Glass transition of nanometric polymer films probed by picosecond ultrasonics.

The possibility to measure the glass transition temperature in poly(methyl methacrylate) (PMMA) films by picosecond ultrasonics with thicknesses ranging from 458 nm to 32 nm is demonstrated. A shift of the longitudinal acoustic eigenmodes towards lower frequencies with temperature is observed accompanied by a change in the temperature-frequency slopes at the glass transition temperature. The contributions to the frequency shift from changes in film thickness and sound velocity are discussed and the latter is extracted below the glass transition temperature. Finally, the advantages and disadvantages of the current approach in a comparison to other methods based on acoustic measurements in the GHz regime are reviewed.

Interface Adhesion and Structural Characterization of Rolled-up GaAs/In0.2Ga0.8As Multilayer Tubes by Coherent Phonon Spectroscopy.

We present a detailed experimental and theoretical study of the acoustic phonon modes in rolled-up multilayers with thickness of the layers in the nanometre and diameters in the micrometre range. We compare our results to planar, unrolled multilayers grown by molecular beam epitaxy. For the planar multilayers the experimentally obtained acoustic modes exhibit properties of a superlattice and match well to calculations obtained by the Rytov model. The rolled-up superlattice tubes show intriguing differences compared to the planar structures which can be attributed to the imperfect adhesion between individual tube windings. A transfer matrix method including a massless spring accounting for the imperfect adhesion between the layers yields good agreement between experiment and calculations for up to five windings. Areas with sufficient mechanical coupling between all windings can be distinguished by their acoustic mode spectrum from areas where individual windings are only partially in contact. This allows the spatially resolved characterization of individual tubes with micrometre spatial resolution where areas with varying interface adhesion can be identified.

A new family of lipolytic plant enzymes with members in rice, arabidopsis and maize.

We have noted a striking similarity between the sequences of proteins in a novel family of lipases we recently reported [Upton, C. and Buckley, J. T. (1995) Trends Biol. Sci. 20, 178-9] and more than 120 sequences from the database of Expressed Sequence Tags (dbEST) which correspond to at least 30 unique genes from arabidopsis, rice and maize. A cDNA (Arab-1) corresponding to one of these sequences was isolated, sequenced and translated. There was significant similarity to sequences in the new lipase family over the entire open reading frame of Arab-1 and when expressed in E. coli, the gene product was lipolytic. Arab-1 and genes for some of the other plant proteins appear to be differentially expressed. They may play a role in the regulation of lipid metabolism during plant development.

Ocular lesions associated with dissemination of type 2 herpes simplex virus from skin infection in newborn rabbits.

The subcutaneous inoculation of the backs of New Zealand white rabbits 17 to 34 hr old with 10(3) 50% tissue culture infection dose (TCID50) of type 2 herpes simplex virus (HSV-2) induced cutaneous lesions within 24 hr, foci of disseminated infection in many organs (including the eye) on day 3 and thereafter, and the death of the animals on day 5 with infection of the central nervous system. Infectious HSV-2 could be isolated from the mononuclear cells and plasma of the peripheral blood, indicating the active role of both elements in the dissemination of the virus. Infectious HSV was also recovered from the corresponding sensory ganglia of the skin lesion (the cervicothoracic ganglia) as early as 2 days after the subcutaneous inoculation of the virus. About 40% of the animals developed ocular consisting of retinal folds with or without degenerative changes, Iritis and choroiditis also developed in some eyes. Infectious HSV-2 could be isolated from 33% of the eyes on days 4 and 5. Thus the newborn rabbit may serve as a suitable experimental animal for the study of HSV-2-induced chorioretinitis in the human newborn.

Low yield of bacterial stool culture in children with nosocomial diarrhea.

OBJECTIVE: To determine whether bacterial stool cultures (BSC) are useful in initial evaluation of children with symptoms of nosocomial diarrhea. To answer this question we performed a retrospective record review to determine the yield of BSC in children who developed diarrhea after the third hospital day (HD-3). METHODS: The hospital computer record keeping system was utilized to compile the result of BSC collected from children and adolescents ages 0 to 20 years between January 1, 1988, and October 31, 1996. All specimens were analyzed for Salmonella, Shigella, Yersinia and Campylobacter. We reviewed hospital charts of all children who developed a positive BSC beyond HD-3 to determine the time of onset of diarrhea and clinical circumstances. RESULTS: A total of 11 516 BSCs were submitted from 9262 children during the 8 1/2-year period. Five hundred sixty-eight (6.6%) of 9262 children had at least 1 positive BSC. Two thousand five hundred seventy-two children had the first BSC submitted after HD-3 and 13 (0.5%) of these children had a positive result. Chart review of these 13 children demonstrated that 6 had onset of diarrhea during the first 3 hospital days. Therefore only 7 children met our criteria for having nosocomially acquired diarrhea caused by a bacterial pathogen. Children whose first BSC was submitted after HD-3 accounted for 3767 (46%) of the total 8126 inpatient BSCs and in excess of $21000 annually in patient billing charges. CONCLUSION: In the absence of a known exposure the isolation of a bacterial pathogen from the stool of children with onset of diarrhea beyond HD-3 is a rare event. Under most circumstances BSC should not be part of the initial evaluation of children with symptoms of nosocomial diarrhea.

Medication errors result in costly claims for ophthalmologists.

Medication errors are a frequent cause of medical malpractice claims. Because serious injury often results, medication errors can be costly to defend, indemnify or settle. A review of five closed claims involving glucocorticoids, corticosteroids, antibiotics and silver nitrate offers insight into how ophthalmologists can protect themselves against medication malocurrences.

Risk management lessons from a review of 168 cataract surgery claims.

One hundred sixty-eight closed claims involving cataract procedures reported to Ophthalmic Mutual Insurance Company (OMIC) over a 10-year period were evaluated. Indemnity payments totaling more than $3 million were made in 37 cases. These 37 cases represented only 7% of all OMIC claims, but their total indemnity payment represented 24% of the total indemnity paid by OMIC during the 10-year period.

Liability issues associated with PRK and the excimer laser.

Given the elective nature of photorefractive keratectomy (PRK), the high expectations of patients, and misconceptions of the general public about refractive surgery, the use of the excimer laser for PRK opens the door to new liability risks for ophthalmologists and, in the comanagement environment, referring optometrists. The authors discuss informed consent, marketing, comanagement, and off-label use guidelines and protocols to help protect ophthalmologists against claims and better defend those that might arise.

Pyogenic granulomas of the cornea.

Pyogenic granulomas are vasoproliferative, inflammatory lesions composed of granulation tissue, which occur on cutaneous or mucosal tissues, often arising secondary to other processes such as trauma or infection. Conjunctival pyogenic granulomas are not rare, but corneal involvement is very unusual and can occasionally lead to problems in the differential diagnosis of corneal masses. We report three cases of pyogenic granuloma involving the cornea. The clinicopathologic features of these cases and a review of the literature on the ocular manifestations of this condition are presented.

Orbital haemorrhage and prolonged blindness: a treatable posterior optic neuropathy.

Two patients developed traumatic orbital haemorrhage resulting in prolonged blindness. Orbital decompression successfully reversed the visual loss, though both eyes had no light perception for at least 3 1/2 hours. The clinical findings suggest damage to the posterior optic nerve as cause of the visual loss. The optic nerve tolerance time to ischaemic injury may be longer than previously thought.

Metabolic and endocrine correlates of cognitive function in healthy young women.

OBJECTIVE: Obesity has been associated with cognitive decline in longitudinal studies of older individuals. We hypothesized that the cognitive sequelae of obesity may be detectable in the reproductive years. In addition, we explored the hypothesis that these associations may be mediated by the hormonal milieu. DESIGN AND METHODS: Of 49 young healthy lean and overweight women aged 20-45, we investigated the association between performance on a battery of cognitive tests, body composition parameters [body mass index, total fat, abdominal (visceral, subcutaneous, and total) adipose tissue, and muscle], and hormone levels (insulin, adiponectin, leptin, insulin-like growth factor 1 (IGF-1), estrogen, testosterone, and vitamin D). RESULTS: We found a significant negative association between both visceral adiposity and muscle, and performance in the domain of verbal learning and memory, after controlling for age and education. Other body composition parameters showed similar trends (0.05 < P < 0.10). Additionally, the degree of insulin resistance was negatively associated with executive function domain. None of the associations between the other hormones examined (adipokines, IGF-1, gonadal hormones, and vitamin D) and cognitive function were significant. CONCLUSION: These preliminary findings suggest a possible association between obesity and cognitive function in healthy young women of reproductive age. More research is warranted into the potential modulatory effect of insulin resistance on this association.

Determinants of IGF1 and GH across the weight spectrum: from anorexia nervosa to obesity.

CONTEXT: Chronic starvation is characterized by GH resistance, and obesity is characterized by decreased GH secretion. In both extremes, IGF1 levels may be low and androgen levels may be abnormal. OBJECTIVE: To investigate the determinants of IGF1 and GH across the weight spectrum in women. DESIGN: Cross-sectional study. SETTING: Clinical research center. STUDY PARTICIPANTS: In total, 32 women had participated in the study: 11 women with anorexia nervosa (AN), 11 normal-weight women, and 10 obese women of comparable mean age. INTERVENTION: None. MAIN OUTCOME MEASURES: Pooled hourly overnight serum samples assayed for IGF1, GH, estradiol (E(2)), testosterone, SHBG, insulin, free fatty acids, and trunk fat. RESULTS: Free testosterone was higher in obese women and lower in women with AN than in normal-weight women, and was the only independent (and positive) predictor of IGF1 levels, accounting for 14% of the variability (P=0.032) in the group as a whole. This relationship was stronger when obese women were excluded, with free testosterone accounting for 36% of the variability (P=0.003). Trunk fat accounted for 49% of the variability (P<0.0001) of GH, with an additional 7% of the variability attributable to E(2) (P=0.042) in the group as a whole, but was not a significant determinant of GH secretion when obese women were excluded. CONCLUSIONS: Free testosterone is a significant determinant of IGF1 levels in women across the body weight spectrum. In contrast, GH secretion is differentially regulated at the extremes of the weight spectrum.

Bioactive insulin-like growth factor-I in obesity.

CONTEXT: In obesity, total IGF-I is not reduced to the degree predicted by low GH levels, and free IGF-I levels are normal to high. Total and free IGF-I may not reflect IGF-I biological activity because immunoassays cannot account for the modifying effects of IGF binding proteins on interactions between IGF-I and its receptor. OBJECTIVE: The aim of the study was to investigate the biological activity of IGF-I in obesity. DESIGN AND SETTING: We conducted a cross-sectional study at a General Clinical Research Center. STUDY PARTICIPANTS: Thirty-four healthy women (11 lean, 12 overweight, and 11 obese) of comparable age (overall mean, 30.7 +/- 1.3 yr) participated in the study. INTERVENTION: There were no interventions. MAIN OUTCOME MEASURES: We measured bioactive IGF-I (as measured by a kinase receptor activation assay), IGFBP-1, and GH using 6-h pools of serum collected every 10 min for 24 h, and fasting IGF-I and IGFBP-3. RESULTS: Mean 24-h GH (R = -0.76; P < 0.0001), total IGF-I (R = -0.36; P = 0.040), and IGFBP-1 (R = -0.41; P = 0.017) levels were inversely associated with BMI, whereas bioactive IGF-I and IGFBP-3 levels were not. Mean bioactive IGF-I was similar in the groups [2.72 +/- 0.22 (lean), 3.10 +/- 0.32 (overweight), and 2.43 +/- 0.23 [corrected] (obese) microg/liter; overall P = 0.22]. Percentage bioactive IGF-I [(bioactive/total IGF-I) x 100] was higher in obese subjects than both lean and overweight subjects (P = 0.039). CONCLUSIONS: Despite low GH secretion in obesity and decreasing IGFBP-1 with increasing BMI, 24-h mean bioactive IGF-I levels are not reduced in obese women and do not correlate with BMI or IGFBP-1 levels. This argues against elevated bioactive IGF-I as the etiology of reduced GH secretion through a feedback mechanism in obesity.

Outcome of prenatally diagnosed congenital heart disease: an update.

The objective of this study was to compare the outcome of prenatally diagnosed congenital heart disease (CHD) in a recent time period with previously reported experience. All cases of fetal CHD during the time period 1993 to 1999 were analyzed in terms of their outcome. During this time frame, 408 cases of fetal CHD were detected. Of these, 84% of mothers were referred because of suspicion of a cardiac anomaly during an obstetric scan. The mean gestational age at diagnosis was 26 weeks. Termination of pregnancy occurred in 98 cases. There were 92 deaths in the continuing pregnancies and a survival rate of 60%. The detection rate of CHD prenatally continues to increase as obstetric screening for cardiac malformations becomes more widespread. Diagnostic categories continue to be skewed toward more complex forms of malformation, although comparisons with previous studies show some trends. In particular, there are proportionately fewer pregnancies with extracardiac malformations. In addition, the outcome in continuing pregnancies is substantially improved from previous reports.

Ectromelia virus virulence factor p28 acts upstream of caspase-3 in response to UV light-induced apoptosis.

Ectromelia virus (EV) virulence factor p28 (EVp28) is a member of a family of poxvirus proteins that are defined largely by the presence of a C-terminal RING finger motif and localization to virus factories within the cytoplasm of infected cells. Previously, overexpression of the Shope fibroma virus (SFV) homologue, N1R, in vaccinia virus (VV)-infected BGMK cells was found to inhibit virus-induced apoptosis. Here, we report that both EVp28 and overexpression of SFV N1R in poxvirus-infected HeLa cells protect specifically from UV light-induced apoptosis, but not from apoptosis induced by Fas or TNF. Further, we report that both VV and EV protect from apoptosis induced by UV, Fas and TNF. Immunoblot analysis indicates that EVp28 acts upstream of caspase-3, blocking activation of the protease in response to UV irradiation. Although no difference was found in replication of an EVp28(-) mutant virus, which expresses a truncated p28 protein lacking the RING motif, compared to EV wild-type in HeLa cells, UV irradiation of infected HeLa cells reduced the replication of the EV mutant compared with wild-type EV.

Shope fibroma virus RING finger protein N1R binds DNA and inhibits apoptosis.

Shope fibroma virus (SFV) N1R gene encodes a RING finger protein that localizes to virus factories within the cytoplasm of infected cells. Altered proteins, with deletions and site-specific mutations, were transiently expressed in vaccinia virus-infected cells to discern regions of the protein that are required for localization. We have determined that at least part of the RING finger region is necessary for localization but that the RING motif alone is not sufficient. A chimeric protein, however, in which the RING finger region of the herpes simplex virus-1 ICP0 protein replaces the SFV N1R RING motif does localize to virus factories. A region of five highly conserved amino acids at the amino terminus of SFV N1R is also critical for localization. We report that the SFV N1R protein binds double- and single-stranded DNA, suggesting a mechanism for localization, and that overexpression of this protein in vaccinia virus-infected cells reduces apoptosis-associated fragmentation of nuclear DNA.

Mapping herpes simplex virus type 1 latency-associated transcript sequences that protect from apoptosis mediated by a plasmid expressing caspase-8.

LAT (latency-associated transcript) is the only herpes simplex virus type 1 (HSV-1) transcript abundantly expressed during neuronal latency. LAT expression is required for the high reactivation phenotype of HSV-1 and this phenotype correlates with LAT's anti-apoptosis properties. LAT nucleotides 1 to 1499 inhibit caspase-8 (death receptor apoptotic pathway), but not caspase-9 (mitochondrial apoptotic pathway), -induced apoptosis as efficiently as larger LAT fragments. LAT sequences important for inhibiting caspase-8-induced apoptosis were also localized. The ability of LAT nucleotides 1 to 1499 to efficiently inhibit caspase-8-induced apoptosis correlates with the high reactivation phenotype of a mutant virus expressing just the first 1.5 kb of LAT (nucleotides 1 to 1499).