Harmonic generation from silicon membranes at visible and ultraviolet wavelengths.

Nonlinear silicon photonics offers unique abilities to generate, manipulate and detect optical signals in nano-devices, with applications based on field localization and large third order nonlinearity. However, at the nanoscale, inefficient nonlinear processes, absorption, and the lack of realistic models limit the nano-engineering of silicon. Here we report measurements of second and third harmonic generation from undoped silicon membranes. Using experimental results and simulations we identify the effective mass of valence electrons, which determines second harmonic generation efficiency, and oscillator parameters that control third order processes. We can then accurately predict the nonlinear optical properties of complex structures, without introducing and artificially separating the effective χ(2) into surface and volume contributions, and by simultaneously including effects of linear and nonlinear dispersions. Our results suggest that judicious exploitation of the nonlinear dispersion of ordinary semiconductors can provide reasonable nonlinear efficiencies and transformational device physics well into the UV range.

Chromosomal aberrations in blood lymphocytes of astronauts after long-term space flights.

PURPOSE: To analyse lymphocyte chromosomes from astronauts of MIR and EUROMIR missions. MATERIALS AND METHODS: Peripheral lymphocytes from seven astronauts before and after space flights were cultured and analysed for structural chromosomal aberrations. RESULTS: Chromosome-type but not chromatid-type aberrations were significantly elevated after space flights when compared to pre-flight values. In one astronaut two rogue cells were found. CONCLUSIONS: Overall the frequencies of aberrations were found to be correlated with estimated absorbed cosmic radiation doses.

Nonsteroidal antiinflammatory drug modulation of behavioral responses to intrathecal N-methyl-D-aspartate, but not to substance P and amino-methyl-isoxazole-propionic acid in the rat.

Antinociception by nonsteroidal antiinflammatory drugs, notably diclofenac and S(+)-ibuprofen, has traditionally been attributed to peripheral tissue cyclooxygenase inhibition. This study investigates the potential role of the nitric oxide system for the central antinociceptive effects of diclofenac, S(+)-, and R(-)-ibuprofen. Diclofenac and S(+)- but not R(-)-ibuprofen inhibited the behavioral response dose dependently, "biting, scratching, and licking (BSL)," induced by the spinal application of N-methyl-D-aspartate, but not that of amino-methylisoxazole-propionic acid or substance P. Diclofenac and S(+)-ibuprofen induced a parallel shift in the number of BSL responses and in the duration of the response in the behavioral model at their approximate median effective doses (diclofenac 1 mumol and S(+)-ibuprofen 5 mumol). Pretreatment with L-arginine, the natural substrate for the nitric oxide synthetase, antagonized diclofenac, and S(+)-ibuprofen-induced suppression of the biting, scratching, and licking response evoked by intrathecal N-methyl-D-aspartate. D-arginine did not antagonize the diclofenac- and S(+)-ibuprofen-induced antinociception. The study results indicate that analgesia after diclofenac and S(+)-ibuprofen involves a central mechanism which may add to the peripheral antinociceptive effect of these agents. The central action of diclofenac and S(+)-ibuprofen is partly mediated by an interaction with the N-methyl-D-aspartate receptor and nitric oxide-generating mechanisms.

Prevention of class III-induced proarrhythmias by flecainide in an animal model of the acquired long QT syndrome.

The influence of the class Ic agent, flecainide, on the incidence of class III-induced torsades de pointes was examined in an animal model of the acquired long QT syndrome. Twenty-four chloralose-anaesthetized rabbits were pretreated at random with flecainide or vehicle and subsequently given a concomitant infusion of methoxamine and the class III antiarrhythmic agent almokalant. In seven out of eight vehicle-treated rabbits, almokalant induced torsades de pointes which was preceded by a significant lengthening of the JTU interval (used as an indirect measure of ventricular repolarization time) by 55 +/- 9.2 msec. Flecainide dose-dependently reduced the incidence of almokalant-induced torsades de pointes. Hence, in a group of rabbits given a low dose (0.14 mumol/kg + 1.4 mumol/kg/hr) of flecainide, four out of eight animals experienced torsades de pointes (P = 0.1538 versus vehicle) whereas no case (n = 8) was observed after a higher dose (4.8 mumol/kg + 4.8 mumol/kg/hr, P = 0.0007). In the former group almokalant induced a maximal increase in the JTU interval not differing from that seen in the vehicle-treated group (58 + 12.1 msec, P > 0.05). Pretreatment with the high dose of flecainide, however, caused a significant attenuation of the almokalant-induced lengthening of the JTU interval (18 +/- 6.5 msec. P < 0.05). It is concluded that flecainide reduces the risk of proarrhythmia in the setting of delayed repolarization partially by attenuating the primary electrophysiological effect of class III agents.

Acetaminophen blocks spinal hyperalgesia induced by NMDA and substance P.

The hypothesis tested was that inhibition of the L-arginine-nitric oxide (NO) pathway may represent a potential central mechanism of action for acetaminophen (paracetamol). Spinal administration of N-methyl-D-aspartate (NMDA, 0.5 nmol), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA, 0.1 nmol) or substance P (SP, 0.5 nmol) to the rat provoked a specific behaviour characterized by biting, scratching and licking (BSL). This behaviour was antagonized by pretreatment with acetaminophen for NMDA and SP but not for AMPA. Further, the antinociceptive effect of acetaminophen was readily reversed by administration of the natural substrate for nitric oxide synthase (NOS), L-arginine, but not by D-arginine. This suggests that the analgesic effect of acetaminophen is related to inhibition of NO generation. Potential mechanisms for this may involve NMDA and SP. Our data suggest that a significant portion of the analgesic effect of acetaminophen, when used clinically, may be related to an interaction with the central nervous system L-arginine-NO pathway.

Localized inflammatory pulmonary disease in subjects occupationally exposed to asbestos.

In reviewing pathology materials from patients occupationally exposed to asbestos, we identified eight patients with either localized nodules in their lung or unusual pathologic changes. The chest radiographs of six patients showed isolated parenchymal nodules thought to represent primary neoplasms. In three cases, pathologic examination of these nodules showed intraluminal fibrosis and inflammation of the distal airways, a pattern of change frequently referred to as "bronchiolitis obliterans organizing pneumonitis." In each instance, asbestos bodies were present in association with the fibroinflammatory tissue. In one case, the nodule showed a desquamative interstitial pneumonitis type pattern, and asbestos bodies were present admixed with the alveolar macrophages and occasionally within their cytoplasm. In one case, the nodule was composed of nonspecific inflammation and fibrosis with focal bronchiolitis obliterans and frequent asbestos bodies scattered throughout the area of inflammation and fibrosis, and in another case, necrotizing inflammation association with Aspergillus fungal organisms was identified. Granulomatous inflammation was the dominant pulmonary pathologic change in one patient, and the other patient's lung biopsy specimen showed a diffuse lymphocyte-plasma cell interstitial pneumonitis. The cases reported suggest that asbestos may cause localized lesions in the lung that clinically and radiographically are misinterpreted as cancer and that pathologically show inflammation and fibrosis of the distal airways. In addition, our observations suggest that asbestos may cause granulomatous inflammation, a desquamative interstitial type pneumonitis, and a lymphocytic interstitial pneumonitis type pattern. Our conclusions that asbestos may cause these pathologic changes are supported by case reports in the clinical and pathologic literature, clinicopathologic studies, and by experimental studies.

Localization of the central antinociceptive effects of diclofenac in the rat.

The ethacrynic acid-induced writhing response (WR) in the rat was studied after microinjections of diclofenac 0.1 ng-1 microgram/0.5 microliter (0.32 pmol to 3.2 nmol) into several brain regions involved in control of nociceptive behavior. The WR was inhibited after injections into the periaqueductal grey matter (PAG), ventromedial thalamus (VM), medial preoptic area (MPA) and the nucleus raphe magnus (NRM). Morphine 50 ng/0.5 microliter (0.16 nmol) was used as a positive control and vehicle injections were performed as negative reference. After diclofenac, there was a dose-dependent reduction of the WR with a threshold dose of approximately 1-10 ng in all brain areas studied except the nucleus reticularis paragigantocellularis interna (NRPGi). Naloxone 50 ng/0.5 microliter (0.15 nmol) administered into the same site 30 min after diclofenac injection, antagonized the diclofenac-induced inhibition of the WR almost completely in PAG and VM. Previous results demonstrate a central, naloxone-reversible component in the analgetic action of diclofenac. A qualitatively similar, centrally induced inhibition of the WR may be elicited after injections into PAG, VM and NRM. Thus, in addition to its peripheral mechanism of action, the non-steroidal anti-inflammatory drug, diclofenac, has a central mechanism of action which directly or indirectly involves a central opioid component.

Endosalpingiosis as a source of psammoma bodies in a Papanicolaou smear. A case report.

Psammoma bodies are concentric, laminated structures produced by cross-sectioning the tips of calcified papillary formations and are usually associated with papillary carcinoma of the thyroid gland, meningiomas and serous papillary tumors of the ovary. These structures have occasionally been seen in cytologic smears obtained from women with endometrial or ovarian carcinoma. A woman had Papanicolaou smears that continued to show psammoma bodies for over two years, eventually leading to a hysterectomy. Even though the presence of psammoma bodies on a Papanicolaou smear should always alert the physician to the possibility of ovarian carcinoma, leading to a thorough search for this malignancy, a variety of benign conditions, such as endosalpingiosis, may also be associated with this finding.

Pretreatment serum levels of CA-125, carcinoembryonic antigen, tissue polypeptide antigen, and placental alkaline phosphatase, in patients with ovarian carcinoma, borderline tumors, or benign adnexal masses: relevance for differential diagnosis.

Pretreatment serum levels of the antigens CA-125, tissue polypeptide Antigen (TPA), carcinoembryonic antigen (CEA), and placental alkaline phosphatase (PLAP) were determined in samples from 295 women with adnexal masses. At laparotomy 48% of patients had epithelial ovarian carcinoma, 9% had tumors of low malignant potential, and 8% suffered from malignancies of other kinds. The sensitivity of CA-125 with 35 U/ml as the cutoff was 88% in women with ovarian carcinoma, but 74% among those with limited disease and 58% in borderline malignancy. Only 6 of 17 mucinous ovarian carcinomas were detected. Specificity was 83%. CEA was elevated above 5.0 micrograms/liter in 15 of 17 patients with mucinous ovarian cancer. TPA detected advanced stages of malignancy, but the sensitivity was low, 53%, in cases with limited disease. PLAP was elevated in 46% of ovarian carcinoma patients. For detecting malignancy overall, the use of a parallel combination of the CA-125 and CEA assays was more sensitive than use of CA-125 as a single marker. This test combination may be of value in the diagnosis of adnexal masses. The predictive value of a positive result was 90%, and that of a negative result, 76%.

Unusual primary lung neoplasms: spindle cell and undifferentiated lung carcinomas expressing only vimentin.

Two unusual primary carcinomas of the lung are described. One occurred in a 31-year-old man and was composed of large, undifferentiated, ovoid to polygonal cells. The other occurred in a 72-year-old man, was composed of spindle-shaped cells, and was initially diagnosed as a localized fibrous mesothelioma. The neoplastic cells of these tumors expressed only vimentin intermediate filaments and showed no other immunohistochemical features of epithelial neoplasms, although they exhibited a metastatic pattern characteristic of lung carcinomas. These two malignant neoplasms further expand the spectrum of unusual lung neoplasms, and suggest that there are pulmonary carcinomas that contain only vimentin intermediate filaments.

A high-performance liquid chromatographic method for determination of hypoxanthine in cord plasma.

A reversed-phase high-performance liquid chromatographic method was developed for the analysis of hypoxanthine in cord plasma. Cord plasma was precipitated with ammonium sulphate and after centrifugation the supernatant was injected into the chromatographic system. Separation of hypoxanthine was optimal with phosphate buffer (20 mmol/l, pH 7.65-7.75) as the mobile phase. Limit of determination using 200 microliter of the sample was found to be 1 mumol/l with a coefficient of variation of less than 10%. The imprecision of this method at the 10 mumol/l level was about 2%. The method described in this report for determination of hypoxanthine in cord plasma would also be suitable for determination of hypoxanthine in other biological fluids in clinical investigations. We have also determined reference values for hypoxanthine in citrate-preserved cord plasma. Rigorous sampling conditions and sample handling are important to achieve accurate results.

Resistance against Leishmania donovani induced with an aluminum hydroxide vaccine.

Mice immunized with a subcutaneous protocol combining killed parasites and aluminum hydroxide gel exhibited significant resistance against subsequent challenge with Leishmania donovani promastigotes. Protection was greatest using 25 mg of aluminum hydroxide per injection. Resistance elicited by this killed parasite and aluminum hydroxide protocol was as effective on day 14 as that provided by immunization with a glucan and killed parasite preparation, and more effective in hepatic amastigote reduction at day 28. The effectiveness of aluminum hydroxide as an adjuvant appears to result, at least in part, from its ability to activate macrophages, thus aiding in the elimination of this intracellular parasite.

Autologous red blood cell and platelet engulfment in hairy cell leukemia.

Seven cases of hairy cell leukemia (leukemic reticulo-endotheliosis) are presented in which peripheral blood or splenic hairy cells or both were identified engulfing autologous red blood cells or platelets. In 3 patients, approximately 5-15% of their peripheral blood hairy cells were engulfing red cells and platelets. In 2 patients, intercellular junctions were present between processes of hairy cells and were similar to processes occasionally seen connecting Langerhans cells to each other. Also, parallel tubular arrays were identified in the cytoplasm of hairy cells from 2 other patients. We conclude that autologous red blood cell and platelet engulfment is a common finding in hairy cell leukemia.

Langerhans cells and serum precipitating antibodies against fungal antigens in bronchioloalveolar cell carcinoma: possible association with pulmonary eosinophilic granuloma.

In an ultrastructural study of 37 cases of bronchioloalveolar cell carcinoma (BAC), we identified seven cases (19%) in which Langerhans cells (LC) were closely associated with tumor cells. Serum precipitating antibodies against Aspergillus species and/or thermophilic actinomyces were present in five BAC patients whose tumors contained LC and in six patients whose tumors lacked LC. In a simultaneous study we identified marked atypical bronchiolar and alveolar lining cell hypertrophy and hyperplasma in pulmonary eosinophilic granuloma (PEG). Our data plus current information suggesting that PEG is a form of hypersensitivity pneumonitis support our hypothesis that those cases of BAC in which LC are present may rise in localized or diffuse pulmonary scars caused by PEG.

Melanotic schwannoma. Clinical and ultrastructural studies of three cases with evidence of intracellular melanin synthesis.

Three cases of intradural extramedullary melanotic nerve sheath tumors involving spinal nerves are reported. Clinical, roentgenographic, surgical, gross, histologic, and electron-microscopic findings were remarkably similar. Electron-microscopic study of the three neoplasms showed that the individual cells contained melanin pigment in all stages of maturation; in addition, there was prominent basal lamina, micropinocytotic vesicles, and other ultrastructural features consistent with Schwann cell derivation. The total clinical, operative, and morphologic picutre in these cases suggests that the tumors are true melanotic schwannomas capable of intracellular pigment production. The potential of such tumors for recurrence and metastasis is discussed.

Diffuse interstitial pneumonitis. Clinicopathologic correlations in 20 patients treated with prednisone/azathioprine.

Twenty patients with diffuse interstitial pulmonary disease diagnosed by open lung biopsy received combined prednisone/azathioprine therapy. Twelve patients demonstrated improvement with therapy. Each patient's clinical presentation, roentgenologic features and pathologic findings were correlated with their therapeutic response. Patients with an illness of one year's duration or less had a more favorable response to therapy than patients with a greater than two year duration of illness. Patients with associated extrathoracic abnormalities (anemia, glomerulitis, hepatopathy) exhibited a better therapeutic response that those with only pulmonary disease. The biopsy material from each patient was quantitatively graded on 20 morphologic variables. Statistical analysis using multiple linear regression revealed that a single variable, degree of interstitial fibrosis, was more that 90 per cent accurate in separating those responsive to therapy from those who failed to respond. Patients who respond to treatment had less interstitial fibrosis. Neither the amount of alveolar septal inflammation nor intra-alveolar cellular reaction was discriminatory in predicting response to therapy. A beneficial response to therapy was reflected in both improved lung volumes and gas exchange. Eight patients appeared to have a selective beneficial effect from azathioprine.