index (NDI) in the cingulum, CST and fornix and negatively correlated with mean diffusivity (MD) in all tracts. A multilinear regression model demonstrated PMA at scan influenced all diffusion measures, GA and GAxPMA at scan influenced FA, MD and NDI and gender affected NDI. Cross-sectional analyses revealed asynchronous WM maturation within and between WM tracts.). CONCLUSION: We describe normal WM maturation in preterm neonates with normal neurodevelopmental outcomes. NODDI can enhance our understanding of WM maturation compared with standard DTI metrics alone.

A Balancing Act: Integrating Evidence-Based Knowledge and Cultural Relevance in a Program of Prevention Parenting Research with Latino/a Immigrants.

Family therapists have a unique opportunity to contribute toward the reduction of widespread mental health disparities impacting diverse populations by developing applied lines of research focused on cultural adaptation. For example, although evidence-based prevention parent training (PT) interventions have been found to be efficacious with various Euro-American populations, there is a pressing need to understand which specific components of PT interventions are perceived by ethnic minority parents as having the highest impact on their parenting practices. Equally important is to examine the perceived cultural relevance of adapted PT interventions. This qualitative investigation had the primary objective of comparing and contrasting the perceived relevance of two culturally adapted versions of the efficacious parenting intervention known as Parent Management Training, the Oregon Model (PMTO). According to feasibility indicators provided by 112 Latino/a immigrant parents, as well as findings from a qualitative thematic analysis, the core parenting components across both adapted interventions were identified by the majority of research participants as relevant to their parenting practices. Participants exposed to the culturally enhanced intervention, which included culture-specific sessions, also reported high satisfaction with components exclusively focused on cultural issues that directly impact their parenting practices (e.g., immigration challenges, biculturalism). This investigation illustrates the relevant contributions that family therapy scholars can offer toward addressing mental health disparities, particularly as it refers to developing community-based prevention interventions that achieve a balance between evidence-based knowledge and cultural relevance.

The effects of hemorrhagic parenchymal infarction on the establishment of sensori-motor structural and functional connectivity in early infancy.

INTRODUCTION: The objective of the study was to characterize alterations of structural and functional connectivity within the developing sensori-motor system in infants with focal perinatal brain injury and at high risk of cerebral palsy. METHODS: Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) data were used to study the developing functional and structural connectivity framework in six infants born prematurely at term equivalent age. This was first characterised in three infants without focal pathology, which was then compared to that derived from three infants with unilateral haemorrhagic parenchymal infarction and a subsequent focal periventricular white matter lesion who developed later haemiparesis. RESULTS: Functional responses to passive hand movement were in the contralateral perirolandic cortex, regardless of focal pathology. In infants with unilateral periventricular injury, afferent thalamo-cortical tracts appeared to have developed compensatory trajectories which circumvented areas of damage. In contrast, efferent corticospinal tracts showed marked asymmetry at term equivalent age following focal brain injury. Sensori-motor network analysis suggested that inter-hemispheric functional connectivity is largely preserved despite pathology and that impairment may be associated with adverse neurodevelopmental outcome. CONCLUSION: Following focal perinatal brain injury, altered structural and functional connectivity is already present and can be characterized with MRI at term equivalent age. The results of this small case series suggest that these techniques may provide valuable new information about prognosis and the pathophysiology underlying cerebral palsy.

The use of a specialised amino acid mixture for pressure ulcers: a placebo-controlled trial.

OBJECTIVE: To compare pressure ulcer healing rates in patients supplemented with a specialised amino acid mixture containing (beta)-hydroxy (beta)-methylbutyrate (HMB), arginine and glutamine, and standard oral nutritional supplements versus patients supplemented with oral nutritional supplements and a placebo mixture. METHOD: Twenty-three inpatients with stage II, III or IV pressure ulcers in an acute care hospital were randomised to recieve (A) a HMB, arginine and glutamine mixture twice daily alongside oral nutritional supplements (n=11) or (B) standard nutritional care alongside oral nutritional supplements (n=12) for 2 weeks. Pressure ulcers were measured weekly for area, depth and Pressure Ulcer Scale for Healing (PUSH) scores. The proportion of viable tissue was determined based on area of wound tracing. Weekly laboratory tests were performed to measure C-reactive protein and pre-albumin levels. This trial is registered at http://ClinicalTrials.gov under NCT01090076. RESULTS: There was no difference between anthropometrical measurements, biochemical parameters and nutritional intake pre- and post- study. Wound area did not decrease significantly in the short term for both groups. The proportion of viable tissues increased within 2 weeks on HMB, arginine and glutamine supplementation (p=0.02). PUSH scores showed significant improvement within 1 week of supplementation for the experimental group (p=0.013). CONCLUSION: The use of specialised amino acid does not appear to reduce wound size and PUSH scores but may improve tissue viability after 2 weeks. Further confirmation on a larger scale is required to determine the benefits of supplementing additional HMB, arginine and glutamine in patients with pressure ulcers.

Evidence for gene transfer and expression of factor IX in haemophilia B patients treated with an AAV vector.

Pre-clinical studies in mice and haemophilic dogs have shown that introduction of an adeno-associated viral (AAV) vector encoding blood coagulation factor IX (FIX) into skeletal muscle results in sustained expression of F.IX at levels sufficient to correct the haemophilic phenotype. On the basis of these data and additional pre-clinical studies demonstrating an absence of vector-related toxicity, we initiated a clinical study of intramuscular injection of an AAV vector expressing human F.IX in adults with severe haemophilia B. The study has a dose-escalation design, and all patients have now been enrolled in the initial dose cohort (2 x 10(11) vg/kg). Assessment in the first three patients of safety and gene transfer and expression show no evidence of germline transmission of vector sequences or formation of inhibitory antibodies against F.IX. We found that the vector sequences are present in muscle by PCR and Southern-blot analyses of muscle biopsies and we demonstrated expression of F.IX by immunohistochemistry. We observed modest changes in clinical endpoints including circulating levels of F.IX and frequency of FIX protein infusion. The evidence of gene expression at low doses of vector suggests that dose calculations based on animal data may have overestimated the amount of vector required to achieve therapeutic levels in humans, and that the approach offers the possibility of converting severe haemophilia B to a milder form of the disease.

A common neonatal image phenotype predicts adverse neurodevelopmental outcome in children born preterm.

Diffuse white matter injury is common in preterm infants and is a candidate substrate for later cognitive impairment. This injury pattern is associated with morphological changes in deep grey nuclei, the localization of which is uncertain. We test the hypotheses that diffuse white matter injury is associated with discrete focal tissue loss, and that this image phenotype is associated with impairment at 2years. We acquired magnetic resonance images from 80 preterm infants at term equivalent (mean gestational age 29(+6)weeks) and 20 control infants (mean GA 39(+2)weeks). Diffuse white matter injury was defined by abnormal apparent diffusion coefficient values in one or more white matter region (frontal, central or posterior white matter at the level of the centrum semiovale), and morphological difference between groups was calculated from 3D images using deformation based morphometry. Neurodevelopmental assessments were obtained from preterm infants at a mean chronological age of 27.5months, and from controls at a mean age of 31.1months. We identified a common image phenotype in 66 of 80 preterm infants at term equivalent comprising: diffuse white matter injury; and tissue volume reduction in the dorsomedial nucleus of the thalamus, the globus pallidus, periventricular white matter, the corona radiata and within the central region of the centrum semiovale (t=4.42 p<0.001 false discovery rate corrected). The abnormal image phenotype is associated with reduced median developmental quotient (DQ) at 2years (DQ=92) compared with control infants (DQ=112), p<0.001. These findings indicate that specific neural systems are susceptible to maldevelopment after preterm birth, and suggest that neonatal image phenotype may serve as a useful biomarker for studying mechanisms of injury and the effect of putative therapeutic interventions.

Specificities and V genes encoding monoclonal autoantibodies from viable motheaten mice.

Several hundred hybridomas were obtained from 1-2-mo-old viable motheaten (mev) mice. Among the Ig-secreting hybridomas tested, greater than 50% (17/33) exhibited reactivity for autoantigens, supporting the idea that the Ly-1 B cells that predominate in mev mice contain frequent precursors of autoantibody-forming cells. Certain of the specificities of these autoantibodies correlated with the documented pathophysiology of mev mice (antithymocyte, -erythrocyte, -skin, -kidney, and -IgG); others were specific for autoantigens not previously observed in motheaten mice but though to be involved in other autoimmune diseases (e.g., intrinsic factor, transferrin, myelin basic protein, and thyroglobulin). About 2 of 3 (11/17) of the self-reactive antibodies exhibited multispecific binding activity for various autoantigens. Analysis by Northern blotting of the V gene families used in mev autoantibodies showed a random usage of VH families and a biased usage of four Vk gene families. Of 16 autoantibodies tested, 12 used a Vk gene from the Vk1, 4, 10, or 19 families. These patterns of Vk gene usage differ from nonautoimmune control animals. Overall, an immunoregulatory defect operating at a more generalized level than the VH or Vk loci, and due to a single gene mutation, appears to be responsible for the multiple immune abnormalities of mev mice.

Frontal fibrosing alopecia: a clinical review of 36 patients.

BACKGROUND: Frontal fibrosing alopecia (FFA) is a primary lymphocytic cicatricial alopecia with a distinctive clinical pattern of progressive frontotemporal hairline recession. Currently, there are no evidence-based studies to guide treatment for patients with FFA; thus, treatment options vary among clinicians. OBJECTIVES: We report clinical findings and treatment outcomes of 36 patients with FFA, the largest cohort to date. Further, we report the first evidence-based study of the efficacy of hydroxychloroquine in FFA using a quantitative clinical score, the Lichen Planopilaris Activity Index (LPPAI). METHODS: A retrospective case note review was performed of 36 adult patients with FFA. Data were collected on demographics and clinical findings. Treatment responses to hydroxychloroquine, doxycycline and mycophenolate mofetil were assessed using the LPPAI. Adverse events were monitored. RESULTS: Most patients in our cohort were female (97%), white (92%) and postmenopausal (83%). Apart from hairline recession, 75% also reported eyebrow loss. Scalp pruritus (67%) and perifollicular erythema (86%) were the most common presenting symptom and sign, respectively. A statistically significant reduction in signs and symptoms in subjects treated with hydroxychloroquine (P < 0·05) was found at both 6- and 12-month follow up. CONCLUSIONS: In FFA, hairline recession, scalp pruritus, perifollicular erythema and eyebrow loss are common at presentation. Despite the limitations of a retrospective review, our data reveal that hydroxychloroquine is significantly effective in reducing signs and symptoms of FFA after both 6 and 12 months of treatment. However, the lack of a significant reduction in signs and symptoms between 6 and 12 months indicates that the maximal benefits of hydroxychloroquine are evident within the first 6 months of use.

MRI Findings at Term-Corrected Age and Neurodevelopmental Outcomes in a Large Cohort of Very Preterm Infants.

BACKGROUND AND PURPOSE: Brain MR imaging at term-equivalent age is a useful tool to define brain injury in preterm infants. We report pragmatic clinical radiological assessment of images from a large unselected cohort of preterm infants imaged at term and document the spectrum and frequency of acquired brain lesions and their relation to outcomes at 20 months. MATERIALS AND METHODS: Infants born at <33 weeks' gestation were recruited from South and North West London neonatal units and imaged in a single center at 3T at term-equivalent age. At 20 months' corrected age, they were invited for neurodevelopmental assessment. The frequency of acquired brain lesions and the sensitivity, specificity, and negative and positive predictive values for motor, cognitive, and language outcomes were calculated, and corpus callosal thinning and ventricular dilation were qualitatively assessed. RESULTS: Five hundred four infants underwent 3T MR imaging at term-equivalent age; 477 attended for assessment. Seventy-six percent of infants had acquired lesions, which included periventricular leukomalacia, hemorrhagic parenchymal infarction, germinal matrix-intraventricular hemorrhage, punctate white matter lesions, cerebellar hemorrhage, and subependymal cysts. All infants with periventricular leukomalacia, and 60% of those with hemorrhagic parenchymal infarction had abnormal motor outcomes. Routine 3T MR imaging of the brain at term-equivalent age in an unselected preterm population that demonstrates no focal lesion is 45% sensitive and 61% specific for normal neurodevelopment at 20 months and 17% sensitive and 94% specific for a normal motor outcome. CONCLUSIONS: Acquired brain lesions are common in preterm infants routinely imaged at term-equivalent age, but not all predict an adverse neurodevelopmental outcome.

Haplotype variation and linkage disequilibrium in 313 human genes.

Variation within genes has important implications for all biological traits. We identified 3899 single nucleotide polymorphisms (SNPs) that were present within 313 genes from 82 unrelated individuals of diverse ancestry, and we organized the SNPs into 4304 different haplotypes. Each gene had several variable SNPs and haplotypes that were present in all populations, as well as a number that were population-specific. Pairs of SNPs exhibited variability in the degree of linkage disequilibrium that was a function of their location within a gene, distance from each other, population distribution, and population frequency. Haplotypes generally had more information content (heterozygosity) than did individual SNPs. Our analysis of the pattern of variation strongly supports the recent expansion of the human population.

Worry about Performance: Unravelling the Relationship between 'Doing More' and 'Doing Better'.

OBJECTIVE: Recent studies have described worry about caregiver performance (WaP) as a distinct dimension of caregiver burden. We aimed to explore care recipient and caregiver characteristics between the concordant and discordant WaP groups in a population of caregivers of older adults with cognitive impairment. The secondary objective is to explore if there are differences between high and low WaP subsets in the 'doing more' and 'doing better' groups. DESIGN, SETTING AND PARTICIPANTS: This is a retrospective study of 936 dyads of community-dwelling older adults with cognitive complaints and their primary family caregiver from a hospital in Singapore. MEASUREMENTS: We performed descriptive and inferential statistics of the characteristics of caregivers and patients. We categorized caregiver-patient dyads into four groups, namely concordant (high vs low WaP) and discordant ('doing more' vs 'doing better') groups. For both concordant and discordant groups, we further defined low and high WaP subgroups using tertile cutoffs. RESULTS: The concordant low WaP group is predicted by the spousal relationship (p<.001) and care recipients with fewer neuropsychiatric symptoms (p<.001). There is no significant difference between the discordant groups, which were predominantly the adult children. Further analysis of subgroups found that in the 'doing better' group, there were more spouses in the high as compared to low WaP subgroups, with the reverse true in the 'doing more' group. In the 'doing more' group, caregivers with high WaP also had higher total ZBI (p<0.05) with higher factors (F1, F2 and F3) scores (p<0.05). They also endorsed higher NPI-Q scores (p=0.045) particularly in the domain of depression / dysphoria (p=0.034). These differences are not seen in the 'doing better' group. CONCLUSION: Our study suggests an association with caregiver characteristics (adult child) and disruptive behavior in the 'do more' high WaP discordant group. Delineating into the high and low WaP subgroups can help us identify the 'do more' high WaP subgroup that merits further attention and early intervention.

Frontal Assessment Battery in Early Cognitive Impairment: Psychometric Property and Factor Structure.

BACKGROUND: The Frontal Assessment Battery (FAB) is a reliable and valid bedside tool for testing executive function in dementia. Given the increasing interest in utility of FAB as a screening tool in early cognitive impairment (ECI), there is a surprising lack of studies evaluating its psychometric property and factor structure, nor the influence of factors such as age, education and gender, in ECI. OBJECTIVES: This study aims to investigate the psychometric properties and factor structure of FAB in older adults with ECI, as well as the influence of age, gender and education. DESIGN, SETTING AND PARTICIPANTS: This is a retrospective, observational cross-sectional study with 300 community dwelling, predominantly Chinese older adults (14 normal, 130 mild cognitive impairment (MCI), and 156 mild dementia) who presented to Memory Clinic from January 2011 to December 2013. Measurements and Analysis: We collected data on demographic, cognitive, functional and behavioral evaluation. To examine the psychometric properties of FAB, we examined the concurrent, convergent, and discriminant validity; internal consistency by Cronbach's alpha; and factor structure by exploratory factor analysis. The influence of age, education and gender was examined using unadjusted and adjusted correlational analyses with CDR-SOB. We performed analysis for the whole group and for MCI subgroup. RESULTS: FAB total score decreases significantly from normal to dementia group attesting to concurrent validity. It correlated significantly with digit span backwards and Chinese Mini Mental State Examination (r=0.38 and 0.47 respectively, p<0.01) and poorly with Neuropsychiatric Inventory-Questionnaire and depression (r=0.004 and -0.02 respectively), supporting its convergent and discriminant validity. Factor analysis yielded a single-factor solution for FAB with fair Internal consistency (alpha=0.610). FAB is relatively unaffected by age, gender and education level. These good psychometric properties extend to MCI, albeit with greater influence by education level. FAB items of conceptualization and mental flexibility have good discriminatory ability between MCI and normal subjects. CONCLUSION: FAB has good concurrent, convergent and discriminant validity with fair internal consistency in ECI that is premised on a one-factor structure. It is relatively unaffected by age, gender or education. Taken together, FAB is a useful bedside screening tool for executive function in ECI.

Effects of allergen on airway narrowing dynamics as assessed by lung-slice technique.

Asthma is characterised by an excessive airway narrowing in response to a variety of stimuli, called airway hyperresponsiveness (AHR). Previous comparisons between mouse strains have shown that increased velocity of airway narrowing correlates with baseline airway responsiveness. These data prompted the investigation into models of induced AHR to see whether airway narrowing dynamics correlated with in vivo responsiveness. In an attempt to reproduce some of the features of asthma, BALB/c mice were sensitised and subjected to either brief or chronic periods of allergen exposure. Brief exposure involved two challenges with intranasal chicken egg ovalbumin (OVA(in)). Chronic exposure involved six 2-day periods of OVA(in) challenges, each separated by 12 days. Control mice received intranasal saline challenges. Outcomes included videomicrometry of lung slices (magnitude and velocity of airway narrowing), in vivo respiratory physiology measurements and histological staining with morphometric analysis. Neither brief nor chronic allergen exposure resulted in greater airway narrowing and increased velocity compared with saline controls. Structural changes in the airway, such as goblet cell hyperplasia, subepithelial fibrosis and increased contractile tissue, were detected in mice chronically challenged with allergen. In conclusion, increased responsiveness to methacholine following allergen challenge may not be due to an intrinsic change to the smooth muscle per se, but rather to other changes in the lung, which ultimately manifest as an increase in respiratory resistance.

Altered white matter and cortical structure in neonates with antenatally diagnosed isolated ventriculomegaly.

Ventriculomegaly (VM) is the most common central nervous system abnormality diagnosed antenatally, and is associated with developmental delay in childhood. We tested the hypothesis that antenatally diagnosed isolated VM represents a biological marker for altered white matter (WM) and cortical grey matter (GM) development in neonates. 25 controls and 21 neonates with antenatally diagnosed isolated VM had magnetic resonance imaging at 41.97(± 2.94) and 45.34(± 2.14) weeks respectively. T2-weighted scans were segmented for volumetric analyses of the lateral ventricles, WM and cortical GM. Diffusion tensor imaging (DTI) measures were assessed using voxel-wise methods in WM and cortical GM; comparisons were made between cohorts. Ventricular and cortical GM volumes were increased, and WM relative volume was reduced in the VM group. Regional decreases in fractional anisotropy (FA) and increases in mean diffusivity (MD) were demonstrated in WM of the VM group compared to controls. No differences in cortical DTI metrics were observed. At 2 years, neurodevelopmental delays, especially in language, were observed in 6/12 cases in the VM cohort. WM alterations in isolated VM cases may be consistent with abnormal development of WM tracts involved in language and cognition. Alterations in WM FA and MD may represent neural correlates for later neurodevelopmental deficits.

Thoracoscopic and laparoscopic esophagectomy: initial experience and outcomes.

BACKGROUND: Although surgical resection currently is the preferred treatment for fit patients with resectable esophageal cancers, it is associated with a relatively high risk of morbidity and significant perioperative mortality. Currently, a range of open surgical approaches are used. More recently, minimally invasive approaches have become feasible, with the potential to reduce perioperative morbidity. This study investigated the outcomes from one such approach. METHODS: Outcome data were collected prospectively for 36 consecutive patients who underwent a minimally invasive esophagectomy for esophageal cancer. A three-stage approach was used, with all the patients undergoing a thoracoscopic esophageal mobilization, combined with either open or hand-assisted laparoscopic abdominal gastric mobilization, and open cervical anastomosis. An open abdominal approach was used for 15 of the patients and a hand-assisted laparoscopic approach for 21. A total of 34 patients had invasive malignancy, whereas 2 had preinvasive disease. A group of 23 patients (68%) who had invasive malignancies also received neoadjuvant chemotherapy and radiotherapy. RESULTS: The mean operating time ranged from 190 to 360 min (mean, 263 min). The median postoperative hospital stay was 16 days. In-hospital mortality was 5.5% (2/36), and perioperative morbidity was 41%. The perioperative outcomes for patients undergoing an open abdominal approach and those who had hand-assisted laparoscopic surgery were similar. For the patients who underwent a hand-assisted laparoscopic abdominal procedure, the total operating time was shorter (248 vs 281 min), and the blood loss was less (223 vs 440 ml). The median follow-up period was 30 months. The 4-year survival predicted by Kaplan-Meir for the 34 patients with invasive malignancy was 44%. CONCLUSION: The outcome for esophagectomy using thoracoscopic esophageal mobilization, with or without hand-assisted laparoscopic abdominal surgery, was comparable with data from conventional open surgical approaches. These approaches can be performed with an acceptable level of perioperative morbidity. Further application of these techniques, with close scrutiny of outcome data, is appropriate.

Cutaneous bioassay of salicylic acid as a keratolytic.

Keratolytic efficacy of topical preparations containing salicylic acid was studied in humans utilizing adhesive tape stripping and quantifying SC removal by protein analysis. In combination with tape stripping, squamometry was used to evaluate the influence of salicylic acid on skin surface scaliness and desquamation. Furthermore, skin barrier perturbation and skin irritancy was recorded and related to the dermatopharmacological effect of the preparations. In contrast to squamometry, tape stripping combined with protein analysis was sensitive in detecting keratolytic effect of salicylic acid within hours of application. Importantly, whereas the pH of the preparations only minimally influenced efficacy, local dermatotoxicity was significantly increased at acidic pH. This indicates that the quest to increase the amount of free, non-dissociated SA is, in fact, counterproductive as the more acidic preparations resulted in skin irritation and barrier disruption.

Dermatology--24th Hawaii Seminar. 7-12 February 2000, Big Island, HI, USA.

At this seminar, several encouraging developments were demonstrated in various areas of dermatology practice. Much attention was focused on topical tacrolimus, the US approval of which, for the treatment of atopic dermatitis is much anticipated. The general consensus from trials was that the drug is safe and effective, and it is hoped that it will be of use in pediatric cases. Additional data were presented regarding the use of cyclosporin in psoriasis patients, with some evidence that low doses could be delivered safely with adequate monitoring. Safety was an issue in many of the sessions, reflecting the increasing involvement of potentially toxic therapies within dermatology. The debate regarding the use of topical tretinoin during pregnancy continues, and pharmacokinetic evidence was presented to demonstrate that systemic absorption of the drug is minimal. The range of diseases treated by topical imiquimod may be expanded with data suggesting that it may have benefits in the treatment of basal cell carcinomas. Surgical dermatology also featured heavily in the meeting, reflecting the more interventional approaches favored by dermatologists today.

Multiple corticosteroid orally elicited allergic contact dermatitis in a patient with multiple topical corticosteroid allergic contact dermatitis.

Corticoid allergic contact dermatitis (ACD) may be topically or systemically elicited. Allergic contact dermatitis to topical corticosteroids is relatively common, whereas reports of orally elicited ACD to corticosteroids are rarer. Patients allergic to one corticosteroid often exhibit cross-reactivity to other corticoids. We have previously reported a 46-year-old woman with contact allergy documented by patch and provocative use testing to multiple topical corticosteroids. On further testing, she was thought to have multiple corticoid orally elicited ACD to triamcinolone, methyl prednisolone, dexamethasone, and prednisone. Oral provocation tests were performed in a single-blind fashion following the method of Alanko and Kauppinen [Diagnosis of drug eruptions: clinical evaluation and drug challenges. In, Skin Reactions to Drugs (Kauppinen K, Alanko K, Hannuksela M, Maibach HI, eds). Boca Raton, FL, CRC Press, 1998.]. The five oral corticosteroids tested were triamcinolone, methyl prednisolone, dexamethasone, prednisone, and hydrocortisone. Four of the five challenged corticosteroids (i.e., triamcinolone, methyl prednisolone, dexamethasone, and prednisone) produced a generalized maculopapular eruption in a delayed manner. The fifth challenged corticoid, hydrocortisone, had no adverse effect on this patient. This patient was unusual in that she exhibited polysensitivity to a spectrum of oral and topical corticosteroids. Hydrocortisone was identified as a corticosteroid for future clinical use. This is an important finding since corticosteroids are important emergency drugs.

Medicolegal aspects of breast cancer in U.S. federal medical facilities: analysis of 80 claims.

Eighty malpractice claims were taken against the U.S. government alleging negligence and delay in the diagnosis of breast cancer in federal medical facilities during the period from 1980 to 1989. Medical records and claim documents were reviewed together with the opinions of expert witnesses, journal articles, and opinions of the Department of Legal Medicine of the Armed Forces Institute of Pathology. The radiology and pathology reports were reviewed. Of the 80 claims, 68 were closed; compensation amounts ranged from $6,000 to $1 million. There was no correlation between the length of delay in diagnosis and the amount of compensation paid. The reasons for delayed diagnosis are considered in detail, and recommendations are made in an attempt to minimize the number of such claims in the future.