HMO behavior and stock market valuation: what does Wall Street reward and punish?

This article analyzes the variation in returns to owning stock in investor-owned health maintenance organizations (IOHMOs) for the period 1994-1997. The average return (measured by the change in the market value of the stock plus dividends) was close to zero, but returns were positive and high for firms operating in local markets that were and remained less competitive, with large nationwide scope, and with less rapidly growing panels of contracted physicians. Indicators of a firm's strategic direction were abstracted from their annual reports; firms pursuing a merger or acquisition strategy, and those emphasizing a utilization review strategy, showed lower returns than those that did not. Other strategy and market variables were not related to stock market returns over this period, and were also generally not related to price-earnings ratios. This analysis supports the view that competitive HMO markets best constrain profits to investor-owned firms.

Variations in cell and structure populations along the length of murine small intestine.

Previous workers have reported a range of structural variations occurring along the length of small intestine. These studies have concentrated on the major intestinal components with little information available on the intersite variation of other members of a highly heterogeneous population. Using resin histology, the current study has collected data per circumference for all definable structural features within the murine intestinal wall, along with measurements for epithelial, muscle, nerve and connective tissue areas, and villous height and cryptal depth. Seven different sites along the length of the small intestine were examined. Following statistical comparisons a number of features exhibited no intersite variation; these were numbers of villi, submucosal vessels, myenteric nerve plexus profiles, inner muscle nuclei and apoptotic bodies as well as measurements for tissue areas and cryptal depth. Variations were seen between sites for crypts, enterocytes, villous and cryptal stromal cells, cryptal goblet cells, cryptal non-secretory epithelial cells, Paneth cells, endocrine cells, intra-epithelial lymphocytes, submucosal nerve plexus profiles, outer muscle nuclei and mitotic figures. A reduced villous height was observed caudally. Certain correlations between villous height/crypt number and constituent parameters have been noted. The results provide a complete description of how each definable structural feature within the gut wall varies at regular intervals along the length of the small intestine in C57 BL mice. A number of previously unreported variations have been described. The work provides a comprehensive data bank for future intestinal investigations.

Acute and protracted radiation effects on small intestinal morphological parameters.

PURPOSE: To compare the responses of small intestinal morphological parameters after acute and protracted doses of radiation. MATERIALS AND METHODS: Male C57BL6 mice were examined 6, 24 and 72 h after whole body gamma-irradiation, given either as an acute 5 Gy dose, or as a protracted (continuous) dose of 20 cGy per day for 25 days to a total dose of 5 Gy. Many different structural parameters at both the light microscopical and ultrastructural levels were assessed quantitatively. RESULTS: At different time points following both schedules there were changes in the number of villous enterocytes, goblet cells, lamina propria cells and mitotic figures. Ultrastructural changes occurred in the epithelium. Many of the parameters that showed changes following the protracted schedule appeared to be returning to normal within 3 days of the cessation of radiation, a finding which was in contrast with the acute dose. The protracted schedule produced increases in the number of Paneth cells and in the length of enterocyte microvilli. CONCLUSIONS: Many of the responses that occurred after the protracted schedule suggest that adaptive mechanisms may be being triggered following persistent exposure to radiation.

Imbrication versus excision for fascial healing.

BACKGROUND: The purpose of this study was to determine whether imbrication of native fascia versus excision and closure of new raw fascia forms a stronger union. METHODS: We utilized the anterior rectus sheath fascia of Sprague-Dawley rats as the model. Sixty rats underwent fascial tightening procedures. Each rat had the anterior rectus sheath shortened by 1 cm, 30 by imbrication and 30 by excision and closure. Ten of each group were harvested at 7 days' healing, 10 at 14 days, and 10 of each group at 28 days' healing. The anterior rectus sheath was removed, a "dumbbell" shape constructed, and the cross sectional area at the point of interest determined. The fascia was placed on an Instron tensiometer to determine the breaking strength. Tensile strength was calculated and the data analyzed by ANOVA and the Kruskall-Wallis test. Tissue samples of the closures were histologically analyzed for fibroblast counts, degree of inflammation, and presence of dense fibrous connective tissue. Tissue samples were also analyzed for enzymatic collagen crosslinking. RESULTS: There was a statistically significant difference in tensile strength between the two groups at 7, 14, and 28 days. Results show that at 7 days the mean tensile strength of excision was 0.133 kg/mm2 +/- 0.056 and the mean tensile strength of imbrication was 0.083 kg/mm2 +/- .048 (P < 0.05); at 14 days the mean tensile strength of excision was 0.105 kg/mm2 +/- 0.033 and the mean tensile strength of imbrication was 0.057 kg/mm2 +/- 0.014 (P < 0.002), and at 28 days the mean tensile strength of excision was 0.279 kg/mm2 +/- 0.143 and the mean tensile strength of imbrication was 0.145 kg/mm2 +/- 0.061 (P < 0.03). Histologic findings showed no statistical significance between the two closure methods when comparing degree of inflammation or the number of fibroblasts present. However, at 7 and 14 days there is a significantly greater presence of dense fibrous connective tissue in the excision group (P < 0.03 at 7 days and P < 0.044 at 14 days by ANOVA). Collagen crosslink analysis showed that by day 28 there is a significantly greater amount (P < 0.05 by ANOVA) of the difunctional crosslink dihydroxylysinonorleucine (DHLNL) and a greater ratio between DHLNL and the difunctional crosslink hydroxylysinonorleucine (HLNL) in the excision and closure group. CONCLUSION: We conclude that at 7, 14, and 28 days healing, excision provides a significantly stronger closure than imbrication. According to the crosslinking analysis, it is likely that this strength advantage may continue to increase over time. These findings suggest that excision and closure may be the preferred method for fascial tightening procedures.

Morphological profiles of neutron and X-irradiated small intestine.

This paper describes the response of mouse small intestine, at several time points after treatment with neutron or X-irradiation, using doses expected to give similar effects in terms of crypt/microcolony survival. Using resin histology, the effects of radiation on the numbers of duodenal cell types and measurements of tissue areas were assessed. The results for individual parameters and for an estimate of overall damage are given in a data display, which summarises the morphological profile of the organ after both types of radiation. Damage and recovery were seen for many of the parameters studied but there was no standard response pattern applicable for all parameters. In particular, the response of individual crypt cell types could not be predicted from knowledge of the change in crypt numbers. With regard to the holistic response of the gut, neutron irradiation appeared to have caused more damage and produced more early effects than the X-irradiation. More specifically, neutron treatment led to more damage to the neuromuscular components of the wall, while X-irradiation produced early vascular changes.

A morphological and microanalytical investigation into the uptake of particulate iron across the gastrointestinal tract of rats.

The uptake and translocation of particulate iron across the gastrointestinal (GI) mucosa of young adult rats has been investigated using a range of morphological techniques and X-ray microanalysis (XRMA). In animals fed a suspension of iron powder constituted of metallic iron particles ranging in size from 6-9 microns down to 5-30 nm, light microscopic histochemistry has clearly revealed iron deposits within the tissues of the duodenum. Scanning electron microscopy of the duodenal tissue by back-scattered electron imaging has complemented the light microscopic observations and revealed a selective localization of iron in the villi with variation in levels of iron uptake by the mucosal cells. Ultrastructural and XRMA analysis of duodenum has established the presence of metallic iron nanoparticles within the brush border, lateral intercellular spaces of the mucosal cells, mitochondrial cristae and cytoplasm of both mucosal and stromal cells. The observations indicate that metallic iron particles, in the nano-size range, may be taken up by the GI mucosa and that the passage of such particles across the epithelial barrier may take place through both a paracellular as well as a transcytotic process.

Heavy ion induced changes in small intestinal parameters.

The effects on 17 different structural parameters of mouse small intestine three days after treatment with three types of heavy ion (neon, iron and niobium) are compared, the first two being of particular relevance to space flight. The data for niobium are given in full, showing that changes after niobium ion treatment are not standard and are concentrated in the epithelial compartment, with few of the parameters having a response which is dose dependent. When comparisons are made for the three types of heavy ion, the damage is greatest after neon ion irradiation, implying that the additional non-epithelial damage produced as LET rises from X rays through neutrons to neon ions is not necessarily maintained as LET continues to rise. Further understanding is therefore needed of the balance between changes affecting the vascular and absorptive components of the organ. Variation from group to group is also important, as is variation of strain or gastrointestinal status. All such factors are important in the understanding of changes in multicellular organs after exposure to heavy ion radiation.

Microwave elution of red cell antibodies.

Using a commercial microwave oven (750 W, 2,450 MHz), we compared the use of microwave energy to the commonly used method of acid-glycine elution (Elu-Kit II, Gamma Biologicals, Houston, Tex., USA) to elute antibodies from direct antiglobulin test positive red blood cells (RBC). Using a 33% suspension of RBCs in cold saline (1-6 degrees C) in a polypropylene test tube, the microwave technique was comparable for eluting Rh (except anti-c and anti-e) and Kell and superior for eluting Duffy, Kidd antibodies while acid-glycine was superior in eluting S and s antibodies. Consistent results were obtained using the microwave technique when the RBC suspension reached temperature of 57-64 degrees C. Heat or the rate of temperature rise appears to play an important role in the microwave elution process although other not yet identified microwave properties may also be a factor. Microwaves are a quick (8 s) alternative to well-established methods of elution and have shown to give consistent results in our study. Commercially available microwave ovens vary substantially in power, making it necessary to perform an initial calibration of the microwave in order to determine a location within the microwave cavity where exposure to microwaves will consistently achieve temperatures of 57-64 degrees C in all cell suspensions.

Microwave dissociation of antigen-antibody complexes: a new elution technique to permit phenotyping of antibody-coated red cells.

To evaluate the effectiveness of microwave irradiation in dissociating IgG from red cells (RBCs), the use of chloroquine diphosphate (CDP) was compared to that of microwaves. Fifteen paired samples of RBCs from 15 patients with positive direct antiglobulin tests (DATs) were treated with both CDP and microwave radiation. Total microwave exposure times ranged from 20 to 100 seconds. Posttreatment DATs were performed, and the reaction grades of the posttreatment DATs were compared. RBC phenotyping was also performed on repeatedly microwaved RBCs to demonstrate possible effects on RBC antigen expression. Microwaves successfully reduced the reaction grade of the DAT in 14 of 15 samples; CDP reduced the reaction grade in 12 of 15 samples. In samples with a DAT of 2+ or greater (n = 13), the microwave method yielded a greater reduction in DAT strength in six cases (results in the other 7 cases were identical with both methods) (p = 0.01). Five of eight cases with a DAT of 3+ showed a greater reduction in the DAT with microwave treatment than with CDP treatment; results in the remaining three cases were identical (p = 0.03). RBC antigenicity remained unchanged after exposure to microwave radiation (A, B, C, c, D, E, e, Fya, Fyb, Jka, Jkb, K, k, S, and s). Microwave treatment required less than 10 minutes per sample, while CDP treatment required 30 to 120 minutes per sample (mean, 88 min). The microwave technique of antigen-antibody dissociation from RBCs provides a rapid and accurate method of facilitating the phenotyping of RBCs coated with warm autoantibodies and is superior to other methods, which destroy RBC antigens.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between villous shape and mural structure in neutron irradiated small intestine.

Previous work on irradiation of mouse small intestine has assessed the changes produced by counting crypts/microcolonies, scoring villous shape or examining morphological changes in specific parts of the wall. This paper used scanning and transmission electron microscopy to study the effects of whole body irradiation with 5 Gy neutrons on the surface and internal features of the intestinal wall of CFLP mice, 1 day, 3 days and 7 days after treatment. Empirical scores from the ultrastructural findings were inserted into a Morphological Index display calculated from analytical data based on cell counts and area measurements obtained from resin histology sections. The final data display showed that the neutron irradiation produced marked structural changes in different cells and tissues by 1 day. These changes were maximal at 3 days with substantial improvement by 7 days. When this data display was compared with scores taken from scanning electron microscopy of the mucosal surface, the change in villous shape from erect fingerlike projections to lower profiles less suited to absorption was seen to correlate more with changes in the smooth muscle than with the epithelial cryptal compartment.

Characterization through a data display of the different cellular responses in X-irradiated small intestine.

Previous work on small intestinal radiation injury has reported changes in epithelial and non-epithelial tissues, but with few quantitative comparisons of different responses by individual cell types. The approach used here quantifies the responses of mouse duodenum to X-irradiation with 6 Gy, 10 Gy and 20 Gy, sampled three days after treatment, and 10 Gy sampled 6 hours, 1 day and 3 days after treatment. Tissue area measurements and counts per circumference for 13 different structural elements are subjected to statistical tests. New data reported here for X-irradiation include the fact that cryptal cells do not respond uniformly, indicating that the crypt/microcolony cannot always be used as a standard unit in assessing radiation injury. Non-epithelial structures, such as submucosal arterioles, are also affected. The data display also includes control-referenced ratios, from which are calculated Tissue Indices and a final Morphological Index, which estimates total structural damage. The Indices are useful in drawing attention to unexpected changes in extent or range of data sets. In addition, the Epithelial Index appears to be a sensitive indicator of radiation damage, even at low doses and early time points. The data display includes a graph of the total Indices and summary tables of data, and encourages close study of the constituent data points.

Neutron and X-ray effects on small intestine summarized by using a mathematical model or paradigm.

The responses of intestinal tissues to ionizing radiation can be described by comparing irradiated cell populations qualitatively or quantitatively with corresponding controls. This paper describes quantitative data obtained from resin-embedded sections of neutron-irradiated mouse small intestine at different times after treatment. Information is collected by counting cells or structures present per complete circumference. The data are assessed by using standard statistical tests, which show that early mitotic arrest precedes changes in goblet, absorptive, endocrine and stromal cells and a decrease in crypt numbers. The data can also produce ratios of irradiated: control figures for cells or structural elements. These ratios, along with tissue area measurements, can be used to summarize the structural damage as a composite graph and table, including a total figure, known as the Morphological Index. This is used to quantify the temporal response of the wall as a whole and to compare the effects of different qualities of radiation, here X-ray and cyclotron-produced neutron radiations. It is possible that such analysis can be used predictively along with other reference data to identify the treatment, dose and time required to produce observed tissue damage.

Ultrastructure of the excretory system of Trilocularia acanthiaevulgaris (Cestoda, Tetraphyllidea).

The fine structure of the excretory system in the juvenile (plerocercoid-like) form of Trilocularia acanthiaevulgaris is described. The flame cell bears a bunch of 50-70 cilia, which are anchored in the cytoplasm by means of basal bodies possessing striated rootlets. All the cilia in the "flame" are aligned in the same direction. The flame and duct cells are connected by interdigitating ribs of cytoplasm separated by a fibrous sheet. Both internal and external leptotriches are also present. The lumen of the excretory ducts is intracellular in origin. The apical surface of the cytoplasm lining the duct is convoluted and its surface area is further amplified by means of microvilli. The fine structure of the excretory system in this primitive tapeworm is compared with that described for other parasitic and free-living flatworms.

Early morphological changes in blood capillaries of mouse duodenal villi induced by X-irradiation.

The mouse has been used extensively as a model for radiobiological studies. In particular, the cellular compartments of the intestinal villi have been examined, in an effort to gain an understanding of the gastrointestinal disturbances which follow radiotherapy of the abdomen. The response of the blood vessels has been, however, largely neglected. This paper examines the early response of the duodenal capillaries to an X-ray dose of 10 Gy using conventional light and transmission electron microscopy. The villous capillaries were examined at 6 h, 1 day and 3 days after treatment. The results showed that the capillaries responded to X-irradiation within 6 h. exhibiting marked vasodilation similar to that observed in acute inflammation. Significantly there was no ultrastructural evidence of endothelial cell disruption or loss of junctional attachment between the cells, but the characteristic fenestrae of these vessels were less apparent than in the controls. One day after treatment the capillaries had become constricted, with many vessels totally non-patent. The cytoplasm and nuclei of the endothelial cells showed changes consistent with vascular damage, such as nuclear shape alterations and luminal cytoplasmic projections. Three days after treatment there was variation in the capillary patency, as some vessels showed signs of incipient necrosis whilst others were relatively normal in appearance. The results suggest that the early vascular response typically involves a phase of vasodilation followed by constriction within the first 24 h after treatment, a finding consistent with the radiation response of skin capillaries in what has been described as 'transient erythema'. The ultrastructural changes associated with the phasic changes in patency did not suggest large scale endothelial death, but rather alteration of the functional capacity of the vessels which may in turn affect the other cell populations in the villi.

An ontogenetic study of the cholinergic and serotoninergic nervous systems in Trilocularia acanthiaevulgaris (Cestoda, Tetraphyllidea).

The localisation and distribution of the cholinergic and serotoninergic components of the nervous system in the plerocercoid, adult and free proglottis stages of the tetraphyllidean tapeworm Trilocularia acanthiavulgaris were determined by enzyme histochemical and immunocytochemical techniques. The central nerve ring (CNR) in the scolex contains two lateral ganglia and gives rise to five pairs of longitudinal nerve cords (LNC's; three lateral, two median). The nerve cords run posteriorly throughout the bodies of the plerocercoid and adult worms and the free proglottis. Nerves from the CNR and accessory lateral LNC's pass to the bothridia, where they give rise to extensive nerve plexuses. As the individual proglottides develop along the strobila, a small nerve ring forms at the anterior end of each proglottis; within the nerve ring, distinct bilateral ganglia develop prior to the release of the proglottis. All ten LNC's are present in the free proglottis. The genital atrium and cirrus sac are innervated by cholinergic and serotoninergic elements. The cholinergic nervous system predominates in the CNS within the scolex, whereas there is a larger population of 5-HT-immunoreactive nerve cells associated with the LNC's and segmental ganglia along the strobila and within the free proglottis.

The structure, composition, formation and possible functions of calcareous corpuscles in Trilocularia acanthiaevulgaris Olsson 1867 (Cestoda, Tetraphyllidea).

Mature calcareous corpuscles in the juvenile (stomach) worms of Trilocularia acanthiaevulgaris comprise a number of concentric lamellae interspersed with areas of flocculent material. Each lamella is composed of a pair of membranous rings to which amorphous, non-crystalline material is attached. The process of corpuscle formation is intracellular, beginning with the autophagic break-down of the cytoplasm to produce a central vacuole within a parenchymal cell. The vacuole enlarges until only a thin layer of cytoplasm remains at the periphery and the nucleus is displaced to one end of the cell. Paired, concentrically arranged membranes are laid down beneath the peripheral cytoplasmic layer and eventually occlude the central vacuole. X-ray analysis of the corpuscles indicates the presence of calcium, phosphorus, sulphur, zinc and molybdenum, with the major peaks representing calcium, phosphorus and sulphur. Calcium appears to be bound to the lamellae rather than associated with the material between lamellae. The possible functions of the corpuscles are discussed in relation to the biology of T. acanthiaevulgaris and its developmental sequence in the dogfish gut.

The seasonal occurrence of Trilocularia acanthiaevulgaris (Cestoda: Tetraphyllidea) from spiny dogfish in the Irish Sea.

Trilocularia acanthiaevulgaris occurs in the stomach and spiral valve of the spiny dogfish. Statistical analyses show that the stomach and spiral valve worms of male fish and the stomach worms of female fish exhibit seasonal trends in prevalence and mean worm burden, with peaks occurring in May, June and July of each year. Spiral valve worms of female fish do not show this trend. Calculation of the product-moment correlation coefficient shows that the peak in the number of stomach worms occurs approximately 1 month before that of spiral valve worms in male fish. Strobilization of the adult spiral valve worms and development of the resulting free proglottides is also seasonal, and takes place in June/July in both sexes. Seasonal trends in prevalence, mean worm burden and maturation of T. acanthiaevulgaris may be related to water temperature, and the cyclical changes in levels of reproductive hormones and thyroid activity associated with migration and mating of spiny dogfish. It is suggested that the availability of infected intermediate hosts and diet of the dogfish may also be important in explaining the seasonality of infection.