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Objective: RNase L is converted to an active form upon binding short 2',5'-oligoadenylates (2-5A). To direct RNase L to an RNA target, 2-5A is attached to an antisense oligonucleotide (2-5A antisense). This chimera can be directed against telomerase-an RNA-protein complex that elongates telomeric DNA and is involved in cellular immortalization. Our objective is to investigate the effect of 2-5A antisense by targeting telomerase RNA (hTR) in the ovarian cancer cell line, HEY-1B., Methods: Baseline RNase L levels and telomerase activities were measured in both HEY-1B and normal ovarian epithelial cells (NOE). Cells were treated daily with chimeric oligonuclotides (ODN) directed against four different hTR sites, or control ODNs including nonchimeric antisense, 2-5A fused to a mismatched sequence, or inactive 2-5A fused to antisense. At 48 h, apoptosis was evaluated using the TUNEL assay. After six daily ODN administrations, telomerase activity was redetermined, and at 7 days viability counts were obtained., Results: Both cell lines expressed similar levels of RNase L. Hey-1B displayed telomerase activity while NOE did not. After 7 days of transfection, 2-5A antisense ODNs caused profound cell death in the HEY-1B cells, but not in the NOE cells. This effect was seen regardless of hTR target site, and ODN controls showed no significant decrease in cell viability in either cell line. HEY1B cells treated with 2-5A antisense against hTR showed a decrease in telomerase activity and a profound induction of programmed cell death., Conclusions: The results suggest that 2-5A antisense directed against telomerase RNA results in apoptotic cell death in ovarian cancer cells, but not normal ovarian epithelial cells. The 2-5A antisense strategy may hold a considerable advantage over the conventional antisense approach in targeting cancer-causing genes., (Copyright 2000 Academic Press.)

Over the last few years, antisense technology has emerged as an exciting and promising strategy in the fight against cancer. The antisense concept is to selectively bind short, modified DNA or RNA molecules to messenger RNA in cells and prevent the synthesis of the encoded protein. As anticancer agents, these molecules can be targeted against a myriad of genes involved in cell transformation, cell survival, metastasis, and angiogenesis. Indeed, the list of possible antisense targets increases as the knowledge of the genetic basis of oncogenesis expands. One aim of this review is to focus on those antisense cancer drugs that have entered human clinical trials. At least four of these compounds are currently in phase II trials, including those targeting protein kinase C-alpha, bcl-2, c-raf, and the R1-alpha subunit of protein kinase A. A new development in antisense chemistry (peptide nucleic acids) is discussed, along with alternative antisense-related strategies (ribozymes and 2-5A-antisense) designed to overcome some of the challenges of this already encouraging technology.

Reduced cell surface levels of major histocompatibility complex class I antigens enable adenovirus type 12 (Ad12)-transformed cells to escape immunosurveillance by cytotoxic T lymphocytes (CTL), contributing to their tumorigenic potential. In contrast, nontumorigenic Ad5-transformed cells harbor significant cell surface levels of class I antigens and are susceptible to CTL lysis. Ad12 E1A mediates down-regulation of class I transcription by increasing COUP-TF repressor binding and decreasing NF-kappaB activator binding to the class I enhancer. The mechanism underlying the decreased binding of nuclear NF-kappaB in Ad12-transformed cells was investigated. Electrophoretic mobility shift assay analysis of hybrid NF-kappaB dimers reconstituted from denatured and renatured p50 and p65 subunits from Ad12- and Ad5-transformed cell nuclear extracts demonstrated that p50, and not p65, is responsible for the decreased ability of NF-kappaB to bind to DNA in Ad12-transformed cells. Hypophosphorylation of p50 was found to correlate with restricted binding of NF-kappaB to DNA in Ad12-transformed cells. The importance of phosphorylation of p50 for NF-kappaB binding was further demonstrated by showing that an NF-kappaB dimer composed of p65 and alkaline phosphatase-treated p50 from Ad5-transformed cell nuclear extracts could not bind to DNA. These results suggest that phosphorylation of p50 is a key step in the nuclear regulation of NF-kappaB in adenovirus-transformed cells.

Since the discovery of D20 (heavy water) and its use as a moderator in nuclear reactors, its biological effects have been extensively, although seldom deeply, studied. This article reviews these effects on whole animals, animal cells, and microorganisms. Both "solvent isotope effects," those due to the special properties of D20 as a solvent, and "deuterium isotope effects" (DIE), which result when D replaces H in many biological molecules, are considered. The low toxicity of D20 toward mammals is reflected in its widespread use for measuring water spaces in humans and other animals. Higher concentrations (usually >20% of body weight) can be toxic to animals and animal cells. Effects on the nervous system and the liver and on formation of different blood cells have been noted. At the cellular level, D20 may affect mitosis and membrane function. Protozoa are able to withstand up to 70% D20. Algae and bacteria can adapt to grow in 100% D2O and can serve as sources of a large number of deuterated molecules. D2O increases heat stability of macromolecules but may decrease cellular heat stability, possibly as a result of inhibition of chaperonin formation. High D2O concentrations can reduce salt- and ethanol-induced hypertension in rats and protect mice from gamma irradation. Such concentrations are also used in boron neutron capture therapy to increase neutron penetration to boron compounds bound to malignant cells. D2O is more toxic to malignant than normal animal cells, but at concentrations too high for regular therapeutic use. D2O and deuterated drugs are widely used in studies of metabolism of drugs and toxic substances in humans and other animals. The deuterated forms of drugs often have different actions than the protonated forms. Some deuterated drugs show different transport processes. Most are more resistant to metabolic changes, especially those changes mediated by cytochrome P450 systems. Deuteration may also change the pathway of drug metabolism (metabolic switching). Changed metabolism may lead to increased duration of action and lower toxicity. It may also lead to lower activity, if the drug is normally changed to the active form in vivo. Deuteration can also lower the genotoxicity of the anticancer drug tamoxifen and other compounds. Deuteration increases effectiveness of long-chain fatty acids and fluoro-D-phenylalanine by preventing their breakdown by target microorganisms. A few deuterated antibiotics have been prepared, and their antimicrobial activity was found to be little changed. Their action on resistant bacteria has not been studied, but there is no reason to believe that they would be more effective against such bacteria. Insect resistance to insecticides is very often due to insecticide destruction through the cytochrome P450 system. Deuterated insecticides might well be more effective against resistant insects, but this potentially valuable possibility has not yet been studied.

Mild traumatic brain injury is misleading as a diagnostic term, as it may include a spectrum of manifestations ranging from transient mild symptoms to ongoing disabling problems. It is a source of significant economic burden to society in terms of days lost from work and costs related to medical treatment. Symptomatic individuals will frequently present to primary care general medical practitioners days, weeks, or even months after the trauma. General medical practitioners are thus put in the position of being the "gatekeepers" of medical care for such patients and become responsible for appropriate determination and authorization of medical tests, specialized referrals, and treatment. The purpose of this article, which is based on a review of the literature to 1997, is to provide physicians with an understanding of mild traumatic brain injury, including manifestations and treatment, as it occurs commonly and can significantly impact the quality of life of those affected.

Objective: Our objective was to determine the level and timing of peak hepatic enhancement in children using power injection of contrast media, helical CT, and computer-automated scan technology., Subjects and Methods: Forty-nine abdominal CT studies were performed using computer-automated scan technology. Patients were divided into four groups on the basis of body weight and contrast dose (group 1A, < or = 20 kg and 2 ml/kg; group 1B, < or = 20 kg and 3 ml/kg; group 2, 21-40 kg and 2 ml/kg; group 3, > 40 kg and < or = 2 ml/kg). Contrast injection rates were based on body weight (groups 1A and 1B, 1 ml/sec; group 2, 1.5 ml/sec; and group 3, 2 ml/sec). The peak hepatic enhancement level in Hounsfield units and the time to reach peak enhancement were determined for each patient., Results: The mean peak hepatic enhancement and time to peak enhancement after completion of contrast injection were group 1A, 45 H and 11 sec; group 1B, 62 H and 3 sec; group 2, 52 H and 12 sec; and group 3, 45 H and 10 sec., Conclusion: The level and timing of peak hepatic enhancement in pediatric patients can be obtained using computer-automated scan technology. These data may then be used to optimize hepatic enhancement when obtaining helical abdominal CT scans of pediatric patients.

A case of papillary serous ovarian adenocarcinoma with choroidal metastasis to the eye is reported. Central nervous system metastasis of any kind is rare from this tumor, and only three cases of choroidal metastases have been reported to date. A 67-year-old women presented 2 years after diagnosis of Stage IIIC papillary serous ovarian adenocarcinoma with complaints of a "teardrop"-shaped visual field defect in her right eye. Fundoscopic examination revealed metastasis to the superior-temporal right choroid. No coexisting sites of recurrence were discovered. This case highlights the need to thoroughly and promptly investigate the etiology of visual field complaints in patients with a history of ovarian cancer.

A rare case of scalp metastasis from endometrial adenocarcinoma, demonstrating the poor prognosis for these patients, is reported. A 56-year-old woman with FIGO Stage IC, Grade 1 endometrial adenocarcinoma presented 15 months after initial surgery and radiation therapy with a scalp metastasis. Metastatic evaluation revealed widespread extrapelvic disease. She did not respond to chemotherapy and died 3 months after recurrence. Her course typifies that of patients with other cutaneous metastases as described in the literature: disease noted elsewhere at the time of recurrence, poor response to therapy, and death within 6 months.

The purpose of this study is to develop a mathematical model and calculate photon-absorbed fractions in a homogeneous nonradioactive cylinder placed inside off-center and outside a cylindrical homogeneous distribution of activity. In the second case, both the radioactive cylinder and the nonradioactive one are placed in a tissue-equivalent nonradioactive medium. The values of the photon-absorbed fractions are investigated for various geometrical configurations using water as the material filling the cylinders and the medium in between and an isotope commonly used in Nuclear Medicine, 99mTc. The calculations for off-center cylinders allows for modeling inhomogeneous distributions of activity within a tumor by placing several "cold" cylinders of various sizes in a radioactive finite cylinder. This three-dimensional model calculates photon-absorbed fractions for inhomogeneous activity distributions that can be used in quantitative nuclear medicine for self-absorption correction, thus introducing a more realistic correction than the one-dimensional corrections. These calculations are also used to model the response of a cylindrical TLD (thermoluminiscent dosimeter) placed inside a homogeneous radioactive cylinder and outside the homogeneous radioactive cylinder, in an absorbing nonradioactive surrounding medium. The purpose of these calculations is to evaluate the photon-absorbed fraction in the TLD as an instrument of measuring the time-integrated activity of a homogeneous radioactive source versus an inhomogeneous one. The dependence of the TLD-absorbed fraction on the position of the TLD with respect to the radioactive cylinder is investigated.

The purpose of this study was to calculate photon absorbed fractions in tissue surrounding a radioactive source where both the source and the surrounding tissue are assumed to have cylindrical geometry. Specifically, we treated two cases: the case of a cylindrical source of homogeneous activity placed in air, and second, the case of a cylindrical source of homogeneous activity placed in a cylindrical nonradioactive absorbing material. In this study we offer an analytical solution to these problems followed by numerical integration. The computer program allowed for very general calculations, e.g., different tissues, different geometrical setups. Tables of absorbed fractions have been developed for commonly used radionuclide energies and tissue-equivalent material. A comparison between our results and the results of other related studies showed the advantages and limitations of this approach.

Cell extracts from knockout mice can provide definitive proof of antibody specificity. Two NF-kappa B1-p50 antibodies, sc-114 (a commercial antibody) and NR1157, were observed to recognize proteins having distinct electrophoretic mobilities of 52-55 kD and 50 kD, respectively, by Western blot analysis. In order to discriminate the specificity of these antibodies for NF-kappa B1-p50, whole cell extracts derived from NF-kappa B1-p105 knockout mice were employed. While the NR1157 antibody completely failed to recognize its 50 kD product in p105-/- knockout extracts, the sc-114 antibody still strongly recognized its 52-55 kD product. These data demonstrate that NR1157, but not sc-114, is highly specific for NF-kappa B1-p50 by Western blot analysis. In addition, these results highlight the utility of knockout cell extracts for discerning antibody specificity.

Persons with acquired immune deficiency syndrome (AIDS) are subject to a host of pathologic entities secondary to a depressed immune system. Kaposi's sarcoma frequently presents in this immunocompromised population and, therefore, diagnosis seems clinically straightforward. However, because of the prevalence of a strikingly similar infectious disease known as bacillary angiomatosis, skin biopsy of one or more lesions is crucial.

Hand-foot-and-mouth disease is a highly contagious disease most often seen in children during the summer. It is caused most commonly by the virus coxsackie A16, but other enteroviruses have been implicated. It presents with low grade fever, and a vesicular eruption on the hands, feet, and mouth. More serious manifestations are seen less commonly. Diagnosis is most often clinical and treatment is symptomatic in nature. The infection in a male adult is presented.

The major histocompatibility complex class I enhancer is the target for adenovirus-12 E1A-mediated down-regulation of class I transcription. In Ad12 transformed rodent cells, the class I enhancer is down-regulated through increased binding of the repressor COUP-TF to the R2 element and decreased binding of the activator NF-kappa B (p50/p65) to the R1 element. The reduced surface levels of class I antigens contribute to the tumorigenic potential of Ad12 transformed cells by favoring their immunoescape from cytotoxic T-lymphocytes. Previous studies using transformed cells containing hybrid Ad5/Ad12 E1A (plus Ad12 E1B) genes have indicated that sequences within the first exon of the 266R Ad12 E1A gene are required for class I down-regulation and tumorigenesis. In this study we demonstrate that these same sequences, which exclude the Ad12 CR3 transactivation domain, are also required for increased COUP-TF binding to the R2 element and decreased NF-kappa B binding to the R1 element of the class I enhancer. We further show that diminished NF-kappa B binding is not due to a lack of NF-kappa B1-p50 in the nuclei of Ad12 transformed rat cells.

Nickel (Ni) toxicity to growth and photosynthesis was studied in four strains of Scenedesmus acutus f. alternans. Effects of Ni dosage and duration of exposure on growth and photosynthesis were strain specific. Large differences in responses of both growth and photosynthesis to Ni were detected between three resistant strains (B4, Cu-Tol, and Ni-Tol) and one sensitive strain (UTEX 72). Growth of UTEX 72 was ≥ 18 times more sensitive to Ni than those of the three resistant strains. The order of Ni dosages (fmol Ni/pg cell dry weight) causing 50% inhibition (D150) of growth rates in the four strains was Ni-Tol (10.5) > B4 (8.19) > Cu-Tol (4.60) > UTEX 72 (0.25). The effect of Ni dosage on photosynthetic rate as percentage of control corresponded to a saturation curve and was a strong function of duration of exposure. The DI50s of photosynthetic rates were ≥3.5 times lower in UTEX 72 than in the three resistant strains, and in all four strains they decreased sharply with the increase in duration of exposure. The order of the four strains in DI50s of photosynthetic rate was B4 (58.2) > Cu-Tol (38.0) > Ni-Tol (28.9) > UTEX 72 (8.24) for 6-h exposure and Ni-Tol (2.88) > Cu-Tol (1.30) > B4 (1.01) > UTEX 72 (0.15) for 24-h exposure. The DI50s of photosynthetic rate for 6-h exposure were higher than those of growth rate in all four strains, and for 24-h exposure they were lower, except in UTEX 72. Thus, the relative Ni sensitivity of growth and photosynthesis of the four strains depends on the duration of exposure. The results of factorial analysis of variance suggested that Ni toxicity to photosynthesis is a consequence of a strong interaction among strain, Ni dosage, and duration of exposure.

Six well-known strains of halotolerant bacteria, including two strains previously identified only as NRCC 41227 and Ba1, have been compared using 125 phenotypic characters and DNA-DNA hybridization. Although these strains represent some of the most heavily studied salt-tolerant bacteria, they have never been taxonomically compared. The data presented show that these bacteria form a relatively homogeneous group related at the genus level. The taxonomic comparison showed that these six organisms represented four distinct species all related above the 65% Jaccard coefficient level. In addition to two previously identified bacterial species, Halomonas elongata (ATCC 33173T) and Halomonas halodurans (ATCC 29686T), the strains included in this study represent two previously unnamed Halomonas species. These two new taxa have been assigned the names Halomonas israelensis (ATCC 43985T) and Halomonas canadensis (NRCC 41227T = ATCC 43984). DNA-DNA hybridization show that these two species are related to the type species H. elongata at 54.9 and 48.9%, respectively.

The history of total hip replacement including that of the Girdlestone procedure and resurfacing procedures is discussed. An overview of total hip replacement and its indications and complications forms the bulk of this section. Also, the use of porous-coated prostheses and endoprostheses as well as pins and plates is discussed and illustrated.

The expression of the larvicidal Bacillus thuringiensis subsp. israelensis cryIVB gene in cyanobacteria has been suggested to be an effective means of controlling mosquito populations. Using a variety of cryIVB constructs, in this study we have examined the effect of Synechococcus PCC 7942 culture age on intracellular toxin levels and have attempted to determine the mechanisms by which cryIVB gene expression is regulated. The data suggest that specific degradation of the cryIVB mRNA limits toxin production; however, the addition of cyanobacterial 3' untranslated DNA sequences to the cryIVB gene did not improve mRNA stability or toxin levels. An analysis of the cryIVB sequence and comparison of codon usage patterns with highly expressed cyanobacterial genes suggest that inefficient translation and intragenic ribosomal binding sites impede protein synthesis and result in rapid turnover of the toxin mRNA.

This report aims to provide a description of the spectrum of radiographic findings in children with AIDS and Pneumocystis carinii pneumonia (PCP). The chest radiographs of all children with perinatally transmitted HIV infection who had PCP were reviewed. Thirty-eight episodes of PCP were noted in 32 children. The age range was 2-17 months. The radiographic findings were characterized as to pattern, severity, presence of pulmonary air cyst, thoracic air leak, thoracic lymphadenopathy, and pleural effusion. The initial distribution of disease was as follows: diffuse (n = 20), patchy (n = 12), focal (n = 4), normal (n = 2). In nearly one-third of children parenchymal abnormalities were mild enough that most normal lung markings were visible. During the course of the illness pneumothorax was noted in eight cases, pulmonary air cyst in five, and pneumomediastinum in one. Pleural effusions were noted in three (5%) cases. Thoracic lymphadenopathy was not observed in any case. The authors concluded that the initial chest radiographic appearance of PCP in children with AIDS is variable. The initial chest radiograph may be normal. The distribution was patchy or focal in nearly one-half of all cases with parenchymal abnormalities. Pulmonary air cysts or thoracic air leaks were noted during the course of the illness in approximately one-third of all cases.

The impact of promoter modification on the expression of the mosquitocidal Bacillus thuringiensis subsp. israelensis cryIVB gene when used to transform the cyanobacterium Synechococcus sp. strain PCC 7942 has been examined. Maximal transcript and protein abundances were achieved by the addition of the lacZ promoter upstream of the cryIVB sequence. Replacement of the endogenous corresponding Bacillus sequences with the Synechococcus petF1 promoter, ribosome binding site, and initiation codon also resulted in increased expression of the cryIVB gene relative to the expression obtained with the Bacillus promoter alone but decreased expression relative to the expression achieved with the tandem array of the Bacillus and lacZ promoters. Synechococcus cells carrying plasmids in which the expression of the cryIVB gene was regulated by either the lacZ or the petF1 promoter were readily consumed by first-instar Culex restuans larvae and proved to be toxic for these organisms.

The authors examined prospectively the prevalence of and relations among patterns of carpal instability in 52 patients with proven rheumatoid arthritis. Posteroanterior, lateral and oblique radiographs of both wrists were obtained. Nineteen patients exhibited one or more patterns of instability. The most common isolated pattern was volar intercalated segmental instability, apparent in six patients. Five patients showed more than one pattern, most commonly a combination of ulnar translocation and volar carpal subluxation. Patients with active erosions or changes in the distal radioulnar joint were more likely to exhibit instability than those without such findings. Carpal instability is a frequent mechanical complication of rheumatoid arthritis. The radiologist should be aware of this possibility, so that a diagnosis can be made promptly and appropriate clinical management begun.

A five year retrospective review of all exposures to a high concentration phenol disinfectant (Creolin Disinfectant 26% phenol) reported to a regional poison center located 96 cases, with 16 cases lost to follow up. There were 60 oral-only exposures, 7 dermal-only exposures and 12 oral/dermal exposure. One patient was an inhalation exposure. Fifty-two cases (65%) were evaluated in a hospital. Eleven patients with oral exposures (14%) experienced rapid CNS depression, but no seizures occurred. Vomiting, coughing, and stridor was noted in 14, 7 and 4 patients respectively. Burns were noted in 17 of 72 (24%) patients with oral exposure and 5 of 19 (26%) with dermal exposure. Seventeen patients underwent endoscopy. Tissue sloughing was noted in one case. All other burns were first degree. No cardiovascular complications occurred. Twenty-eight patients (35%) were followed at home via telephone with one episode of vomiting and one episode of dermal irritation occurring. CNS toxicity from exposure to a high concentration phenol containing cleaning product appears to be rapid in onset. The absence of serious toxicity and major chemical burns in this series does not eliminate concern with the corrosive and systemic risks of phenol poisoning.

The CT scans of 400 consecutive children evaluated with CT following blunt abdominal trauma were evaluated to determine the frequency of periportal low-attenuation zones, assess patterns of associated intraabdominal injury, and examine clinical outcome. Periportal low-attenuation zones were noted in 60 children (15%). The presence of these zones was associated with a significantly higher incidence of intraabdominal injury (60% versus 11%, p = 0.0001). Injuries most frequently associated with zones of periportal low-attenuation included hepatic (n = 23, 38%), and adrenal (n = 14, 23%). Children who had periportal low-attenuation zones tended to be more physiologically unstable as evidenced by a lower Trauma Score (diffuse, 11.9; focal, 13.4) than children without the zones (15.1, p = 0.0001). The presence of these zones was also associated with a significantly higher mortality rate (13% versus 1%, p = 0.0001). Ten children who had periportal low-attenuation zones and no hepatic injury on CT had a normal appearing liver on gross inspection at surgery or autopsy. In conclusion, periportal low-attenuation zones are common in children who have hepatic injury. These zones may be seen in conjunction with non-hepatic visceral injury or in the absence of intraabdominal injury. The presence of zones of periportal low-attenuation is associated with a higher index of physiologic instability, and higher mortality.

The need to attract students to--and keep them in--osteopathic internship and residency programs is great. Recognizing this fact, the osteopathic hospitals, through the American Osteopathic Hospital Association, have placed a renewed focus on liaisons with osteopathic medical education. Voices From the Future represents one such effort. This report reveals how osteopathic medical students, interns, and residents perceive the current state of osteopathic graduate medical education programs as well as the changes that they would like to see incorporated.

Over 90% of the diabetic neurotrophic ulcers treated with the felted foam technique at the Cleveland Foot Clinic have completely healed. The average healing time for plantar ulcers has been approximately 8 weeks. After the ulcerations have healed, molded shoes or orthopedic shoes with Plastazote inserts are prescribed. The felted foam technique is simple to perform in an office setting and can be used by both the novice and the experienced practitioner.

The medical records and CT scans of 34 children with posttraumatic adrenal hemorrhage were reviewed. Adrenal hemorrhage was unilateral in 32 children; most injuries were on the right side. Bilateral hemorrhage was present in two children. The injured gland was oval in 27 cases and triangular in nine. Gland size ranged from 7 to 45 mm long and 4 to 30 mm wide. All adrenal hemorrhages had decreased attenuation relative to liver and spleen on contrast-enhanced CT. Ipsilateral diaphragmatic crural thickening was a frequent (61%) associated finding. Ipsilateral intraabdominal (61%) and intrathoracic (44%) injuries were often present. Clinical signs of adrenocortical insufficiency were not observed in any child. In summary, posttraumatic adrenal hemorrhage is uncommon in children. The hemorrhage is usually unilateral, right sided, and associated with ipsilateral visceral injury.

The purpose of this study is to determine the efficacy of CT in the diagnosis of pancreatic injury after blunt abdominal trauma in children. Pancreatic injury was diagnosed at surgery, at autopsy, or on the basis of the development of clinical pancreatitis or a pseudocyst on follow-up imaging evaluation in 18 of 1045 consecutive children examined with CT after blunt trauma. Types of pancreatic injury included laceration in 11 children, transection in two, contusion in one, and tumor with hemorrhage in one. Three children had clinical pancreatitis without a pancreatic abnormality noted on CT. The pancreatic injury was prospectively identified on CT in 12 children (67%). The presence of fluid in the lesser sac was a useful marker for injury to the pancreas. This was noted in 13 children with pancreatic injury, whereas it was observed in only six (1%) of 1028 children in the absence of pancreatic injury (sensitivity, 72%; specificity, 99%). Fluid in the anterior pararenal space was less helpful in establishing the diagnosis of pancreatic injury (sensitivity, 44%; specificity, 98%). A pancreatic pseudocyst developed in four of the 11 survivors. Our experience shows that direct signs of pancreatic trauma may be difficult to identify on CT. Recognition of the limitations of CT diagnosis of pancreatic injury is important in helping to reduce errors of interpretation.

Twenty-seven of 1,018 children evaluated with contrast material-enhanced computed tomography (CT) after blunt trauma demonstrated a characteristic hypoperfusion complex. This complex was usually seen in young children (median age, 2 years). CT findings in all 27 patients included a dilated, fluid-filled bowel and abnormally intense enhancement of the bowel wall, mesentery, kidneys, aorta, and inferior vena cava. Twenty-four percent of all children with a Trauma Score of 10 or less and 20% with a Glasgow Coma Score of 6 or less had the hypoperfusion complex. All 27 patients had a normal blood pressure immediately before CT, but five (19%) became hypotensive within 10 minutes of intravenous contrast material administration. Twenty-three children (85%) died. Of 16 children who survived 24 hours, four (25%) developed renal insufficiency. The intense multiorgan enhancement pattern seen in the hypoperfusion complex indicates tenuous hemodynamic stability. Recognition that the constellation of CT findings is due to hypovolemic shock and not to injured viscera helps avoid unnecessary laparotomy.

In order to study the ability of freshwater algae and cyanobacteria to form extracellular fibrils, a screening test using ruthenium red (RR) staining was carried out on 28 species. Five of these were examined for growth and production of fibrillar material in culture media of different phosphate (P;) contents. RR-staining and uronic acid determinations at various stages of algal growth were complemented by electron microscopy of the cells and of fibrillar material released into the medium. The lower Pi concentrations enhanced growth of Micrasterias radiata, Eremosphaera sp., and Microcystis aeruginosa, and had little or no effect on growth of a Xanthidium sp. and Scenedesmus quadricauda. Extracellular uronic acid production, which was higher in low Pi medium in M. radiata, M. aeruginosa, and Xanthidium sp., could reach levels of 50 mg/liter or more. Algae with high proportions of RR-positive cells (M. radiata, Eremosphaera sp., Xanthidium sp., and M. aeruginosa) produced high levels of slime-like material and distinct fibrils that were often seen attached to the cell surface and only slowly released into the medium. No such material was found in cultures (or supernatants) of Sc. quadricauda, which also produced relatively low amounts of polyuronic acids. Specific types of filaments, often forming "fascicles" with rectangular arrays of globular particles were observed by negative staining electron microscopy of some algal cultures. RR-positive material was also observed in the cytoplasm and on the cell walls and surfaces of M. radiata and M. aeruginosa.

Primary podiatric care encompasses patient education, disease prevention, diagnosis, treatment, and patient referral. When performed on a regular basis, primary podiatric care can delay or prevent some of the complications associated with the vascularly compromised patient.

The improvement in the anemia in patients with end-stage renal disease (ESRD) on continuous ambulatory peritoneal dialysis (CAPD) suggests that dialyzable substances present in the sera of uremic patients either inhibit erythropoiesis directly or inactivate erythropoietin (EPO). In the present study predialysis sera from patients with ESRD inhibited erythroid colony (CFU-E) (N = 10) formation to a significantly (P less than 0.01) greater degree than granulocyte-macrophage (CFU-GM) (N = 7) colony formation in mouse bone marrow (MBM) cultures. The polyamines spermine (SP) (18 to 560 nm/ml) and spermidine (SD) (4 to 648 nm/ml) exerted a more significant (P less than 0.05) inhibition of CFU-E (N greater than or equal to 5) than that of CFU-GM (N greater than or equal to 5) growth. Concentrations of 0.80, 1.0, and 1.5 nm/ml of putrescine (PU) were 92%, 85%, and 77% of erythroid colony (CFU-E) controls (N = 4) and 104%, 130%, and 127% of CFU-GM controls (N = 4). Putrescine (PU) at 1.5 nm/ml also produced a significant (P less than 0.05) inhibition of CFU-E, whereas CFU-GM were stimulated by PU. These data suggest that predialysis sera from uremic patients, as well as SP, SD, and PU, are selectively more inhibitory to CFU-E than CFU-GM growth. The immunoreactivity of EPO was not significantly changed when it was coincubated with SP, SD and PU and measured by radioimmunoassay. PU was found to inhibit noncompetitively the bioactivity of EPO in a CFU-E assay. These data support the hypothesis that polyamines may be important uremic toxins in the anemia of ESRD.

Adrenal gland size was evaluated in six infants with congenital adrenal hyperplasia. All of the infants had a severe deficiency of the 21-hydroxylase enzyme resulting in the salt-losing form of congenital adrenal hyperplasia. The adrenal measurements were compared with those of 40 consecutive age-matched, asymptomatic infants. Mean adrenal length was 14.4 mm and width was 1.9 mm in asymptomatic infants, whereas in infants with congenital adrenal hyperplasia mean adrenal length was 23.7 mm and width was 5.3 mm. Although infants with congenital adrenal hyperplasia may have normal-sized adrenal glands, mean length measurements of 20 mm or greater and mean width measurements of 4 mm or greater suggest the diagnosis.

In vitro protein synthesis was studied in extracts of the moderate halophile Vibrio costicola by using as mRNAs the endogenous mRNA of V. costicola and the RNA of the R17 bacteriophage of Escherichia coli. Protein synthesis (amino acid incorporation) was dependent on the messenger, ribosomes, soluble cytoplasmic factors, energy source, and tRNA(FMet) (in the R17 RNA system) and was inhibited by certain antibiotics. These properties indicated de novo protein synthesis. In the V. costicola system directed by R17 RNA, a protein of the same electrophoretic mobility as the major coat protein of the R17 phage was synthesized. Antibiotic action and the response to added tRNA(FMet) showed that protein synthesis in the R17 RNA system, but not in the endogenous messenger system, absolutely depended on initiation. Optimal activity of both systems was observed in 250 to 300 mM NH4+ (as glutamate). Higher salt concentrations, especially those with Cl- as anion, were generally inhibitory. The R17 RNA-directed system was more sensitive to Cl- ions than the endogenous system was. Glycine betaine stimulated both systems and partly overcame the toxic effects of Cl- ions. Both systems required Mg2+, but in lower concentrations than the polyuridylic acid-directed system previously studied. Initiation factors were removed from ribosomes by washing with 3.0 to 3.5 M NH4Cl, concentrations about three times as high as that needed to remove initiation factors from E. coli ribosomes. Washing with 4.0 M NH4Cl damaged V. costicola ribosomes, although the initiation factors still functioned. Cl- ions inhibited the attachment of initiation factors to tRNA(FMet) but had little effect on binding of initiation factors to R17 RNA.

From 1981 to 1986, 12 patients with Stage I and II diffuse large cell lymphoma of the mediastinum were treated with 4 or more cycles of multiagent chemotherapy and for nine patients this was followed by mediastinal irradiation. The response to treatment was assessed by three-dimensional volumetric analysis utilizing thoracic CT scans. The initial mean tumor volume of the five patients relapsing was 540 ml in contrast to an initial mean tumor volume of 360 ml for the seven patients remaining in remission. Of the eight patients in whom mediastinal lymphoma volumes could be assessed 1-2 months after chemotherapy prior to mediastinal irradiation, the three patients who have relapsed had volumes of 292, 92, and 50 ml (mean volume 145 ml) in contrast to five patients who have remained in remission with residual volume abnormalities of 4-87 ml (mean volume 32 ml). Four patients in prolonged remission with CT scans taken one year after treatment have been noted to have mediastinal tumor volumes of 0-28 ml with a mean value of 10 ml. This volumetric technique to assess the extent of mediastinal large cell lymphoma from thoracic CT scans appears to be a useful method to quantitate the amount of disease at presentation as well as objectively monitor response to treatment.

Osteochondroma represents the most common benign bone tumor and occurs most frequently in the proximal humerus, tibia, and distal femur. The bones of the foot, by comparison, are less commonly involved. The tumor appears to be a developmental defect of bone preformed in cartilage rather than a true neoplasm. However, on rare occasions it may undergo chondrosarcomatous degeneration, thus demonstrating neoplastic behavior. A review of the literature, including clinical features of osteochondroma, radiologic and histologic characteristics, and theories on pathogenesis, is presented. Information concerning principles of surgical treatment, techniques of diagnosis, and facts to aid in the differential diagnosis of osteochondroma is presented also. Finally, a series of case reports is presented to demonstrate the surgical treatment of osteochondroma of the foot. Included are three cases of phalangeal osteochondroma, one of metatarsal osteochondroma, and an unusual report of osteochondroma of the talus. A case report and discussion of a patient with juxtacortical circumscripta myositis ossificans of the foot is also presented to demonstrate how information on lesions included in the differential of osteochondroma can be utilized clinically to make the diagnosis.

Intact cells of Vibrio costicola hydrolyzed ATP, ADP, and AMP. The membrane-bound 5'-nucleotidase (C. Bengis-Garber and D. J. Kushner, J. Bacteriol. 146:24-32, 1981) was solely responsible for these activities, as shown by experiments with anti-5'-nucleotidase serum and with the ATP analog, adenosine 5'-(beta gamma-imido)-diphosphate. Fresh cell suspensions rapidly accumulated 8-14C-labeled adenine 5'-nucleotides and adenosine. The uptake of ATP, ADP, and AMP (but not the adenosine uptake) was inhibited by adenosine 5'-(beta gamma-imido)-diphosphate similarly to the inhibition of the 5'-nucleotidase. Furthermore, the uptake of nucleotides had Mg2+ requirements similar to those of the 5'-nucleotidase. The uptake of ATP was competitively inhibited by unlabeled adenosine and vice versa; inhibition of the adenosine uptake by ATP occurred only in the presence of Mg2+. These experiments indicated that nucleotides were dephosphorylated to adenosine before uptake. The hydrolysis of [alpha-32P]ATP as well as the uptake of free adenosine followed Michaelis-Menten kinetics. The kinetics of uptake of ATP, ADP, and AMP also each appeared to be a saturable carrier-mediated transport. The kinetic properties of the uptake of ATP were compared with those of the ATP hydrolysis and the uptake of adenosine. It was concluded that the adenosine moiety of ATP was taken up via a specific adenosine transport system after dephosphorylation by the 5'-nucleotidase.