Solitary fibrous tumor of the orbit in a 1-year-old patient: a case report.

Solitary fibrous tumors (SFTs) are rare neoplasms of mesenchymal origin. While the mean age of presentation is 58 years old, we report the case of the youngest documented patient with an SFT of the orbit. A 13-month-old child was evaluated for eyelid asymmetry and then referred to the oculoplastic service. On examination, a soft tissue mass of the right inferomedial orbit was observed. MRI demonstrated a well-circumscribed, extraocular lesion in the inferomedial right orbit, potentially fibrous in nature. Excision was performed without complications. Pathologic examination demonstrated fibrous tissue proliferation with a staghorn vascular pattern, as well as benign fibrous cells with tapering nuclei and abundant pericellular reticulin. Immunohistochemistry (IHC) demonstrated that the cells stain diffusely positive for CD34 and vimentin. With the MRI findings, pathology, and IHC, the diagnosis was confirmed to be SFT. SFTs of the orbit, although rare, may occur in the pediatric population.

Factors Influencing Longitudinal Stair Climb Performance from Midlife to Early Late Life: The Study of Women's Health Across the Nation Chicago and Michigan Sites.

OBJECTIVES: To quantify the longitudinal change in stair climb performance (a measure indicative of both physical function and muscle power), determine whether physical activity is related to slower decline in performance, and to identify factors that modify the longitudinal change in performance among women from midlife to late life. DESIGN: Longitudinal cohort study with up to 15 study visits. SETTING: Two sites of the Study of Women's Health Across the Nation. PARTICIPANTS: Black (n=411) and white (N=419) women followed from median age 47.0 (44.6-49.6) to 62.0 (55.8-65.3) years. INTERVENTIONS: N/A. MEASUREMENTS: Performance on a stair climb test (ascend/descend 4 steps, 3 cycles) was timed. Physical activity (PA) was assessed using the Kaiser Physical Activity Survey (KPAS; possible range 0-15 points). Sociodemographic and health factors were assessed via self-report. BMI was calculated with measured height and weight. Mixed-effects regression modeled longitudinal change in stair climb performance. RESULTS: Average baseline stair climb time was 18.12 seconds (95% CI: 17.83-18.41), with 0.98% (95% CI: 0.84%-1.11%) annual slowing. In fully adjusted models, higher levels of PA were associated with faster stair climb times (2.09% faster per point higher, 95% CI: -2.87%- -1.30%), and black women had 5.22% (95% CI: 2.43%-8.01%) slower performance compared to white women. Smoking, financial strain, diabetes, osteoarthritis, fair/poor health, and stroke were associated with 3.36% (95% CI: 0.07%-6.65%), 7.56% (95% CI: 4.75%-10.37%), 8.40% (95% CI: 2.89%-13.92%), 8.46% (95% CI: 5.12%-11.79%), 9.16% (95% CI: 4.72%-13.60%), and 16.94% (95% CI: 5.37%-28.51%) slower performance, respectively. In separate models, higher BMI (per 1-unit), osteoarthritis, fair/poor health, and diabetes, were each associated with 0.06% (95% CI:0.04%-0.08%), 0.48% (95% CI:0.12%-0.84%), 0.81% (95% CI:0.35%-1.28%), and 0.84% (95% CI:0.22%-1.46%), additional slowing per year over time. CONCLUSION: Significant declines in function were evident as women transitioned from midlife to early late life. Declines were amplified by indicators of poor health, emphasizing the importance of health in midlife for promoting healthy aging.

Exome sequencing in 32 patients with anophthalmia/microphthalmia and developmental eye defects.

Anophthalmia/microphthalmia (A/M) is a genetically heterogeneous birth defect for which the etiology is unknown in more than 50% of patients. We used exome sequencing with the ACE Exome(TM) (Personalis, Inc; 18 cases) and UCSF Genomics Core (21 cases) to sequence 28 patients with A/M and four patients with varied developmental eye defects. In the 28 patients with A/M, we identified de novo mutations in three patients (OTX2, p.(Gln91His), RARB, p.Arg387Cys and GDF6, p.Ala249Glu) and inherited mutations in STRA6 in two patients. In patients with developmental eye defects, a female with cataracts and cardiomyopathy had a de novo COL4A1 mutation, p.(Gly773Arg), expanding the phenotype associated with COL4A1 to include cardiomyopathy. A male with a chorioretinal defect, microcephaly, seizures and sensorineural deafness had two PNPT1 mutations, p.(Ala507Ser) and c.401-1G>A, and we describe eye defects associated with this gene for the first time. Exome sequencing was efficient for identifying mutations in pathogenic genes for which there is no clinical testing available and for identifying cases that expand phenotypic spectra, such as the PNPT1 and COL4A1-associated disorders described here.

The Long and Short of Genetic Counseling Summary Letters: A Case-control Study.

Genetic counseling summary letters are intended to reinforce information received during genetic counseling, but little information is available on patient/family responses to these letters. We conducted a case-control study to assess the effectiveness of two different letter formats. Parents of children receiving a new diagnosis were enrolled. The control group (n = 85) received a genetic counseling summary letter in a narrative format, 4-5 pages in length. After the control enrollment period, genetic counselors were trained by a professional medical writer to develop a concise letter format. The case group (n = 64) received a concise letter, approximately 1.5 pages in length, utilizing simple sentences, lay terms, and lists/bullet points. Parents completed a survey 4 weeks after the visit to rate the letter's format, usefulness, and their emotional reaction. Results show that parents in the case group rated the letter more highly (p = 0.023), particularly in the emotional response dimension (rating changes in anxiety, depression, fear, ability to cope, and confidence in response to the letter). Parents in the case group also rated the genetic counseling session more highly (p = 0.039). In the control group, parents without a college degree were more likely to rate the letter as too long and the level of medical detail as too high. In the case group, no significant differences were seen between parents with or without a college degree. These data suggest that a short genetic counseling summary letter is rated higher by parents, and is particularly associated with a more positive emotional reaction. A short letter format highlighting the basic facts related to the genetic condition may be more useful to parents of diverse educational backgrounds, and may support a positive emotional adaptation at the time of a new diagnosis. Genetic counselors may benefit from specific instruction in medical and educational writing.

FAM20A mutations associated with enamel renal syndrome.

We identified two families with an autosomal-recessive disorder manifested by severe enamel hypoplasia, delayed and failed tooth eruption, misshapen teeth, intrapulpal calcifications, and localized gingival hyperplasia. Genetic analyses identified novel FAM20A mutations associated with the disease phenotype in both families. The proband of Family 1 had an altered splice junction in Intron 1 (g.502011G>C; c.405-1G>C) and a missense mutation in Exon 8 (g.65094G>A; c.1207G>A; p.D403N). The missense mutation is notable because D(403) is strictly conserved among FAM20A homologues, and the corresponding defect in FAM20C caused osteosclerotic bone dysplasia and a loss of kinase activity. The proband at age 12 yrs tested negative for nephrocalcinosis. The proband and her affected father in Family 2 were homozygous for a single nucleotide deletion that altered a splice junction in Intron 10 (g.66622del; c.1361+4del). Minigene analyses demonstrated that this alteration precluded normal splicing. Immunohistochemistry (IHC) of mouse maxillary first molars localized FAM20A in secretory-stage ameloblasts, in odontoblasts, and in the eruption pathway. IHC of kidneys localized FAM20A in the renal tubules. We conclude that FAM20A is likely a secretory pathway kinase and that loss-of-function mutations cause pathology where its phosphorylations are necessary for normal development or homeostasis.

Diagnostic exome sequencing identifies two novel IQSEC2 mutations associated with X-linked intellectual disability with seizures: implications for genetic counseling and clinical diagnosis.

Intellectual disability is a heterogeneous disorder with a wide phenotypic spectrum. Over 1,700 OMIM genes have been associated with this condition, many of which reside on the X-chromosome. The IQSEC2 gene is located on chromosome Xp11.22 and is known to play a significant role in the maintenance and homeostasis of the brain. Mutations in IQSEC2 have been historically associated with nonsyndromic X-linked intellectual disability. Case reports of affected probands show phenotypic overlap with conditions associated with pathogenic MECP2, FOXG1, CDKL5, and MEF2C gene mutations. Affected individuals, however, have also been identified as presenting with additional clinical features including seizures, autistic-behavior, psychiatric problems, and delayed language skills. To our knowledge, only 5 deleterious mutations and 2 intragenic duplications have been previously reported in IQSEC2. Here we report two novel IQSEC2 de novo truncating mutations identified through diagnostic exome sequencing in two severely affected unrelated male probands manifesting developmental delay, seizures, hypotonia, plagiocephaly, and abnormal MRI findings. Overall, diagnostic exome sequencing established a molecular diagnosis for two patients in whom traditional testing methods were uninformative while expanding on the mutational and phenotypic spectrum. In addition, our data suggests that IQSEC2 may be more common than previously appreciated, accounting for approximately 9 % (2/22) of positive findings among patients with seizures referred for diagnostic exome sequencing. Further, these data supports recently published data suggesting that IQSEC2 plays a more significant role in the development of X-linked intellectual disability with seizures than previously anticipated.

Designing intervention effectiveness studies for occupational health and safety: The Minnesota Wood Dust Study.

BACKGROUND: A planning model was used to guide the design of a randomized controlled study of the effectiveness of tailored interventions in lowering dust exposures in small woodworking shops. METHODS: Guided by Green's PRECEDE-PROCEED model, we used a planning committee, focus groups and a pilot study to gain information on small woodworking shops, causes of and controls for high dust levels, and barriers and incentives surrounding availability and use of dust controls. RESULTS: The planning committee identified key characteristics of small woodworking shop owners. Focus groups with owners and employees served to further elucidate why dust control was considered unimportant. The pilot study gave measures of dust exposures, tasks, and use of controls. Interventions focused on providing owners with technical and economic assistance to lower dust levels and an educational program for employees discussing health effects and effective methods of dust control. CONCLUSIONS: The PRECEDE-PROCEED model proved a useful framework for designing an intervention in the occupational setting.

A putative beta2-adrenoceptor from the rainbow trout (Oncorhynuchus mykiss). Molecular characterization and pharmacology.

Extensive molecular characterization of mammalian beta-adrenoceptors has revealed complex modes of regulation and interaction. Relatively little attention, however, has focused on adrenoceptors from early branching vertebrates such as fish. Using an RT-PCR approach we have cloned a rainbow trout beta2-adrenoceptor gene that codes for a 409-amino-acid protein with the same seven transmembrane domain structure as its mammalian counterparts. This rainbow trout beta2-adrenoceptor shares a high degree of amino-acid sequence conservation with other vertebrate beta2-adrenoceptors. The conclusion that this sequence is a rainbow trout beta2-adrenoceptor is further supported by phylogenetic analysis of vertebrate beta-adrenoceptor sequences and competitive pharmacological binding data. RNase protection assays demonstrate that the rainbow trout beta2-adrenoceptor gene is highly expressed in the liver and red and white muscle, with lower levels of expression in the gills, heart, kidney and spleen of the rainbow trout. The lack of regulatory phosphorylation sites within the G-protein-binding domain of the rainbow trout beta2-adrenoceptor sequence suggests that the in vivo control of trout beta2-adrenoceptor signaling differs substantially from that of mammals.

Phacofragmentation for morgagnian cataract in a horse.

A 3-year-old Paint gelding was presented for sudden onset of cataract affecting the right eye. Ophthalmic examination revealed subtle to mild microphthalmia and a mature cataract affecting the right globe. The right eye was treated with an antibiotic-corticosteroid ophthalmic ointment and phacofragmentation was recommended. On re-examination 5 months later, resorption of the cortex of the right lens and a morgagnian cataract were evident. The nucleus was positioned ventronasally in the lens capsule. The right eye had light perception, and a menace response was present. Examination of the right fundus via binocular indirect ophthalmoscopy was not possible. Ophthalmic ultrasonography revealed that the right globe was 4 mm shorter in axial length when compared with the left globe. There was a marked reduction in the size of the right lens vs. the left lens, and the presence of a moderate amount of hyperechoic debris was identified within the vitreal compartment of the right globe. Phacofragmentation, irrigation and aspiration of the morgagnian cataract and an anterior vitrectomy were performed. On postoperative examination, the eye was comfortable and a menace response was present. The horse regained useful vision and continues to have a comfortable, visual eye 7 months postoperatively.

Inhalable dust exposures, tasks, and use of ventilation in small woodworking shops: a pilot study.

Measures of workers' inhalable dust exposures, tasks, and ventilation use were made in five small woodworking shops prior to the start of an intervention effectiveness study aimed at lowering personal wood dust exposures. The data were used to (1) design a sampling protocol for an intervention success measure, (2) identify targets for intervention among the tasks and activities responsible for high dust levels, and (3) develop shop-level measures as tools for tailoring intervention activities. Geometric mean dust concentrations ranged from 1.6 to 9.9 mg/m3 in the five shops, with the highest levels occurring in a cabinet shop. All shops had centralized dust collection systems and workers generally used dust control on stationary tools (60-100% of the time) when it was available. Sanding with both stationary and handheld powered tools, cleaning with methods that can disperse dust (e.g., brushes, compressed air), and miscellaneous tasks were all responsible for significant personal exposures. The positive association between miscellaneous tasks and exposures probably reflects the high background levels generated by nearby processes. Sanding with both stationary tools and handheld powered tools represents the most significant influence on personal exposures in small woodworking shops. The authors conclude that pilot studies are useful tools for designing occupational health and safety intervention effectiveness studies.

Use of canaliculorhinostomy for repair of nasolacrimal duct obstruction in a horse.

Obstruction of the nasolacrimal outflow pathway in horses is not uncommon. Causes of obstruction include foreign bodies, trauma, and congenital abnormalities. Placement of a nasolacrimal retention stylette may prove challenging.

Structure of interfacial liquids: X-ray scattering studies.

We have used synchrotron x rays to study three different liquids near solid-liquid interfaces. For either ultrathin (45-90 A) or thick ( approximately 5000 A) liquid films on silicon substrates, we find (on the basis of diffraction peaks or specular reflectivity data) that the molecules form 3-6 layers at the interface, with plane spacings close to the molecular dimensions. Rough surfaces and/or impurities reduce the density oscillation amplitudes. Making the liquid film very thin does not observably enhance the effect, which implies that layering is present even at an isolated interface (i.e., in a semi-infinite liquid). On the other hand, predeposited impurities diffuse away from the interface more easily if the liquid films are thick. The liquids studied are nonconducting, nonpolar, and nonreactive; the molecules are roughly spherical; and our substrate surface has no lateral structure. Thus our observations should apply to any liquid near a hard wall.

Muscle fatigue and muscle injury.

The purpose of this review is to acquaint the reader with the neurobiology of muscle fatigue. Muscle fatigue is a complex, multifactorial process. The authors have covered the chain of events bringing about skeletal muscle contraction and the manner in which fatigue may affect each step. Advances in technology continue to increase understanding of central fatigue. Many excellent studies of peripheral fatigue have been designed to delineate the mechanisms that influence the excitation-contraction coupling, energy supply, and force generation processes. Although much of this work has considered mechanisms in isolation, different mechanisms may be responsible under different conditions. Fatigue is a common complaint among patients with a variety of neuromuscular and metabolic diseases. Armed with an enhanced knowledge of the mechanisms of muscle fatigue, one can more fully recognize the signs and symptoms of metabolic disorders and neuromuscular diseases and use diagnostic testing. The clinician should anticipate the role of muscle fatigue in injury and focus on injury prevention strategies, especially during the restorative phase of rehabilitation. As a clinician-scientist concerned with optimizing patients' and athletes' performance, one must design ways to identify, measure, and treat muscle fatigue. Beyond illustrating what is currently known about muscle fatigue, the authors hope this review inspires the reader to solve problems of great clinical importance to patients and athletes alike.

A retrospective review of the incidence and rehabilitation outcome of concomitant traumatic brain injury and ligamentous knee injury.

OBJECTIVES: To estimate the incidence of ligamentous knee injuries in patients with traumatic brain injury (TBI) involved in pedestrian versus motor vehicle collisions (PVMVC), to identify associated risk factors, and to compare rehabilitation outcomes and costs in TBI patients with and without ligamentous knee injury. DESIGN: Retrospective, case control. SETTING: An academic rehabilitation hospital with a large metropolitan referral base. PATIENTS: Twenty-three consecutive adolescent and adult subjects admitted for acute inpatient rehabilitation after a PVMVC from January 1, 1994, to January 1, 1996. RESULTS: Five subjects (22%) were found to have a ligamentous knee injury, one with bilateral injuries. Two of these six injuries were diagnosed only after presentation to the rehabilitation setting. The most common injury was an anterior cruciate ligament (ACL) disruption in 5 of 6 knees. A coupled ACL and medial collateral ligament injury was identified in 4 of 6 injured knees. The risk of ligamentous knee injury was most closely associated with the presence of a tibial plateau fracture (n=3) (chi2=12.420, p < .001). There was no statistical difference between groups with and without ligamentous knee injuries with respect to age, gender, inpatient acute or rehabilitation length of stay, admission, discharge, or change in motor Functional Independence Measure (FIM) interval measures, or rehabilitation costs. Four of the 5 patients with ligamentous knee injuries were successfully managed nonoperatively. A case illustrating longitudinal management is presented. CONCLUSIONS: TBI and ligamentous knee injuries, in particular ACL injuries, are common comorbidities after PVMVC. Physicians must maintain a high index of suspicion for ligamentous knee injuries in this population, particularly when a tibial plateau fracture is present. TBI patients with and without ligamentous knee injuries can have comparable functional outcomes when the ligament injuries are identified and appropriately managed, without incurring undue cost or length of inpatient rehabilitation.

Hemiplegic gait. Relationships between walking speed and other temporal parameters.

It has been asserted that speed alone is an effective indicator of the degree of gait abnormality. To determine the validity of this assertion, relationships between velocity and 18 other temporal gait parameters were determined in 25 patients with a first hemispheric stroke resulting in hemiplegia or hemiparesis of at least one month duration. Gait characteristics were recorded using footswitchs connected to a portable computerized monitoring device. Velocity was found to be significantly correlated with cadence, mean cycle duration, mean cycle length, hemiplegic limb stance phase duration, nonhemiplegic limb stance phase duration and percent, nonhemiplegic limb swing phase percent, double support phase duration and percent, hemiplegic limb swing/stance phase ratio, nonhemiplegic limb swing/stance phase ratio, and swing phase symmetry ratio but not with the hemiplegic limb stance phase percent, hemiplegic limb swing phase duration and percent, nonhemiplegic limb swing phase duration, stance phase symmetry ratio, and overall asymmetry ratio. Velocity is related to most, but not all, of the other temporal measures of hemiplegic gait. A comprehensive gait evaluation should also include characterization of the degree of asymmetry and descriptions of individual phase durations and proportions (particularly hemiplegic stance and swing percentages).

Stability of drugs of abuse in urine samples stored at -20 degrees C.

Isolated studies of the stability of individual drugs of abuse have been reported. However, few have evaluated stability in frozen urine samples stored for 12 months. We have determined the stability of 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (9-COOH-THC), amphetamine, methamphetamine, morphine, codeine, cocaine, benzoylecgonine, and phencyclidine in 236 physiological urine samples. Following the initial quantitative analysis, the samples were stored at -20 degrees C for 12 months and then reanalyzed. All drug concentrations were determined by gas chromatographic-mass spectrometric methods with cutoff concentrations of 5 ng/mL for 9-COOH-THC and phencyclidine and 100 ng/mL for each of the other drugs. The average change in the concentrations of these drugs following this long-term storage was not extensive except for an average change of -37% in cocaine concentrations.

Clinical and histologic evaluation of the prolapsed third eyelid gland in dogs.

Eighteen prolapses of the gland of the third eyelid in 17 Beagles were randomly allocated to 3 groups, which included nontreated (group 1, n = 6), excised (group 2, n = 4), and surgically repositioned (group 3, n = 8) glands. A schirmer tear test (STT) was performed on affected and normal (control) eyes for 5 consecutive days on weeks 0 (baseline), 2, 4, 6, 8, 10, 12, 16, 18, 20, and 24. All prolapsed third eyelid glands were excised and examined histologically. Ten female and 7 male Beagles were used in the prospective study. Mean age at prolapse was 35.1 weeks (range, 6 to 89 weeks). Control STT data revealed a population mean of 22.2 +/- 2.1 mm/min. Complications developed in 4 of 6 eyes when the gland was allowed to remain in a prolapsed position. Complications for group-1 eyes were significantly (P < 0.005) greater than those for eyes in groups 2 and 3 (0 of 12). Comparison of affected and control eye baseline data revealed decreased STT values for eyes with prolapsed glands (P < 0.01). Mean differences between affected and control eyes were 2.2, 2.0, and 3.4 mm/min for groups 1, 2, and 3, respectively. A significant (P < 0.001) decrease in lacrimation (0.2 to 3.1 mm/min) in group-2 eyes was detected after removal of the gland. Tear production for affected eyes of nontreated dogs fluctuated above and below that of control eyes prior to excision of the prolapsed gland of the third eyelid; however, with time, affected and control eye STT values were not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

Ocular neoplasia.

Except for two neoplasms, notably SCC and sarcoid, ocular and periocular tumors are uncommon in horses. The practitioner must accurately determine the type of tumor by histopathology so appropriate treatment and a legitimate prognosis can be offered. The first attempt at treatment has the greatest chance to result in a cure; an aggressive treatment regimen therefore should be selected from the start.