Three-dimensional control of light in a two-dimensional photonic crystal slab.

Optoelectronic devices are increasingly important in communication and information technology. To achieve the necessary manipulation of light (which carries information in optoelectronic devices), considerable efforts are directed at the development of photonic crystals--periodic dielectric materials that have so-called photonic bandgaps, which prohibit the propagation of photons having energies within the bandgap region. Straightforward application of the bandgap concept is generally thought to require three-dimensional (3D) photonic crystals; their two-dimensional (2D) counterparts confine light in the crystal plane, but not in the perpendicular z direction, which inevitably leads to diffraction losses. Nonetheless, 2D photonic crystals still attract interest because they are potentially more amenable to fabrication by existing techniques and diffraction losses need not seriously impair utility. Here we report the fabrication of a waveguide-coupled photonic crystal slab (essentially a free-standing 2D photonic crystal) with a strong 2D bandgap at wavelengths of about 1.5 microm, yet which is capable of fully controlling light in all three dimensions. These features confirm theoretical calculations on the possibility of achieving 3D light control using 2D bandgaps, with index guiding providing control in the third dimension, and raise the prospect of being able to realize unusual photonic-crystal devices, such as thresholdless lasers.

Polarization-sensitive subwavelength antireflection surfaces on a semiconductor for 975 nm.

We present the results of subwavelength antireflection surfaces etched into GaAs for use at 975 nm. These surfaces comprise linear gratings with periods less than the wavelength of light in GaAs. The structure appears as a homogeneous birefringent film. For one of the two polarizations, the film is directly analogous to the well-known quarter-wavelength antireflection coating. For the other polarization there is little effect on the surface reflectivity.

High-efficiency subwavelength diffractive optical element in GaAs for 975 nm.

We have fabricated subwavelength diffractive optical elements with binary phase profiles for operation at 975 nm. The individual surface-relief features of the elements are smaller than the wavelength of light in the material. By modulating the size and spacing of the features we form artificial, gradient, effective index-of-refraction surfaces. The blazed transmission gratings were designed with rigorous coupled-wave analysis and fabricated by direct-write electron-beam lithography and reactive ion-beam etching in GaAs. The gratings have minimum features 63 nm wide. Transmission measurements show 85% diffraction efficiency into the first order.

Dermatoglyphics in sudden infant death syndrome.

An analysis of digital and palmar dermatoglyphic patterns was conducted in 173 victims of the sudden infant death syndrome (SIDS). The results expose four dermatoglyphic regions with pattern frequencies differing from those in a control population. These are an excess of Sydney creases, hypothenar patterns, open fields (with fewer vestiges) in interdigital region IV, and arches on all digits (females only). These findings indicate a genetic or early intrauterine environmental influence in SIDS infants. An increased incidence of dysmorphism and anomalies including recognition of specific syndromes support this contention. One could speculate that these dermatoglyphic deviations reflect specific genotypes and/or phenotypes particularly vulnerable to postnatal challenges. Differences in multiple dermatoglyphic categories support the concept of heterogeneity of the SIDS population and multicausality of SIDS.

Down syndrome: patterns of disturbed lung growth.

Abnormal pulmonary development characterized by decreased alveolar complexity has been previously reported in patients with Down syndrome. We investigated the state of pulmonary development and found several undescribed patterns of disturbed lung growth. The axial branches of intrasegmental airways were counted in 13 Down syndrome patients; in nine, airway generation was reduced by 25% or more of the predicted number. The radial alveolar counts were evaluated in 11 lungs: five were 143% to 162% above expected (four to above adult values), five were as expected, and one was below expected (82%). No correlation was found between airway number and radial alveolar count. Our finding of the reduction in airway branching in the lungs of patients with Down syndrome suggests interference with development before birth. Disturbances in alveolar multiplication are also found.

Improved survival for children with anaplastic Wilms' tumors.

Combined modality treatment has resulted in cure rates of approximately 80% for children with Wilms' tumor. According to the National Wilms' Tumor Studies (NWTS), a group of patients with histologic features of anaplasia or sarcomatous Wilms' tumors (malignant rhabdoid tumors and clear cell sarcomas) were less responsive to vincristine and actinomycin. The survival rate of patients in this group with unfavorable histologic conditions was 54% compared with 90% for those with favorable histologic conditions. We have reviewed 80 consecutive cases of Wilms' tumor treated with a minimum follow-up interval of 5 years. Two pathologists independently reviewed all histologic specimens that were initially classified as having unfavorable histologic conditions and specimens from children with favorable histologic conditions who subsequently relapsed. One of 13 children with favorable histologic conditions had recurrent disease that was found to have unfavorable histologic conditions on rereview. All five patients with sarcomatous Wilms' tumor had a rapidly progressive course. Treatment of eight children with anaplastic Wilms' tumor with vincristine, actinomycin, cyclophosphamide, and abdominal radiation resulted in good disease-free and overall survival rates (5-year survival rate, 87.5%) that were not significantly different from children with tumors having favorable histologic conditions (5-year survival rate, 94%). All children with sarcomatous histologic conditions, however, did not to respond.

Osteosarcoma in young children.

The clinicopathologic features of osteosarcoma in 12 children younger than 16 years of age treated at The Children's Hospital and Dana-Farber Cancer Institute, Boston, during a 70-year time period are presented. Only one of six children treated before 1972 is a long-term survivor. Four of six children (67%) treated after 1972 are disease-free with an average follow-up of 8.8 years. The year 1972 marked the onset of use of effective chemotherapy in osteosarcoma, namely, high-dose methotrexate and leucovorin rescue. It would appear that the pathologic features and behavior of osteosarcoma in young children is similar to that of osteosarcoma in older children and adolescents. A combination of complete (wide) surgical resection or amputation and aggressive chemotherapy offers the best chance of long-term survival.

Delayed central nervous system myelination in the sudden infant death syndrome.

This study was designed to assess whether development of the central nervous system (CNS) is delayed in victims of the sudden infant death syndrome (SIDS). We selected the parameter of myelination because it is a continuously changing and readily accessible marker of CNS development in the SIDS age-range. We assessed myelination blindly in 61 SIDS and 89 autopsy controls. In 62 sites the degree of myelination was visually graded in myelin-stained histological sections on an ordinal scale of 0-4 using the inferior cerebellar peduncle as an internal standard of degree 3. Cases were stratified by postconceptional age at death and SIDS and controls were compared with respect to myelin degree at each site. Significantly delayed myelination (p less than 0.05) occurred in the SIDS group in 25 of the 62 sites examined. Hypomyelination affected fiber systems in which myelination is initiated before or after birth and which myelinate with different tempos and preferentially affect pyramidal and cerebellar (somatomotor) and prefrontal-temporal-limbic (visceromotor) systems. Hypomyelination was not associated with individual clinicopathologic variables in the SIDS group. Somatic growth and brain weight were significantly greater in SIDS than controls. Therefore, we suggest that SIDS is associated with a developmental CNS disorder. Although delayed CNS myelination most likely shares a common antecedent with sudden death and is not its cause, the role of somato- and viscero-motor systems in central cardiorespiratory control and arousal warrants further analysis in SIDS.

Bone sarcomas as second malignant neoplasms following childhood cancer.

This study explores the relationship between histologic variants of bone sarcomas and previous therapy in patients in whom an unrelated malignant neoplasm had been diagnosed during childhood. Sarcomas of bone were the most common second malignant neoplasm (SMN) reported to the Late Effects Study Group, a 13-institution consortium consisting of pediatric oncology centers from western Europe, Canada, and the United States. The authors attempted to relate the histologic subtypes of the 91 bone tumors to clinical factors such as previous therapy and genetic predisposition because morphologic variants have been shown to have biologic significance in other tumors and may have etiologic import. The literature concerning the subtypes of bone tumors, clinical and experimental, is also reviewed. The authors also investigated the effect of several factors on the time interval from the first diagnosis to the SMN (i.e., the bone sarcoma). Anthracyclines significantly shortened the interval by about 3 years. The primary diagnosis also significantly affected the interval, with leukemia/lymphomas having the shortest interval and retinoblastoma the longest. The authors could not demonstrate any significant relationship between morphologic characteristics of the osteosarcoma and predisposing conditions. However, lesions diagnosed as chondrosarcoma and malignant fibrous histiocytoma occurred almost exclusively in patients who had received radiation therapy to the site in which the SMN developed.

Flow cytometric evaluation of multicystic dysplastic kidneys.

The most appropriate management of the multicystic dysplastic kidney remains controversial. At issue is the long-term risk of the development of malignancy in the multicystic dysplastic kidney. The association between renal dysplasia and neoplasia has not been confirmed, with only 6 cases of malignancy reported. Nephroblastomatosis, a probable precursor of Wilms tumor, has been found in 5 to 7% of the cases of multicystic dysplastic kidney when specifically sought. In an attempt to determine whether a relationship exists between renal dysplasia and neoplasia in terms of abnormalities of cellular deoxyribonucleic acid content we performed flow cytometric evaluation on 30 formalin fixed, paraffin embedded archival specimens of multicystic dysplastic kidneys. None of the kidneys had evidence of malignancy. Nuclear deoxyribonucleic acid ploidy studies were performed on single dissociated nuclei prepared by the technique of McLemore and associates and stained with propidium iodide. All specimens demonstrated a diploid pattern of deoxyribonucleic acid, including 3 specimens with nephroblastomatosis or extensive papillary growth, and no specimen demonstrated a tetraploid or aneuploid pattern. The mean G0/G1 fraction was 85.94% (standard deviation 4.59) and the mean S/G2/M fraction was 12.54% (standard deviation 4.72). These findings do not support or negate the potential for neoplasm associated with multicystic dysplastic kidney, since a diploid deoxyribonucleic acid pattern does not eliminate the possibility of the future development of malignancy.

myc gene amplification and expression in primary human neuroblastoma.

Although N-myc amplification in neuroblastomas correlates with poor prognosis, not all neuroblastomas which fail to respond to therapy have N-myc amplification. To determine whether other modes of myc gene activation underlie progression of some neuroblastomas, 45 were analyzed for amplification of N-myc, c-myc and L-myc and 26 were studied for transcription of these oncogenes. N-myc amplification was found in 6 of 45 tumors; no tumor had amplification of c-myc or L-myc. Transcription of both N-myc and c-myc occurred in 21 of 26 neuroblastomas. No tumor without N-myc amplification had a level of N-myc expression near that of a tumor or cell line with amplification. One tumor with N-myc amplification was the only specimen with N-myc but not c-myc expression. Five samples had c-myc but not N-myc expression; all had histological features of ganglioneuroma. DNA index did not correlate with myc gene amplification or expression. It is concluded that N-myc and c-myc are commonly expressed in primary untreated neuroblastomas, but in the absence of N-myc amplification, expression of these genes does not appear to correlate with disease progression.

Characterization of airway mucus from a fatal case of status asthmaticus.

We used density gradient methods to analyze mucus recovered from the airways of a patient who died from status asthmaticus. At postmortem the mucus that plugged the length of the bronchial tree could only be removed by cutting with forceps. It was dispersed in cesium bromide (CsBr) and examined in the analytical ultracentrifuge. Surprisingly, no macromolecular component was seen in the buoyant density region typical of mucus glycoprotein (at 1.5 g/ml). The gelatinous material migrated to the region of lowest density, typical of lipids, and thin-layer chromatography indicated that besides neutral lipids, a variety of phospho- and glycolipids (including gangliosides) were present. The residue left after the lipid extraction contained all sugar components of mucus glycoprotein, and alkaline borohydride cleaved oligosaccharides three to 12 sugars long, indicating that the sugars were O-glycosidically linked as in mucus glycoproteins. Prior desulfation of the residue increased the number of oligosaccharides released by borohydride; analysis showed the presence in these of components (glucose, methylmannuronate) not present in epithelial glycoprotein. A trace component of high buoyant density was also present: Glucose was the predominant component in this, but glycoprotein sugars were also present. The above results suggest that in status asthmaticus plugging of the airways with mucus can occur even in the absence of typical epithelial glycoprotein and that lipids play a crucial role in such plugging.

Radiologic and pathologic abnormalities of the trachea in older patients with cystic fibrosis.

The possibility of tracheal enlargement in older patients with cystic fibrosis was investigated by examining chest radiographs of 42 living adults (age range, 30-45 years) who had the disease and by performing postmortem studies (anatomic and histologic) on the tracheas of older adolescents and young adults (age range, 15-33 years) who died with the disease. Anteroposterior tracheal diameters were enlarged in 41 of the living adults. The average diameter was 1.3 +/- 0.9 SD standard deviations above the mean for normal subjects. These increases did not correlate with severity of pulmonary disease as judged radiographically. Enlargement seemed to have developed slowly, over many years or decades. A few tracheas were grossly irregular in outline. One patient had a severely increased transverse diameter of 4.7 standard deviations above the normal mean. The average transverse diameter was 0.3 +/- 1.1 SD standard deviations above the normal mean. The tracheas of adults and older adolescents who had died with cystic fibrosis were abnormally flaccid. Some collapsed suddenly during deflation. Microscopic examination showed instances of severe inflammation, focal epithelial metaplasia, hypertrophy and hyperplasia of the mucous glands, degenerative changes in the muscle of the pars membranacea, and death of cartilage cells. The structural changes shown histologically and the many decades of frequent, vigorous coughing may be important in the enlargement of these tracheas and their flaccidity.

Pneumatosis intestinalis in cystic fibrosis.

We retrospectively reviewed the clinical and radiographic findings in patients with pneumatosis intestinalis (PI), who were identified among 441 patients with cystic fibrosis. Since 1944, the age at onset and the incidence of PI have increased. Pneumomediastinum, pneumothorax, or pulmonary interstitial emphysema was found in 95% of patients with PI compared with 62% of patients without PI. The type, distribution, and severity of PI often changed with time. PI is correlated with the development of obstructive pulmonary disease, which facilitates air dissection into interstitial spaces. Dissection of air is often clinically silent and tends to be self-perpetuating.

Nonexpression of cartilage type II collagen in a case of Langer-Saldino achondrogenesis.

A lethal short-limbed dwarfism was diagnosed at autopsy as the Langer-Saldino variant of achondrogenesis by radiological, histological, and gross pathological criteria. Cartilage was obtained for biochemical and ultrastructural analyses from the ends of long bones, from ribs and from a scapula of the newborn infant. At all sites, it had an abnormal gelatinous texture and translucent appearance. Biochemical analyses of the cartilages to identify pepsin-solubilized collagen alpha-chains and collagen-specific CNBr-peptides failed to detect type II collagen at any site where it would normally be the main constituent. Instead, type I was the predominant collagen present. However, three cartilage-specific minor collagen chains identified as 1 alpha, 2 alpha, and 3 alpha chains by their electrophoretic mobility were present at about 10% of the total collagen. Cartilage-specific proteoglycans also appeared to be abundant in the tissue judging by its high hexosamine content and high ratio of galactosamine to glucosamine. The findings indicate that a chondrocyte phenotype had differentiated but without the expression of type II collagen. In addition to the skeletal abnormalities, the severe pulmonary hypoplasia was also felt to be directly related to the underlying pathology in collagen expression. The term chondrogenesis imperfecta rather than achondrogenesis should be considered a more accurate description of this and related conditions.