Poly(2-hydroxyethyl methacrylate) surface chemistry and modulus differentially modulate neutrophils and lens epithelial cells-possible implications in cellular responses to intraocular lenses.

During cataract surgery, diseased lenses in the eye are surgically removed and replaced with polymeric artificial intraocular lenses (IOLs). Patients can experience a complication called posterior capsular opacification (PCO) that is corrected through the removal of part of the posterior capsule using a neodymium: yttrium-aluminum-garnet (Nd-YAG) laser to restore the optical path. These interventions have increased costs and can damage the retina and the IOL. PCO develops when lens epithelial cells (LECs) proliferate, migrate, and undergo epithelial-to-mesenchymal transition. Neutrophils involved in the immune response triggered during implantation impact LEC behavior and produce damaging neutrophil extracellular traps (NETs). In this research, poly(2-hydroxyethyl methacrylate) (PHEMA) -based disks were synthesized with varying amounts of comonomer (HEMA with 0, 2, and 12 mol% MMA) and functionalized with carboxyl and amine groups, yielding nine different hydrogels. Material and chemical properties of the disks were characterized, and neutrophil-like HL60 cells and B3 LECs were incubated with the disks. HL60 cell behavior was more strongly influenced by chemical functionalization than by mechanical properties with increases in adherence and NET accumulation. Conversely, the behavior and viability of B3 LECs were more strongly influenced by mechanical properties with increases in cell adhesion and α-SMA expression with increasing compressive moduli. Interestingly, B3 LECs had decreased viability and increased α-SMA expression when cultured on PHEMA2 disks pretreated with isolated NETs. Critical to the understanding of PCO and its prevention are both surface chemistry and mechanics as well as the inflammatory response.

Population-based p16 and HPV positivity rates in oropharyngeal cancer in Southeast Scotland.

We assessed a population-based cohort of patients diagnosed with oropharyngeal squamous cell carcinoma in Southeast Scotland over 13 months. p16 and human papilloma virus (HPV) expression were determined, and correlated with stage, treatment, smoking and alcohol history, and disease outcomes. Retrospective analysis was performed on 60 patients. p16 immunohistochemistry and HPV genotyping were performed on formalin-fixed paraffin-embedded tissues. HPV infection (as defined by p16 positivity and/or HPV PCR positivity) was identified in 57% of samples, while dual positives were detected in 45% of cases. HPV16 was most prevalent of the HPV types and was associated with 90% of positive samples. Cause-specific 1-year and 2-year survivals were 82.5% and 78.2%, respectively. The p16-positive and HPV-positive groups demonstrated significantly increased cause-specific survival in comparison with their negative counterparts.

Photosensitive controlled release with polyethylene glycol-anthracene modified alginate.

Covalent modification of alginate with polyethylene glycol-conjugated anthracene molecules has the potential to both stabilize the alginate and act as a photosensitive crosslinker. Release studies with Coomassie Blue show lengthy release times from the alginate photogels that extend past 70 days with, for example, 17% versus 27% release at 1750 h (73 days) for photogels with and without 365-nm UV light treatment for 30 min at 10 mW/cm(2) in the initial release period. Photocrosslinking of the photogels after loading effectively "locks" in drug compounds to control their release. Effective crosslinking densities and controls of polyethylene glycol-crosslinked alginate and physically crosslinked calcium alginate gels suggest strong interactions between Coomassie Blue and both alginate and anthracene. Photogels containing anthracene-capped star-polyethylene glycol show increased photosensitivity with modified release profiles. Ultimately, the covalent modification of alginate with photoactive crosslinkers has the potential to produce a long-term, photosensitive, controlled release system.

Extended release of high pI proteins from alginate microspheres via a novel encapsulation technique.

Alginate has potential as a matrix for controlled delivery of protein-based drugs that require site-specific long-term delivery. In the current work albumin, lysozyme and chymotrypsin were encapsulated into alginate microspheres using a novel method that involved soaking the microspheres in a protein-containing NaCl solution. This was followed by recrosslinking with calcium chloride. High pI proteins also appeared to physically crosslink the sodium alginate which resulted in more sustained release. Release was affected by the nature of the releasate solution. In TRIS buffered saline, the high pI proteins chymotrypsin and lysozyme showed sustained release lasting over 150 h. Release into 0.15% NaCl led to relatively constant release of lysozyme and chymotrypsin over more than 2000 h; reduction of the releasate volume lengthened the lysozyme release to greater than 8 months. Released lysozyme was shown to remain active for at least 16 days, in some cases with activity greater than 100% of the active control. This encapsulation technique can therefore be used to rapidly load alginate microspheres with proteins, with high isoelectric point proteins showing particular promise. Furthermore, the interactions between the high pI proteins and the alginate gel could potentially be exploited to generate new protein delivery systems.

Bulimia nervosa: an update and treatment recommendations.

Bulimia nervosa is a common eating disorder in adolescent women. Biological, psychological, and social factors are implicated in onset and important in treatment. Diagnosis of the syndrome, but not its subtypes, can be made well using the DSM-IV system. Screening tools, laboratory findings, and physical findings can be helpful in making the diagnosis. Comorbid disorders include affective disorders, addictive disorders, anxiety disorders, personality disorders, and anorexia nervosa. The etiology of bulimia nervosa is complex, with biologic, psychological, social, and family factors, which likely differ somewhat from patient to patient. Treatment, accordingly, should be comprehensive, individualized, and multifaceted. Many patients respond well to the use of an antidepressant, and cognitive-behavioral therapy is a useful approach for many patients. Combining these two treatments seems to be a good strategy. Environmental and family issues also need to be addressed. Many patients are treated insufficiently. More research on bulimia nervosa specific to adolescence is needed.

Partial paternal uniparental disomy of chromosome 6 in an infant with neonatal diabetes, macroglossia, and craniofacial abnormalities.

Neonatal diabetes, which can be transient or permanent, is defined as hyperglycemia that presents within the first month of life and requires insulin therapy. Transient neonatal diabetes mellitus has been associated with abnormalities of the paternally inherited copy of chromosome 6, including duplications of a portion of the long arm of chromosome 6 and uniparental disomy, implicating overexpression of an imprinted gene in this disorder. To date, all patients with transient neonatal diabetes mellitus and uniparental disomy have had complete paternal isodisomy. We describe a patient with neonatal diabetes, macroglossia, and craniofacial abnormalities, with partial paternal uniparental disomy of chromosome 6 involving the distal portion of 6q, from 6q24-qter. This observation demonstrates that mitotic recombination of chromosome 6 can also give rise to uniparental disomy and neonatal diabetes, a situation similar to that observed in Beckwith-Wiedemann syndrome, another imprinted disorder. This finding has clinical implications, since somatic mosaicism for uniparental disomy of chromosome 6 should also be considered in patients with transient neonatal diabetes mellitus.

Implicit motor sequence learning is represented in response locations.

Previous work (Willingham, 1999) has indicated that implicit motor sequence learning is not primarily perceptual; that is, what is learned is not a sequence of stimuli. Still other work has indicated that implicit motor sequence learning is not specific to particular muscle groups or effectors. In the present work, we tested whether implicit motor sequence learning would be represented as a sequence of response locations. In Experiment 1, learning showed very poor transfer when the response locations were changed, even though the stimulus positions were unchanged. In Experiment 2, participants switched their hand positions at transfer, so that one group of participants pushed the same sequence of keys but used a different sequence of finger movements to do so, whereas another group pushed a different sequence of keys but used the same sequence of finger movements used at training. Knowledge of the sequence was shown at transfer only if the sequence of response locations was maintained, not the sequence of finger movements.

Steroid-induced depressive psychosis responsive to electroconvulsive therapy.

We report the case of a 15-year-old girl with acute lymphoblastic leukemia who developed a severe steroid-induced depression, which was rapidly responsive to ECT. This report adds to the growing body of literature supporting ECT as a safe and effective treatment of affective and psychotic disorders in children.

Functional disorders in children and adolescents: diagnostic considerations.

OBJECTIVE: To describe the advantages of a nosologic approach to "functional" illness and its benefit in planning treatment for such illnesses. DESIGN: A review of common functional syndromes occurring during childhood and adolescence in presented. RESULTS: The functional versus "organic" dualism in pediatrics and family practice is not heuristic. The biopsychosocial model allows a more useful approach to nosology and treatment planning. An approach to such a clinical conceptualization is give. Several case examples are provided. CONCLUSION: Patients with functional syndromes should be assessed with specific diagnostic criteria rather than criteria of exclusion.

Bulimia nervosa and associated alcohol abuse among secondary school students.

Four adolescent student populations (totalling 686 girls and 705 boys) completed confidential questionnaires (98.6% response rate) concerning bulimia nervosa and alcohol abuse. All of the DSM-III-R criteria for bulimia nervosa were met by 2.0% of the girls and 0.1% of the boys. On the basis of score greater than or equal to 42 on the Adolescent Alcohol Involvement Scale, 12.5% of all girls and 9.2% of all boys were alcohol abusers. Our results suggest a significant association between bulimic behavior and alcohol abuse in this female population. Other factors associated with bulimic behavior included high maternal vocational status, high socioeconomic class (girls only), high weight for age and height, and low personal ideal weight. Other factors associated with alcohol abuse included high maternal vocational status, low paternal vocational status and education, low socioeconomic class (boys only), low grade point average, high age, and high birth order.

The dexamethasone suppression test in bulimia before and after successful treatment with desipramine.

Recent reports have suggested that normal-weight bulimic patients without clinical evidence of major depressive disorder will have an abnormal response to dexamethasone. Of 23 normal-weight bulimic patients without clinical evidence of major depressive disorder, 11 had abnormal results on their dexamethasone suppression tests (DSTs). This finding closely matches those of other reports. After successful treatment with desipramine, repeat DSTs showed conversion to normal suppression in 6 of the 7 patients tested. Pretreatment DST results failed to predict the response to medication. The striking similarity of these findings to those reported in patients with major depression suggests that bulimia may be a consequence or an equivalent of major affective disorder.

Treating bulimia with desipramine. A double-blind, placebo-controlled study.

A controlled study in patients with bulimia demonstrated a significant benefit from desipramine hydrochloride treatment (91% decrease in binge frequency) in contrast to the results from a placebo (19% increase in frequency). When patients originally taking the placebo crossed over to desipramine therapy, their frequency of binges decreased 84%, so that the overall improvement was 87% fewer binges. Global clinical status improved 3.5 scales, Zung depression scores improved 8.0 points, and a bulimia symptom scale improved 14.7 points. Fifteen (68%) of 22 patients attained complete abstinence from binge eating and purging. The presence or absence of previous episodes of anorexia nervosa did not influence the treatment response. One-month follow-up data indicated persistence of the benefit attained.

Human growth hormone in psychiatric disorders.

The authors review some features of the neuroendocrine regulation and neuropharmacologic manipulation of human growth hormone and then discuss some of the data that suggest that this hormone system might be involved in various psychiatric disorders. While emphasis is put on alcoholism and the affective disorders, the effects of stress, psychosocial deprivation and malnutrition are briefly discussed, as well. The possibilities and limitations of the psychoendocrine approach to psychiatric illnesses as exemplified by the growth hormone system are emphasized.