Who Shot the Cannonballs? Extensive Lung Metastases in a 39 Year Old Man.

CASE: A 39 year-old man presented to the emergency department complaining of a cough of 2 months in duration. He also complained of weight loss of 20 pounds in two months and night sweats over the same period. An x-ray of the chest was performed and revealed innumerable lung nodules and masses. Computed tomography of the chest and abdomen were subsequently performed which confirmed the masses, but imaging did not reveal an obvious primary source. A testicular exam was performed but no obvious abnormalities were noted. Because of his age as well as the appearance of the lesions, a testicular ultrasound was then performed. The ultrasound found evidence of a 1.5 cm hypoechoic mass on the right testicle with dystrophic calcification in the interpolar region. Urology performed a right radical inguinal orchiectomy. Pathology demonstrated a malignant mixed germ cell tumor with seminoma and yolk sac components being prominent. He underwent four cycles of etoposide, ifosfamide, and cisplatin. His last positron emission tomography scan did not demonstrate active disease. DISCUSSION: Each year about 8700 men are diagnosed with testicular cancer. 75 percent of these occur between the ages of 20 to 44, and the median age of diagnosis is 33. Testicular cancer should be suspected when a young male presents with metastatic disease such as in this case. In this patient, the genital exam was normal due to the small size of the testicular mass, but he had significant metastatic lesions. When cannonball metastases are seen on imaging, germ cell tumors and renal cell carcinoma should be high in the differential diagnosis.

LIFAC ash--strategies for management.

LIFAC is a more recent addition to flue gas desulphurization methods for reducing sulphur emissions during coal combustion for the production of electricity. Ashes from the combustion of a low-sulphur lignite coal using LIFAC technology were used to evaluate different ash management strategies. The ashes, as produced and after treatment by the CERCHAR hydration process, were examined for their disposal characteristics and their utilization potential in concrete. They were also evaluated as underground disposal material using the AWDS process.

Advanced ash management technologies for CFBC ash.

The combustion of high-sulphur coal demands the reduction of sulphur emissions. The sorbent most often used in sulphur capture technology is calcium-based. Ashes from technologies such as circulating fluidized bed combustion (CFBC), therefore, contain high calcium levels. The use and disposal of these ashes poses challenges, because of highly exothermic reactions with water, high-pH leachates, and excessive expansion of solidified materials. This paper looks at the potential of two post-combustion ash treatment processes, CERCHAR hydration and AWDS disposal, in solving these challenges. A high-sulphur coal-derived CFBC ash is examined, after CERCHAR hydration treatment, in conjunction with a conventionally hydrated ash, in a range of chemical, geotechnical and utilization scenarios. The ashes are used to make no-cement and roller-compacted concrete as well as Ash Water Dense Suspensions (AWDS). The solidified mortar paste from no-cement concrete is subjected to an extensive geochemical examination to determine how solidification progresses and strength develops, from a chemical point of view.

Nutritional status: a continuous quality improvement approach.

Intradialytic parenteral nutrition (IDPN) has been used as nutritional repletion in severely malnourished patients with end-stage renal disease (ESRD). This study presents a retrospective look at hemodialysis patients with malnutrition who were followed-up in the process of continuous quality improvement (CQI). The costs of intravenous supplies, hospitalizations, and morbidity are reviewed. The application of continuous quality improvement was used to identify and follow-up malnourished patients. There were significant decreases in number of hospitalizations and days in the hospital.

The stress of Stroop performance: physiological and emotional responses to color-word interference, task pacing, and pacing speed.

Heart rate, frequency of skin conductance responses, and self-reported anxiety were measured during performance of a computer version of the Stroop Color-Word Interference Test, and during a non-conflicting control task involving the color naming of color patches. Stroop and control stimuli were presented individually in order to vary task pacing. Subjects (N = 48) were divided into three groups assigned to self-paced, externally-paced, and fast externally-paced conditions. Performance data revealed that the relative proportion of speed and accuracy reductions which resulted from the Stroop interference varied according to task pacing and pacing speed. Stroop performance was accompanied by heightened HR levels which were sustained throughout the series. State-Anxiety scores increased after both tasks, but only among subjects who completed a large number of trials, i.e. subjects in the self-paced and fast externally-paced groups. Skin conductance responses only varied according to task order and time within series, irrespective of Stroop interference or task pacing. Overall, the results remained in accordance with an effort account of the relationship between attention and cardiac activity. They also provided indications on how the Stroop test may act as an efficient laboratory stressor.

Improving clinical processes: one dialysis facility's experiences.

Northeast Louisiana Dialysis Center implemented continuous quality improvement (CQI) to improve the quality of care delivered to end stage renal disease (ESRD) patients treated by hemodialysis in their facility. The unit chose to address normalization of calcium and phosphorus and parathyroid hormone (PTH), anemia, nutrition, adequacy of dialysis and dialyzer reuse as well as performance benchmarks by the Health Care Financing Administration (HCFA) core indicators. This article presents the results obtained and the methodology used in this improvement effort. The article also presents nine principles the authors believe necessary for a successful CQI program.

The Quality Cup winner: Fletcher Allen Health Care's early extubation team.

Many organizations are looking for ways to reduce the cost and improve the quality of open-heart surgery. Fletcher Allen Health Care in Burlington, Vermont used a total quality management approach to do just that. The result was a dramatic improvement in outcomes. Fletcher Allen won the 1994 USA Today Quality Cup for its efforts.

Human perception of electric fields and ion currents associated with high-voltage DC transmission lines.

The objective of this study was to assess the ability of humans to detect the presence of DC electric field and ion currents. An exposure chamber simulating conditions present in the vicinity of high-voltage DC (HVDC) lines was designed and built for this purpose. In these experiments, the facility was used to expose observers to DC electric fields up to 50 kV/m and ion current densities up to 120 nA/m2. Forty-eight volunteers (25 women and 23 men) between the ages of 18 and 57 years served as observers. Perception of DC fields was examined by using two psychophysical methods: an adaptive staircase procedure and a rating method derived from signal-detection theory. Subjects completed three different series of observations by using each of these methods; one was conducted without ion currents, and the other two involved various combinations of electric fields and ion currents. Overall, subjects were significantly more likely to detect DC fields as the intensity increased. Observers were able to detect the presence of DC fields alone, but only at high intensities; the average threshold was 45 kV/m. Except in the most sensitive individuals, ion current densities up to 60 nA/m2 did not significantly facilitate the detection of DC fields. However, higher ion current densities were associated with a substantial lowering of sensory thresholds in a large majority of observers. Data analysis also revealed large variations in perceptual thresholds among observers. Normative data indicating DC field and ion current intensities that can be detected by 50% of all observers are provided. In addition, for the most sensitive observers, several other detection proportions were derived from the distribution of individual detection capabilities. These data can form the basis for environmental guidelines relating to the design of HVDC lines.

Use of the spiral vein graft as an arterial substitute for secondary access.

A 30-year-old black male with end-stage renal disease of 8 years' duration had undergone 16 prior access operations and was still without an adequate access for dialysis. A spiral saphenous vein graft conduit was constructed from the left saphenous vein and used as a straight arterial conduit graft between the superficial femoral artery at Hunter's canal and the saphenofemoral vein junction in the groin. The spiral vein graft tube was used as the sole means of dialysis for the next consecutive 750 dialysis procedures over nearly 6 years without any complication.

Superiority of the internal jugular over the subclavian access for temporary dialysis.

We studied angiographically the access route 1-27 months after the insertion temporary dialysis catheters in 52 patients: 32 subclavian and 20 internal jugular. The two groups were statistically similar with respect to age, sex and race. The subclavian catheters were left in for a mean of 11.5 days (2-22) while the internal jugular ones were inserted for 15.8 days (5-25; p = 0.0015). One hundred percent of the internal jugular patients were free of any venogram abnormalities in their venous access return. In marked contrast, 50% of the subclavian sites had mild to severe stricutures with 90% having 70-100% occlusion of the subclavian vein. Six patients had bilateral severe strictures. The long-term stricture rate of subclavian catheters in the subclavian vein was unacceptably high compared to the internal jugular route.

Enantiomers of 7-(2,3-epoxypropoxy)actinomycin D as dual-action DNA-acting antitumor agents.

Enantiomeric forms of (+/-)-EPA [racemic 7-(2,3-epoxypropoxy)actinomycin D] have been synthesized; these are (R)-(+)- and (S)-(-)-EPA, which are active against a range of actinomycin resistant and marginally responsive tumors. The R-(+) enantiomer is uniformly superior to the other forms in all the tumor lines tested. These enantiomers act by binding to DNA, both by intercalation and alkylation at the guanine base of DNA. They are superior to actinomycin D in their in vitro activity against mouse leukemias (L1210 and P388/ADR) and mouse melanoma B16. This superior activity is also evident against all the preceding mouse leukemias and against solid tumors B16 and C26 in vivo. In biochemical action, the enantiomers behave similarly and act primarily by inhibiting DNA synthesis in tumor cells; the only difference found was in their preference for sites in DNA bases during alkylation. The R-(+) enantiomer generates an adduct that is believed to be bonded to the N7-site of guanosine; conversely, the S-(-) isomer forms two adducts with DNA that are different from the preceding one by HPLC and are tentatively assigned O6-guanosine-substituted structures on the basis of their UV, CD, and other chemical behaviors.

Measures of leucine aminopeptidase can be used to anticipate UV-induced age-related damage to lens proteins: ascorbate can delay this damage.

This paper focuses on damage to soluble lens proteins during ultraviolet (UV) light exposure and its prevention by ascorbate (Vitamin C). Using 2.3 X 10(-3) W/cm2 UV A and 0.4 X 10(-4) W/cm2 UV B, aminopeptidase inactivation in lens supernatants is significant after 60 min. Protein aggregation and decreases in tryptophan levels, phenomena associated with UV-induced and cataract-related damage, are observed only after longer (6 h) UV exposure. Thus, it would appear that measurements of aminopeptidase activity can be used to anticipate damage to lens structural proteins. Ascorbate (15 mM) added to soluble lens proteins prior to photoirradiation can prevent some of these changes. The data presented suggest plausible relationships between impaired proteolysis and cataract formation.

Axillary artery to iliac vein vascular access using an externally supported prosthetic graft. A new procedure for the recalcitrant secondary access patient.

The axillary artery-iliac vein graft using externally supported PTFE is a viable option for this difficult patient group. It is capable of functioning well for up to 12 months. Most importantly, despite numerous prior access procedures, the axillary artery and iliac vein in each case were amenable to the procedure. Critical technical points include the use of externally splinted PTFE grafts, avoidance of crossing joints, and angling of the graft in the direction of the iliac vein at that anastomosis. The lack of thrombosis or infection to date, coupled with successful dialysis in every patient, suggests that this is one more option that can be used in the difficult secondary access patient.

The eye lens has an active ubiquitin-protein conjugation system.

Using exogenous 125I-ubiquitin, ubiquitin-lens protein conjugation was observed with supernatants of cultured rabbit lens epithelial cells and lens cortex tissue. Conjugation was ATP-dependent with the greatest variety and amount of conjugates larger than 150 kDa. In vivo production of ubiquitin-protein conjugates in cultured rabbit and beef lens epithelial cells and rabbit lens tissues of different developmental age was established using immunological detection. There were limited similarities between conjugates found in youngest as opposed to oldest tissue. Cultured rabbit cells contained 27 pmol/mg free ubiquitin and 18 pmol/mg conjugated ubiquitin. Levels of free ubiquitin in lens tissue epithelium, cortex, and core were 36, 5, and 5 pmol/mg, respectively. There were only 2 pmol/mg conjugated ubiquitin in each of these tissues. Hydrolysis of 125I-ubiquitin was catalyzed by supernatants of cultured lens cells, beef and human lens tissues, and reticulocytes. Degradation was greatest in epithelial tissues, and least in core. This corroborates studies which show that proteolytic capabilities are attenuated in older tissue. Decreased initiation of proteolysis by ubiquitination as well as diminished proteolysis in older lens tissue may be related to the accumulation of damaged proteins in aging lens tissue.

Delay of UV-induced eye lens protein damage in guinea pigs by dietary ascorbate.

Large accumulations of postsynthetically oxidized proteins are observed in the aged and cataractous eye lens. Ascorbate has previously been used to delay photooxidative damage in vitro. The goals of this study were to confirm that dietary ascorbate can be used to enhance lens ascorbate levels and to determine if lenses with enhanced ascorbate can better withstand photooxidative stress in the form of ultraviolet (UV) light exposure. Guinea pigs were placed on high dietary ascorbate (HDA), 50 mg/day, and low dietary ascorbate (LDA), 2 mg/day, for 21 weeks. Lenses from HDA animals were found to contain 3.3 times more ascorbate than LDA animals. Prior to irradiation, SDS-PAGE protein profiles and exopeptidase activity in HDA and LDA lens soluble proteins were indistinguishable. However upon exposure to UV light, more protein damage (e.g., high-molecular-weight aggregates and enhanced loss of exopeptidase activity) was seen in lens preparations from LDA as compared to HDA animals. These results suggest that ascorbate protects lens components against cataract-like and age-related postsynthetic changes in vivo. As in previous tests on lens preparations, attenuated exopeptidase activity was observed before protein aggregation.

Covalent binding of isomeric 7-(2,3-epoxypropoxy)actinomycin D to DNA.

We have examined the ability of 7-(2,3-epoxypropoxy)actinomycin D (EPA) to bind covalently to DNA and to 2'-deoxyribonucleoside 5'-monophosphates in a simple system in vitro. We have observed initially that EPA binds to DNA and deoxymono- and deoxydinucleotides with intercalative or stacking interactions that are characteristic of actinomycin D (AMD). When EPA is incubated (37 degrees C) for a prolonged period (pH 7.4, 6 h) in contact with either DNA or deoxyribonucleotides, it forms covalent adducts. Deoxyguanosine is always the preferred site of reaction by EPA. After enzymatic digestion of EPA-DNA adduct, three deoxyguanosine (EPA-dG) adducts, one major and two minor, were isolated. These adducts are separable from one another and from other deoxyribonucleoside adducts, e.g., EPA-dA and EPA-dC by reverse-phase HPLC. The authentic EPA-dG, EPA-dA, and EPA-dC adducts were synthesized by a chemical reaction of the epoxide in EPA with the deoxyribonucleotides followed by enzymatic dephosphorylation of the products. From the EPA-DNA adduct the EPA-dG adducts accounted for congruent to 2.2% of EPA employed; the remainder of EPA was completely hydrolyzed to an epoxide ring opened diol derivative, DHPA. DHPA binds to DNA by intercalation only and it does not form covalent adducts. Another model analogue of EPA (EPAMDEA) has the same epoxide-substituted chromophore but lacks the peptide lactone functions; it fails to associate with DNA and consequently it shows no covalent binding of its epoxide with DNA. Formation of a noncovalent intercalation complex between EPA and DNA appears to be a prerequisite for the covalent reaction. Presumably because of these dual interactions, EPA demonstrates superior antitumor activities both in human leukemic cells (CCRF-CEM) in vitro and P388 and L1210 cells in mice. The DNA base specific alkylating activity of EPA, which is derived from a combination of the actinomycin D (AMD) structure and the new epoxide function in the molecule of EPA, attributes to EPA a potentially novel pharmacological behavior that is not inherent of AMD.

Tetracyclic chromophoric analogues of actinomycin D: synthesis, structure elucidation and interconvertibility from one form to another, antitumor activity, and structure-activity relationships.

Two different tetracyclic chromophoric analogues of actinomycin D have been synthesized by engaging two chromophoric DNA-binding functions in actinomycin D, i.e., 2-amino and 3-oxo, into either a 1,4-oxazin-2-one or an oxazole ring system. A third analogue has an extra quinone function at C-8 of the oxazole analogue. In all the analogues the chemical integrity of the peptide lactones of the parent antibiotic is kept intact, but their sterochemistry is altered. The analogues are designed as transport-modified prodrug forms of either the tricyclic active analogues of actinomycin D or actinomycin D itself. All analogues exhibit cytotoxicity that is several-fold less potent than AMD; they also have no binding affinity toward extracellular DNA. Nonetheless, the analogues of the first and the third series show improved antitumor activities (P388 leukemia, CDF1 mice). In fact, two of these analogues having a phenyl substituent at the C-3 site of the oxazinone ring or the C-2 position of the 8-oxo-8H-oxazole ring exhibit the highest antitumor effects. Most of the analogues are active over a broader dose range than actinomycin D and are 6- to 16-fold less cytotoxic to human lymphoblastic leukemia (CCFR-CEM) cells in vitro. The analogues with the most pronounced antitumor activity are those that retain most elements in the peptide stereochemistry of actinomycin D and have a quinone function or demonstrate susceptibility of their chromophores to biotransformation.

A gelatin-specific protease from hamster lung-derived cell cultures.

Gelatin-specific protease activity from hamster lung fibroblasts and their culture media is described. The fibroblasts were derived from hamster lung explant cultures. The gelatin-specific protease activity is latent and seen only after dialysis of either cells or media. The enzyme activity shares many properties of previously reported gelatinases. The activity is inhibited by EDTA, cysteine, and dithioerythritol, whereas it is not inhibited by p-chloromecuribenzoate, N-ethyl maleimide, or phenylmethylsulfonyl fluoride. Of all substrates tested, activity was observed only against gelatin and not against other substrates tested. It was inactive toward collagen, elastin, and methemoglobin. This enzyme may have a role in the digestion of collagen that has been previously cleaved by mammalian collagenase.

Studies on the role of the liver and splanchnic tissues in the production of carbohydrate intolerance in uremia.

The potential contribution of the splanchnic tissues to the carbohydrate intolerance of uremia was studied in fasted, partially nephrectomized rats. The livers of sham operated (C) and partially nephrectomized (Nx) rats were perfused with physiologic concentrations of potential gluconeogenic substrates using a nonrecirculating perfusion apparatus. Glucose release was slightly greater in the livers of Nx rats as compared to C rats. The portal vein concentrations of the potential gluconeogenic precursors were not different in the two groups. Moreover, there were no differences in the net hepatic extraction of alanine, glutamine or glutamate between the two groups of rats. There was also no difference in the production of glucose from U14C alanine. The livers of Nx rats, however, demonstrated less net extraction of lactate and released greater concentrations of betahydroxybutyrate. The increased release of glucose by livers of Nx rats may be at least partially due to their greater hepatic glycogen content.