Search

A concise total synthesis of (±)- N -methyldibromoisophakellin, a member of the monomeric pyrrole-aminoimidazole alkaloid family isolated from the marine sponge Stylissa carbica , was achieved via a net [3+2] cycloaddition to install the cyclic guanidine. This ring annulation employs a 2-amido-1,3-aminoallyl cation obtained under oxidative conditions from variously N -substituted guanidines which in one instance led to isolation of a tetracycle bearing a carbinolamine center through subsequent benzylic oxidation. Finally, the serendipitous formation of a unique, related alkenyl guanidine, N -methylugibohlin, achieved via ring opening of cyclic guanidine under acidic conditions suggests that ugibohlin may be an artifact of isolation., Competing Interests: Conflicts of Interest: The authors declare no competing financial interests. Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Purpose: With the current wide adoption of electronic health records (EHRs) by ophthalmologists, there are widespread concerns about the amount of time spent using the EHR. The goal of this study was to examine how the amount of time spent using EHRs as well as related documentation behaviors changed 1 decade after EHR adoption., Design: Single-center cohort study., Participants: Six hundred eighty-five thousand three hundred sixty-one office visits with 70 ophthalmology providers., Methods: We calculated time spent using the EHR associated with each individual office visit using EHR audit logs and determined chart closure times and progress note length from secondary EHR data. We tracked and modeled how these metrics changed from 2006 to 2016 with linear mixed models., Main Outcome Measures: Minutes spent using the EHR associated with an office visit, chart closure time in hours from the office visit check-in time, and progress note length in characters., Results: Median EHR time per office visit in 2006 was 4.2 minutes (interquartile range [IQR], 3.5 minutes), and increased to 6.4 minutes (IQR, 4.5 minutes) in 2016. Median chart closure time was 2.8 hours (IQR, 21.3 hours) in 2006 and decreased to 2.3 hours (IQR, 18.5 hours) in 2016. In 2006, median note length was 1530 characters (IQR, 1435 characters) and increased to 3838 characters (IQR, 2668.3 characters) in 2016. Linear mixed models found EHR time per office visit was 31.9±0.2% (P < 0.001) greater from 2014 through 2016 than from 2006 through 2010, chart closure time was 6.7±0.3 hours (P < 0.001) shorter from 2014 through 2016 versus 2006 through 2010, and note length was 1807.4±6.5 characters (P < 0.001) longer from 2014 through 2016 versus 2006 through 2010., Conclusions: After 1 decade of use, providers spend more time using the EHR for an office visit, generate longer notes, and close the chart faster. These changes are likely to represent increased time and documentation pressure for providers. Electronic health record redesign and new documentation regulations may help to address these issues., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Aim: In this study, we investigated the prognostic significance of the number of examined lymph nodes in node-negative gastric adenocarcinoma (GC)., Patients and Methods: A total of 1194 node-positive and 1030 node-negative GC patients undergoing potentially curative gastrectomy was enrolled in this study. Patients were stratified into 3 groups according to the number of examined lymph nodes: group 1, ≤ 15; group 2, 16-25; group 3, >25., Results: Patients with node-negative GC had significantly favorable survival compared with those with node-positive. Among patients with node-negative T2-T4 disease, the percentage of locoregional relapse was higher in those with <25 examined lymph nodes than in those with ≥ 25 examined lymph nodes. The number of examined lymph nodes affected the overall survival rates for patients with node-negative T2-T4 GC but not for patients with T1 lesions. Tumor size, tumor location, the number of examined lymph nodes, T status, and the presence of perineural invasion were significant prognostic factors as determined by multivariate analysis in node-negative GC., Conclusions: No survival benefit of examining ≥ 15 lymph nodes was noted for patients with node-negative T1 GC. Extensive lymphadenectomy in patients with node-negative T2-T4 lesions in whom the number of examined lymph nodes was >25 had favorable survival., (Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.)

Purpose: Describe qualitative spectral-domain optical coherence tomography (SD-OCT) characteristics of eyes classified as intermediate age-related macular degeneration (nonadvanced AMD) from Age-Related Eye Disease Study 2 (AREDS2) color fundus photography (CFP) grading., Design: Prospective cross-sectional study., Participants: We included 345 AREDS2 participants from 4 study centers and 122 control participants who lack CFP features of intermediate AMD., Methods: Both eyes were imaged with SD-OCT and CFP. The SD-OCT macular volume scans were graded for the presence of 5 retinal, 5 subretinal, and 4 drusen characteristics. In all, 314 AREDS2 participants with ≥1 category-3 AMD eye and all controls each had 1 eye entered into SD-OCT analysis, with 63 eyes regraded to test reproducibility., Main Outcome Measures: We assessed SD-OCT characteristics at baseline., Results: In 98% of AMD eyes, SD-OCT grading of all characteristics was successful, detecting drusen in 99.7%, retinal pigment epithelium (RPE) atrophy/absence in 22.9%, subfoveal geographic atrophy in 2.5%, and fluid in or under the retina in 25.5%. Twenty-eight percent of AMD eyes had characteristics of possible advanced AMD on SD-OCT. Two percent of control eyes had drusen on SD-OCT. Vision loss was not correlated with foveal drusen alone, but with foveal drusen that were associated with other foveal pathology and with overlying focal hyperreflectivity. Focal hyperreflectivity over drusen, drusen cores, and hyper- or hyporeflectivity of drusen were also associated with RPE atrophy., Conclusions: Macular pathologies in AMD can be qualitatively and reproducibly evaluated with SD-OCT, identifying pathologic features that are associated with vision loss, RPE atrophy, and even possibly the presence of advanced AMD not apparent on CFP. Qualitative and detailed SD-OCT analysis can contribute to the anatomic characterization of AMD in clinical studies of vision loss and disease progression., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objectives: To analyse whether a health tax of 10 New Taiwan Dollars (NT$) (US$0.3) imposed on cigarettes in 2009 will help to reduce cigarette consumption, and whether or not the cigarette tax will affect consumption of alcohol, coffee and tea., Study Design: Time series data for consumption and retail prices of tobacco, alcohol, tea and coffee were collected and analysed for the period 1973-2007., Methods: To establish the Central Bureau of Statistics demand function to estimate the overall demand price elasticities of cigarettes, alcohol, tea and coffee, a seemingly unrelated regression analysis was used. The independent variables were annual consumption of cigarettes, alcohol, tea and coffee. The dependent variables were prices of and expenditures on cigarettes, alcohol, tea and coffee., Results: The estimated own-price elasticities for cigarettes and alcohol are close to -0.726. The own-price elasticities for tea and coffee are less than those for cigarettes and alcohol. Hence, it is predicted that the NT$10 health tax on cigarettes will reduce cigarette consumption by a significant 13.19%. Analysis of cross-price elasticity reveals that alcohol is complementary to cigarettes., Conclusions: Taxation is an effective smoking control policy tool that not only helps to reduce consumption of cigarettes, but also reduces consumption of alcoholic beverages., (Copyright 2010 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Aims: The biologic significance of antioxidant enzymes (AOEs) in gastric adenocarcinoma is still unclear. The aims of this study was to investigate the differential expression of AOEs in gastric carcinoma cells and non-cancerous counterparts and the relationship with the various clinicopathologic variables in gastric cancer patients., Methods: Expression status of MnSOD, Cu/ZnSOD, and catalase was evaluated immunohistochemically in 120 paired gastric cancer and adjacent non-cancerous tissue. The tissues were fixed in absolute methanol immediately after surgical resection and immunohistochemistry was performed by microprobe system using tissuemicroarray slides., Results: All AOEs revealed moderate to strong immunoreactivity in the parietal and intestinal metaplastic cells. Stromal cells in both cancer and non-cancerous tissue expressed MnSOD and catalase but Cu/ZnSOD. Immunoreactivity of MnSOD and catalase was increased in gastric carcinoma cells compared to their non-cancerous counterparts and revealed an association with intestinal type adenocarcinomas whereas immunoreactivity of Cu/ZnSOD did not reveal significant difference between cancer and non-cancerous mucosal cells., Conclusions: Expression of MnSOD, Cu/ZnSOD, catalas in gastric cancer cells and non-cancerous counterparts was different and increased MnSOD and possibly catalase may in part be responsible for the increased risk of intestinal type adenocarcinoma of the stomach.

Temperature-sensitive liposomes (TS-liposomes) have been studied for chemotherapeutic purposes to enhance the release of anticancer drugs at tumor sites. In this study, we prepared poly(N-isopropylacrylamide-co-acrylamide) (PNIPAM-AAM) and polyethylene glycol (PEG)-modified TS-liposomes (PETS-liposomes). PETS-liposomes significantly increased in vitro drug release in serum compared with PEG-fixed or PNIPAM-AAM-modified liposomes. Furthermore, incorporation of both PNIPAM-AAM and PEG into PETS-liposomes enhanced the stabilities of liposomes in serum by inhibiting protein adsorption. In addition, to investigate the therapeutic efficacy of doxorubicin (DOX)-loaded PETS-liposomes, the in vivo antitumor activity of liposomes in combination with hyperthermia was evaluated in a B16F10 melanoma tumor-bearing mouse model. PETS-liposomes showed much higher levels of tumor growth inhibition than PEG-fixed or PNIPAM-AAM-modified TS-liposomes. Moreover, the antitumor activity of PETS-liposomes was enhanced significantly when they were administered in combination with hyperthermia. PETS-liposomes were found to be highly efficacious carriers for the in vivo delivery of anticancer drugs, and to have potential anticancer applications in combination with hyperthermia., ((c) 2006 Wiley-Liss, Inc. and the American Pharmacists Association.)

A programmable quantum computer is experimentally demonstrated by nuclear magnetic resonance using one qubit for the program and two qubits for data. A non-separable two-qubit operation is performed in a programmable way to show the successful demonstration. Projective measurements required in the programmable quantum computer are simulated by averaging the results of experiments just like when producing an effective pure state.

The effect of peroxisome proliferator-activated receptor (PPAR)-alpha activators on the liver is well established, but the other effects on muscle and adipose tissue about lipid metabolism and insulin sensitivity are not clear. We investigated whether PPAR-alpha activation affects adiposity of skeletal muscle as well as adipose tissue and improves insulin sensitivity in spontaneous type 2 diabetes model, Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Thirty-three weeks of aged, 20 male OLETF rats were divided into two groups. Control group (n=10) was fed with chow and treatment group (n=10) with chow contained fenofibrate for 7 weeks. At the age of 40 weeks, all rats were examined with MRI, intravenous glucose tolerance test, and then sacrificed for measurement of fat mass and RNA analyses. The total fat (the sum of subcutaneous, mesenteric, epididymal, and retroperitoneal fat pads) measured by dissection was significantly reduced in treatment group. The signal intensity of muscular adiposity was significantly decreased in treatment group. The mRNA levels of FAT/CD36 and mitochondrial carnitine palmitoyltransferase I (M-CPT I) in liver were remarkably increased. Fasting plasma insulin and leptin levels, insulin response after intravenous glucose loading and homeostasis model assessment insulin resistance (HOMA(IR)) index were lowered in treatment group. Fenofibrate increase mitochondrial fatty acid beta-oxidation in liver but not in skeletal muscle and lower the plasma levels of triglyceride and free fatty acid. It might result in reduction of adiposity of truncal adipose tissue and skeletal muscle. We suggest that reduction of adiposity in trunk and skeletal muscle might improve insulin sensitivity.

The rat primary cultured-airway monolayer has been an excellent model for deciphering the ion channel after nystatin permeabilization of its basolateral or apical membrane. Inwardly rectifying K(+) currents were characterized across the basolateral membrane in symmetrical HCO(-)(3)-free high K(+) Ringer's solution (125 mM) in this study. The potency of K(+) channel inhibitors against K(+) conductance was Ba(2+) (IC(50) = 5 microM) > Cs(+) (IC(50) = 2 mM) >> glybenclamide (IC(50) > 5 mM) >> TEA (IC(50) >> 100 mM). The application of basolateral Cs(+) changed K(+) conductance into an oscillating current, and its frequency (holding voltage = -100 mV) increased with increase in concentration of basolateral Cs(+) (0.05-5 mM) and in degree of hyperpolarization. Addition of basolateral Cs(+) blocked inward current strongly at -100 mV and hardly at all at -60 mV, giving a sharp curvature to the I-V relation of the IRK current. RT-PCR, Western blotting, and immunohistochemical analyses showed that Kir2.1 might be present in basolateral membrane of tracheal epithelia and plasma membrane of pulmonary alveolar cells., (Copyright 2001 Academic Press.)

In the present study we have examined the effect of DCDC (2',5'-dihydroxy-4-chloro-dihydrochalcone) on lipopolysaccharide (LPS)-induced responses in murine macrophage cell line RAW 264.7. Exposure of LPS-stimulated cells to DCDC inhibited the nitrite accumulation in culture medium. DCDC also concentration-dependently inhibited LPS-stimulated increase of iNOS expression; however, it had little effect on iNOS enzyme activity, suggesting that the inhibitory action to DCDC is mainly due to the inhibition on iNOS expression rather than iNOS enzyme activity. DCDC significantly inhibited LPS-evoked degradation of IkappaB-alpha and the nuclear translocation of NF-kappaB; it also exhibited the activity of scavenging the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH). DCDC also inhibited cyclooxygenase-2 activity in RAW 264.7 cells with an IC50 of 3.0 microM; furthermore, it also significantly decreased LPS-induced mortality rate in mice. Taken together, we demonstrate that DCDC exhibits inhibitory effects on nitric oxide production through the inhibition of IkappaB-alpha degradation and NF-kappaB activation, and therefore the suppression of iNOS expression. DCDC also shows the antioxidant activity and COX-2 inhibitory action. Moreover, it improves survival in a murine model of endotoxaemia suggesting that DCDC may be potential in the therapy of septic shock.

The D-amino acid oxidase cDNA gene (daao) of Trigonopsis variabilis was prepared by reverse transcriptase-polymerase chain reaction (PCR) and cloned into Escherichia coli expression vector, pTrc99A, under the control of tac promoter. Expression of daao gene significantly affected the growth and morphology of E. coli. The highest D-amino acid oxidase (DAAO) activity was 705 U (mg of protein)(-)(1), which was about 12-fold higher than that of D-alanine-induced T. variabilis. The DAAO protein exhibited activity on native-PAGE and had a M(r)value of 39.3 kDa. We also constructed an expression plasmid, pKm-DAAO, in which kanamycin instead of ampicillin was used as the selective marker. High-performance liquid chromatography (HPLC) analysis demonstrated that cephalosporin C could be converted to 7-glutarylcephalosporanic acid by cell-free extract of E. coli harboring pKm-DAAO. Four inactive DAAO mutants were obtained by error-prone PCR. Sequence analysis of these four DAAO mutants indicated the occurrence of mutations at Val-167, Pro-291, Pro-309, and Ala-343 residues. The His(6)-tagged DAAOs were expressed in E. coli and purified by nickel ion affinity chromatography. The results showed that all DAAO mutants lost their enzymatic activities and characteristic adsorption spectra for flavoenzyme. Based on the crystal structure of a homologous protein, pig DAAO, it is suggested that these four residues may play essential structural roles in DAAO conformation, thereby influencing DAAO's catalytic activity.

Many types of NMR experiments demand the use of frequency-selective pulses to invert magnetization within discrete frequency limits. For certain experiments, only one side of the inversion band must be sharply demarcated, in which case this transition bandwidth can be narrowed when using an asymmetric adiabatic full passage. In the present study, a highly efficient asymmetric adiabatic full passage was created from a combination of two adiabatic half passages which used different modulation functions (HS12 and tanh/tan). Each adiabatic half passage occupied a different amount of time in the total pulse and performed one-half of the inversion. On one side, HS12 produced a sharp transition between inverted and noninverted states which was approximately 2.5 times narrower than the transition bandwidth afforded by a symmetric hyperbolic secant pulse of equal length. On the other side of the narrow transition band, the tanh/tan pulse achieved broadband inversion. These asymmetric pulses were applied to select NH groups immediately adjacent to the water signal in water-flip-back HSQC experiments using a double spin echo for the reverse INEPT step., (Copyright 1999 Academic Press.)

Background: Reconstruction of the esophagus for complicated benign stricture or after resection of malignant lesion is still a challenge for surgeons. When abdominal viscera cannot be used, skin flaps are selected for esophageal reconstruction. However, skin flaps for esophageal reconstruction are notorious for leakage, and have not been widely accepted. Prefabrication before microvascular transfer to its final site can improve the result of esophageal reconstruction when skin flaps are used., Methods: Eight patients with complicated corrosive esophagitis had been treated with prefabricated skin flaps for esophageal reconstruction. The procedures are described in detail., Results: All patients healed well without leakage. The barium study showed smooth passage. There was no dysphasia or regurgitation after education. Pulmonary complication happened in only 1 patient. Revision for the distal anastomosis was required in 1 patient due to narrowing. When the skin tube is long, the patients need water (or soup) to facilitate swallowing and occasionally use their hand to help the food passage. This method has the following advantages: (1) healing of the long suture line before transfer to withstand the intestinal juice; (2) reliable viability in the distal part of the flap, especially when an extended length of the flap is required; (3) more length of stable tissue for two-layered, tension-free anastomosis at the junction of skin and gastrointestinal mucosa to prevent leakage; and (4) the flap can be placed in the substernal position to meet the aesthetic requirement of young patients. The disadvantage was the staged operations. However, after prefabrication the transfer becomes safe and free of leakage. The overall morbidity is minimal., Conclusions: In rare situations when skin flaps are used for esophageal reconstruction, prefabrication provides advantages over conventional one-stage methods, although it needs additional procedures. This method is a combination of conventional technique and microsurgery.

Rotating-frame NMR experiments which either emphasize or suppress cross relaxation, and which simultaneously suppress TOCSY, COSY, and zero-quantum peaks in NMR spectra, are presented and analyzed. The new experiments rely on mixing sequences which follow naturally from the transverse-ROESY (Tr-ROESY) sequence of Hwang and Shaka, and which are applicable to larger molecules in solution (spin diffusion limit). In the first variant a modified Tr-ROESY sequence, called multiple-pulse ROESY (MP-ROESY), is used to enhance cross-relaxation peak intensity compared to Tr-ROESY; in the second, called phase-modulated CLEAN chemical exchange (CLEANEX-PM), cross-relaxation peaks are greatly attenuated. The two methods are thus complementary: MP-ROESY is used to observe Overhauser peaks, and CLEANEX-PM is used to eliminate them, permitting clear observation of chemical exchange peaks alone. The new techniques are examined by theory and experiment. Practical guidelines that will result in high-quality spectra are given, including the judicious use of continuous weak static magnetic field gradients., (Copyright 1998 Academic Press.)

Despite the advantages of compensation for resonance offset and B1 inhomogeneity, adiabatic pulses are not yet in general use in high-resolution NMR, often because of the conception that these pulses require longer time or increased power to perform. We show that adiabatic pulses with tangential frequency sweeps and other frequency-modulation functions can be optimized to accomplish 13C and 1H broadband inversion using pulse lengths of 192 and 64 micro(s), respectively, at B1 strengths available with modern high-resolution probes., (Copyright 1998 Academic Press.)

Purpose: To study the relation between vascular patterns and the biologically aggressive behavior of ciliary body melanomas., Methods: The authors compared the frequency distribution of vascular patterns by location for 234 uveal melanomas (54 tumors involving the ciliary body, and 180 without ciliary body involvement). Stepwise Cox regressions (for the endpoint of time-to-death due to melanoma), performed separately for melanomas with and without ciliary body involvement, included the following variables: size, vascular patterns, cell type, mean of the largest nucleoli, mitoses, tumor infiltrating lymphocytes, age, and sex. A separate Cox regression procedure included the variable of tumor location. Kaplan-Meier survival curves were generated for time to melanoma death with ciliary body involvement and melanomas without ciliary body involvement for tumors containing or lacking vascular networks., Results: These vascular patterns appear more often in the ciliary body than in the choroid: parallel vessels (P = 0.022), arcs (P = 0.003), and parallel with cross-linking, arcs with branching, and loops and networks (all P = 0.0001). Stepwise regression for tumors confined to the choroid indicated that the presence of networks was the most significant variable (P = 0.0001); stepwise regression for tumors with ciliary body involvement suggested that only one variable, networks, was significant (P = 0.0066). Kaplan-Meier survival estimates indicated that the survival of patients with tumors containing networks in the ciliary body was comparable to those containing networks in the choroid., Conclusion: Regardless of location, ciliary body or choroid, the presence of vascular networks shortens survival. The tumor location does not enter a stepwise Cox regression model when vascular patterns are included as variables. Therefore, the aggressive behavior of ciliary body melanomas appears to be related to the tendency for vascular networks to develop in this location.

Background: Cytomorphometric measurements and the architecture of the microcirculation in tissue sections of eyes removed for ciliary body or choroidal melanomas have been identified independently as prognostically significant factors for survival. The relative significance of these two histologic features is addressed in this study., Methods: The same 234 cases used to assess the prognostic significance of the microcirculatory patterns of choroidal and ciliary body melanomas were examined by two independent observers who measured the largest diameter of melanoma cell nucleoli from digitized images at a high magnification (x 3000) using the laser scanning confocal microscope. The mean of the ten largest nucleoli was calculated for each tumor according to previously published methods. Intraobserver and interobserver reproducibility was assessed for these measurements. Several Cox multiple regression models were constructed which included this cytomorphometric variable with and without the inclusion of the microcirculatory patterns., Results: There is a high degree of intraobserver reproducibility but only a weak degree of interobserver reproducibility in measuring the mean of the ten largest nucleoli. Using multiple Cox regression models, the mean of the ten largest nucleoli from each observer failed to exert any effect on outcome after enucleation, regardless of whether the presence of networks of closed vascular loops was considered in the statistical formulation. The presence of networks of closed vascular loops was found to be the most statistically dominant histologic prognostic characteristic., Conclusion: The authors have not been able to confirm the use of the mean of the ten largest nucleoli as a significant prognostic factor in the outcome of patients whose eyes have been removed for ciliary body or choroidal melanomas. Further investigation of this cytomorphometric technique by other laboratories is warranted.

Purpose: This study was designed to (1) describe the vascular patterns of ciliary body and choroidal nevi by light microscopy, (2) compare the vascular ultrastructure of nevi with vessels of the normal uvea and uveal melanomas, and (3) compare the behavior of ciliochoroidal melanomas with and without a nevus-like vascular architecture., Methods: After delineating the vascular patterns of 23 choroidal and ciliary body nevi by light microscopy, the authors identified 49 melanomas that had the same vascular patterns as nevi from a previously published series of 234 uveal melanomas. The survival of these 49 patients who had melanomas with a nevus-like vascular architecture was compared with the 185 patients who had melanomas that lacked this vascular profile., Results: By light microscopy, the only vascular patterns identified in nevi are "normal" vessels, zones of avascularity ("silent" pattern), straight, and parallel vessels; closed vascular loops and networks were not detected in nevi. By transmission electron microscopy, the vascular basement membrane of malignant melanomas was multilaminar, fragmented, and significantly thicker than in normal eyes or nevi. None of the patients with nevi died of metastatic disease. Fourteen percent of patients whose melanomas had the same vascular profile as nevi died of metastatic disease, whereas 32% of patients whose melanomas had vascular patterns other than those seen in nevi died of metastatic melanoma (P = 0.012)., Conclusions: The microcirculation architecture marks tumor progression in uveal melanocytic lesions by light and electron microscopy. In the spectrum of these lesions, nevi are benign, melanomas that have the same vascular profile as nevi have an intermediate biologic behavior, and melanomas with vascular networks are strongly associated with death due to metastatic disease.

Background: It is possible to identify at least nine vascular patterns in melanomas of the ciliary body and choroid from histologic sections. An association between the presence of at least one closed vascular loop and death from metastases was shown in a matched-pair, case-control study of 40 patients whose eyes were removed for ciliary body or choroidal melanomas., Methods: Two independent observers who were masked to the follow-up of patients examined histologic preparations of 234 eyes removed for ciliary body or choroidal melanomas for the presence of each of the tumor vascular patterns. Statistical analyses included tests for interobserver reliability, Kaplan-Meier survival curves, and the fitting of Cox regression models., Results: The detection of each of the nine vascular patterns is highly reproducible. The Cox model indicates that the presence of vascular networks, defined as at least three back-to-back closed vascular loops, is the feature most strongly associated with death from metastatic melanoma. Other significant factors in the Cox model include (in descending order of importance) largest tumor dimension, mitoses, the parallel with cross-linking vascular pattern, age, the presence of tumor-infiltrating lymphocytes, and male gender., Conclusions: The presence of vascular networks provides the most significant association with death from metastatic melanoma of all variables tested. The presence of this pattern should be recorded on pathology reports. If it becomes possible to detect this vascular pattern clinically using a noninvasive imaging technique, then ophthalmologists may be able to determine the likely biologic behavior of a melanoma before resorting to the removal of tissue.

A rare case of spinal intramedullary granulocytic sarcoma (GS) in a patient with acute myelogenous leukemia is described along with its magnetic resonance (MR) finding. The mass shows isointense signal on T1-weighted images, and slightly higher intensity on T2-weighted images. Contrast enhancement with gadolinium (Gd)-DTPA in this case differs from the other report in which the tumor was not enhanced. As MRI becomes the first choice in the evaluation of spinal tumors, high index of suspicion of GS with familiarity with its MR finding in leukemic patients may obviate the need for surgical intervention, since the tumor is sensitive to both radiation and chemotherapy.

The effects of intravenous fat emulsion on ventilated normal, diseased or distressed lungs were studied. Forty-eight patients with different types of respiratory failure were divided into four groups. Group A was composed of the patients with a normal lung condition; group B, patients with infectious pulmonary condition and respiratory failure; group C, patients with COPD and respiratory failure; and, group D was composed of the patients with ARDS due to various causes. Five hundred milliliters of 10 percent fat emulsion was infused within 4 h as partial parenteral nutritional support. We concluded that intravenous fat infusion decreased PaO2/FIO2 and increased P(A-a)O2 and intrapulmonary shunt in the patients with ARDS, while it had little effect on the patients with infectious pulmonary disease or COPD. The infusion of fat emulsion had positive effects on the patients with normal lung condition with increased PaO2/FIO2 and decreased P(A-a)O2 and shunt.

Tumor cells obtained from leukemia and lymphoma patients were investigated for specific insulin receptors. Using radioactive 125I-labeled insulin, specific insulin binding sites were demonstrated on most acute lymphocytic leukemia (ALL) and acute myelocytic leukemia (AML) cells, including acute promyelocytic leukemia (APL), chronic myelocytic leukemia (CML), and acute monocytic leukemia (AMoL) cells. Insulin receptors were not found on chronic lymphocytic leukemia (CLL) and malignant lymphoma (ML) cells. Specific insulin binding sites were also found on monocytes and thymocytes after treatment with phytohemagglutinin (PHA-P), but not on inactivated tonsil cells, peripheral blood lymphocytes, or thymocytes. There was no inverse correlation between the content of insulin receptors and the basal level of circulating insulin. These data suggest that the insulin receptor may be a new marker of acute leukemia and chronic myelocytic leukemia.

The possibility that hypercalciuria could cause calcium stone formation through a mechanism other than by increasing urinary saturation of stone-forming calcium salts was explored. The effect of increasing calcium concentration on the inhibitor activity against the spontaneous precipitation of calcium oxalate was examined in whole urine (in the presence of naturally occurring inhibitors) and in synthetic media (with added inhibitors). In 11 patients with calcium nephrolithiasis, the induced hypercalciuria from calcium supplementation (600 mg/day) caused a significant fall in the urinary inhibitory activity against calcium oxalate precipitation, as shown by a decline in the formation product ratio from 12.6 +/- 1.1 SEM to 9.6 +/- 1.4 (P less than 0.005). In order to more fully explore this observation, the effect of increasing calcium concentration on the inhibitory activities of citrate (2 mM), chondroitin sulfate (0.05 mg/liter) and a heterogeneous group of naturally-occurring urinary inhibitors (1.0 mg/liter) against calcium oxalate precipitation was examined in vitro in synthetic solutions. The inhibitory actions of both citrate and chondroitin sulfate were significantly attenuated by increasing calcium concentration from 0.25 mM to 6.0 mM (P less than 0.01). However, raising the calcium concentration in synthetic media containing a mixture of partially purified urinary inhibitors produced a significant rise in the urinary inhibitory activity of this macromolecular mixture (P less than 0.01). We conclude that hypercalciuria can attenuate the inhibitory activities of citrate and chondroitin sulfate against calcium oxalate precipitation while at the same time accentuating the inhibitory activity of naturally-occurring urinary inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)