Use of a Clostridium perfringens vector to express high levels of SIV p27 protein for the development of an oral SIV vaccine

Clostridium perfringens is a normal bacterial flora of the small and large intestines of humans and other animals. The current study investigates the potential use of a noncytotoxic C. perfringens as an oral vaccine vehicle for expression and intestinal delivery of a large amount of SIV antigens. Here we report the construction of a recombinant C. perfringens vaccine vector expressing high levels of SIV p27 during sporulation. Following oral administration of this recombinant C. perfringens vaccine vector to mice, large amounts of intact p27 protein were detected in the terminal ileum where the majority of Peyer's Patches (PPs) are located. Furthermore, dendritic cells (DCs) beneath the mucosal surface in the PPs were able to capture SIV p27 antigen, when PPs were exposed to C. perfringens expressing SIV p27 antigen. In addition, uptake of C. perfringens was able to induce maturation of mouse DCs. These results support the potential use of C. perfringens as an oral SIV/HIV vaccine vector.     

Pressure-flow relations in coronary circulation

The blood vessels that run on the surface of the heart and through its muscle are compliant tubes that can be affected by the pressures external to them in at least two ways. If the pressure outside these vessels is higher than the pressure at their downstream ends, the vessels may collapse and become Starling resistors or vascular waterfalls. If this happens, the flow through these vessels depends on their resistance and the pressure drop from their inflow to the pressure around them and is independent of the actual downstream pressure. In the first part of this review, the physics of collapsible tubes is described, and the possible occurrences of vascular waterfalls in the body is evaluated. There is good evidence that waterfall behavior is seen in collateral coronary arteries and in extramural coronary veins, but the evidence that intramural coronary vessels act like vascular waterfalls is inconclusive. There is no doubt that in systole there are high tissue pressures around the intramyocardial vessels, particularly in the subendocardial muscle of the left ventricle. The exact nature and values of the forces that act at the surface of the small intramural vessels, however, are still not known. We are not certain whether radial (compressive) or circumferential and longitudinal (tensile) stresses are the major causes of vascular compression; the role of collagen struts in modifying the reaction of vessel walls to external pressures is unknown but possibly important; direct examination of small subepicardial vessels has failed to show vascular collapse. One of the arguments in favor of intramyocardial vascular waterfalls has been that during a long diastole the flow in the left coronary artery decreases and reaches zero when coronary arterial pressure is still high: it can be as much as 50 mmHg in the autoregulating left coronary arterial bed and approximately 15-20 mmHg even when the vessels have been maximally dilated. These high zero flow pressures, especially during maximal vasodilatation, have been regarded as indicating a high back pressure to flow that is due to waterfall behavior of vessels that are exposed to tissue pressures.(ABSTRACT TRUNCATED AT 400 WORDS)     

Accumulation and effects of lead and cadmium on wood ducks near a mining and smelting complex in Idaho

A study of wood ducks (Aix sponsa) was conducted along the Coeur d'Alene River system in northern Idaho in 1986 and 1987. Most of this area has been subjected to severe contamination from lead and other metals from mining and smelting since the 1880s. In 1986, a preliminary study of wood duck nesting was conducted in the contaminated area; incubating hens captured in nest boxes were bled and weighed. Blood samples were used to determine lead and cadmium concentrations and physiological characteristics. In 1987, an intensive study of wood ducks involved trapping and monitoring nest boxes in the contaminated area. Blood and tissue samples were also taken from wood ducks from a reference area without known contamination from metals. Lead levels in blood and tissues of most wood ducks from the contaminated area frequently exceeded those considered hazardous to birds; maximum levels (wet weight) of lead were 8 g g^–1 in blood and 14 g g^–1 in liver. Changes in physiological characteristics constituted the only evidence of potentially adverse effects from lead. In the contaminated area, nesting success (55% unadjusted, 35% Mayfield estimate) was less than in other areas where predation was low and nest boxes were used; but lead concentrations and physiological characteristics of blood were similar in successful and unsuccessful hens.Values of ALAD, hemoglobin, and body mass were negatively correlated with blood concentrations of lead, whereas protoporphyrin was positively correlated with lead levels in the blood. Some of the protoporphyrin values (1,091 g dl^–1 in a male and 756 g dl^–1 in a female) equalled those associated with lead toxicosis in experimental birds. ALAD activity was low in most birds from the contaminated area; values of 0 were obtained from 11 birds. Lead levels in blood, ALAD, protoporphyrin, and hemoglobin were significantly different between birds from the contaminated and reference areas. Concentrations of lead in ingesta of wood ducks ranged from 0.9 to 610 g g^–1 in the contaminated area and 0.2 to 0.6 g g^–1 in the reference area. Levels of cadmium in kidneys of wood ducks ranged from 1g g^–1 to 20 g g^–1 in the contaminated area and from only to 0.1 g g^–1 to 1 g g^–1 in the reference area. Cadmium concentrations were less than known effect levels.     

Redo hepatic resection for metastatic colorectal carcinoma

Redo hepatic resection for recurrent colorectal metastasis was performed in eight patients. There was no operative mortality; major morbidity occurred in 25% and minor morbidity in 13% of patients. Four patients are alive and disease-free at 9, 23, 39, and 49 months, respectively, after their repeat hepatic resection. Four patients have died of recurrent disease, with a median time to recurrence of 6 months and median survival of 15 months. Patterns of failure include hepatic failure alone in two patients and pulmonary and hepatic failure in two. Repeat liver resection can be performed safely and may be beneficial in some patients with recurrent metastases confined to the liver after previous hepatic metastasectomy.

---

Resumen El tratamiento quirúrgico de las metástasis hepáticas recurrentes luego de una resección inicial no ha sido considerado como opción terapeútica. Sin embargo, varios informes recientes han documentado el hecho de que la resección repetida es técnicamente factible y que puede resultar en prolongados intervalos libres de enfermedad en 38% a 50% de los pacientes. Con anterioridad al présente reporte, solo 62 pacientes sometidos a resección hepática repetida por cancer colorrectal metastásico han sido descritos en la literatura. Se requieren estudios adicionales, y nuestro grupo présenta su experiencia para complementar esta base de datos.Se describe la resección redo-hepática por metástasis colorrectales recurrentes en ocho pacientes. No hubo mortalidad operatoria, se registró morbilidad mayor en 25% y menor en 13%. Cuatro pacientes se encuentran vivos y libres de enfermedad a los 9, 23, 39 y 49 meses después de la nueva resección hepática. Cuatro pacientes han muerto por enfermedad récurrente con un tiempo medio de recurrencia de 6 meses, y un tiempo medio de sobrevida de 15 meses. Los lugares de falla incluyen sólo dos en el hígado y dos en el pulmón. La resección repetida del hígado puede ser realizada con seguridad y puede ser beneficiosa en algunos pacientes con metástasis récurrentes confinadas al hígado después de una metastasectomía previa.

---

Résumé La résection itérative de métastases hépatiques d'un cancer colorectal a été pratiquée chez 8 patients. Il n'y a eu aucune mortalité opératoire. La morbidité majeure a été de 25% (2 patients), alors qu'elle a été mineure chez un patient (13%). Quatre patients sont en vie et apparement sans maladie à 9, 23, 39, et 49 mois après leur deuxième résection. Quatre patients sont morts de récidive avec une médiane d'intervalle libre avant la récidive de 6 mois, et une survie médiane de 15 mois. La récidive a été dans deux cas au niveau du foie seul et dans deux autres cas, simultanément au niveau du poumon et du foie. La résection itérative de métastases hépatiques est faisable avec sûreté et peut apporter un plus chez certains patients déjà opérés de leur métastase.

     

Dietary intake of Americans reporting adherence to a low cholesterol diet (NHANES II).

We studied the dietary intake of persons age 18 and over participating in the 1976-80 National Health and Nutrition Examination Survey (NHANES II). We compared the diets of those on a "low cholesterol" diet (dieters, n = 296) with the diets of individuals not following a special diet (non-dieters, n = 10,052). Dietary intakes were assessed by 24-hour recall and food frequency reports and were adjusted for differences in age, sex, race, education, smoking, and socioeconomic status by multivariate statistical techniques. Dieters consumed 16 percent (99% confidence interval(-) -24, -9 fewer calories than non-dieters, and had decreased intake of saturated fat by 25 percent (-34, -15) and cholesterol by 21 percent (-32, -10). However, their intake of vitamin A, thiamine, riboflavin, niacin, calcium, and iron were not significantly different from non-dieters and their ascorbic acid intake was 18 percent (1, 36) higher. The nutrient density (nutrient/1000 kcal) among dieters was increased over non-dieters by 35 percent (-3, 72) for vitamin A, 35 percent (1, 70) for thiamine, 30 percent (-4, 65) for riboflavin, 27 percent (9, 44) for niacin, 60 percent (40, 80) for vitamin C, 14 percent for calcium (-5, 32), and 15 percent for iron (6,25). Compared with non-dieters, dieters consumed 27 percent (9, 45) more poultry and 39 percent (12, 66) more fish, but consumed 30 percent (-44, -16) less eggs and 15 percent (-24, -6) less meat.     

Use of psychoactive substances in three medical specialties: anaesthesia,medicine and surgery

In order to determine the prevalence of psychoactive substance use in three specialty groupings, 1,624 questionnaires were sent to physicians in medicine, surgery and anaesthesia; all had trained at the same academic institution. A response rate of 57.8% was achieved. Comparison of prevalence of impairment rates showed no differences between Surgery (14.4%), Medicine (19.9%) and Anaesthesia (16.8%). Substance abuse was clearly associated with a family history of abuse; 32.1% of the abusers had a family history of such abuse compared with 11.7% of the non-abusers. Increased stress at various career stages did not appear to increase substance abuse; problem areas during medical life times were similar for each specialty. Substances most frequently used were marijuana (54.7%), amphetamines (32.9%); and benzodiazepines (25.1%). Seventy-three used psychoactive drugs which were non-prescribed. Drug counselling programmes were judged inadequate by most. Use of alcohol and drugs by faculty members was reported by a number of respondents.     

Pharmacodynamics of Phenobarbital Anesthesia and Pentylenetetrazol-Induced Maximal Seizures in a Rat Model of Neoplastic Spinal Cord Compression

The purpose of this investigation was to determine whether paraplegia induced by neoplastic cord compression affects the pharmacodynamics of phenobarbital general anesthesia or of pentylenetet-razol (PTZ)-induced convulsions. Paraplegic rats harboring a thora-columbar epidural tumor, or an identical hindlimb tumor mass, received an i.v. infusion of phenobarbital until the onset of anesthesia. At that point, the phenobarbital concentrations in the CSF and serum were measured. Similarly, PTZ was infused until the onset of maximal seizures. It was found that changes related to systemic tumor growth and newly developed paraplegia due to neoplastic spinal cord compression did not attenuate the pharmacodynamics of phenobarbital. However, sustained paraplegia of 4 days duration reduced CNS sensitivity to the hypnotic action of the barbiturate as evidenced by the higher cerebrospinal fluid phenobarbital concentration required to induce anesthesia (170 ± 31 vs 125 ± 20 mg/L; P < 0.05). On the other hand, sustained paraplegia did not affect brain threshold concentration for PTZ-induced seizures.     

Model study detecting breast cancer cells in peripheral blood mononuclear cells at frequencies as low as 10(-7).

A flow cytometric assay was developed to detect rare cancer cells in blood and bone marrow. Multiple markers; each identified by a separate color of immunofluorescence (yellow and two shades of red), are used to reliably identify the cancer cells. Blood or bone marrow cells, which are not of interest but interfere in detecting the cancer cells, are identified by a panel of immunofluorescence markers, each of which has the same color (green). Thus, the rare cancer cells of interest are yellow and two different shades of red but not green. The requirement that the rare cancer cell be simultaneously positive for three separate colors (the specific markers) and negative for a fourth color (the exclusion color) allowed detection of as few as one cancer cell in 10(7) nucleated blood cells (a frequency of 10(-7). To test this rare-event assay prior to clinical studies, a model study was performed in which the clinical sample was simulated by mixing small numbers of cells from the breast carcinoma line BT-20 with peripheral blood mononuclear cells. We detected statistically significant numbers of BT-20 cells at mixing frequencies of 10(-5), 10(-6), and 10(-7). In control samples, no target events (BT-20) were observed when more than 10(8) cells were analyzed. For additional confirmation that the BT-20 cells in the model study were correctly identified and counted, the BT-20 cells (and only BT-20 cells) were covalently stained with a fifth fluorescence dye, 7-amino-4-chloromethylcoumarin (CMAC). CMAC fluorescence data were not used in the assay for detecting BT-20 cells. Only after the analysis using data from the specific and exclusion colors had been completed were the events identified as BT-20 cells checked for CMAC fluorescence. The putative BT-20 events were always found to be positive for CMAC fluorescence, which further increases confidence in the assay. Manual data analysis and an automated computer program were compared. Results were comparable with the manual and automated methods, but the automated "genetic algorithm" always found more BT-20 events. Cell sorting of BT-20 cells from samples that contained BT-20 at frequencies of 10(-5), 10(-6), and 10(-7) provided further evidence that these rare cells could be reliably detected. The good performance of the assay with the model system will encourage further studies on clinical samples.