Acute CO2 tolerance in fishes is associated with air breathing but not the Root effect, red cell ßNHE, or habitat.

High CO2 (hypercapnia) can impose significant physiological challenges associated with acid-base regulation in fishes, impairing whole animal performance and survival. Unlike other environmental conditions such as temperature and O2, the acute CO2 tolerance thresholds of fishes are not understood. While some fish species are highly tolerant, the extent of acute CO2 tolerance and the associated physiological and ecological traits remain largely unknown. To investigate this, we used a recently developed ramping assay, termed the Carbon Dioxide maximum (CDmax), that increases CO2 exposure until loss of equilibrium (LOE) is observed. We investigated if there was a relationship between CO2 tolerance and the Root effect, ß-adrenergic sodium proton exchanger (ßNHE), air-breathing, and fish habitat in 17 species. We hypothesized that CO2 tolerance would be higher in fishes that lack both a Root effect and ßNHE, breathe air, and reside in tropical habitats. Our results showed that CDmax ranged from 2.7 to 26.7 kPa, while LOE was never reached in four species at the maximum PCO2 we could measure (26.7 kPa); CO2 tolerance was only associated with air-breathing, but not the presence of a Root effect or a red blood cell (RBC) ßNHE, or fish habitat. This study demonstrates that the diverse group of fishes investigated here are incredibly tolerant of CO2 and that although this tolerance is associated with air-breathing, further investigations are required to understand the basis for CO2 tolerance.

Phenotypic shift of small intestinal intra-epithelial type 1 innate lymphoid cells in celiac disease is associated with enhanced cytotoxic potential.

The small intestinal (SI) epithelium harbors a heterogeneous population of lymphocytes that mediate mucosal damage and repair in celiac disease (CD). The composition and roles of human proximal SI intra-epithelial innate lymphoid cells (ILCs), and their alterations in CD, are not well understood. We report that duodenal intra-epithelial ILCs predominantly consist of natural killer (NK)p44+ CD127- cytotoxic ILC1s and NKp44- CD127+ helper ILC1s, while ILC3s only represent a minor population. In patients with newly diagnosed or active CD (ACD) and refractory CD type 1 (RCD I), the frequency of SI NKp44+ ILCs is decreased, with restoration of NKp44+ ILC frequency observed in patients adhering to a gluten-free diet who show evidence of mucosal healing. Moreover, the frequency of SI NKp44- ILCs is increased in ACD and RCD I patients and correlates with the severity of villous atrophy and epithelial damage, as assessed by serum levels of fatty acid binding protein 2 (FABP2). We show that the ILC alterations in CD represent a phenotypic shift of cytotoxic ILC1s rather than an increase in helper ILC1s or transdifferentiation of ILC1s to ILC3s, and activation-induced loss of NKp44 by cytotoxic ILC1s is associated with increased interferon (IFN)-γ expression and release of lytic granules. These findings suggest that intra-epithelial NKp44- CD127- cytotoxic ILC1s may contribute to mucosal damage in CD.

Preferential intracellular pH regulation is a common trait amongst fishes exposed to high environmental CO2.

Acute (<96 h) exposure to elevated environmental CO2 (hypercarbia) induces a pH disturbance in fishes that is often compensated by concurrent recovery of intracellular and extracellular pH (pHi and pHe, respectively; coupled pH regulation). However, coupled pH regulation may be limited at CO2 partial pressure (PCO2 ) tensions far below levels that some fishes naturally encounter. Previously, four hypercarbia-tolerant fishes had been shown to completely and rapidly regulate heart, brain, liver and white muscle pHi during acute exposure to >4 kPa PCO2  (preferential pHi regulation) before pHe compensation was observed. Here, we test the hypothesis that preferential pHi regulation is a widespread strategy of acid-base regulation among fish by measuring pHi regulation in 10 different fish species that are broadly phylogenetically separated, spanning six orders, eight families and 10 genera. Contrary to previous views, we show that preferential pHi regulation is the most common strategy for acid-base regulation within these fishes during exposure to severe acute hypercarbia and that this strategy is associated with increased hypercarbia tolerance. This suggests that preferential pHi regulation may confer tolerance to the respiratory acidosis associated with hypercarbia, and we propose that it is an exaptation that facilitated key evolutionary transitions in vertebrate evolution, such as the evolution of air breathing.

Functional support for a novel mechanism that enhances tissue oxygen extraction in a teleost fish.

A successful spawning migration in salmon depends on their athletic ability, and thus on efficient cardiovascular oxygen (O2) transport. Most teleost fishes have highly pH-sensitive haemoglobins (Hb) that can release large amounts of O2 when the blood is acidified at the tissues. We hypothesized that plasma-accessible carbonic anhydrase (paCA; the enzyme that catalyses proton production from CO2) is required to acidify the blood at the tissues and promote tissue O2 extraction. Previous studies have reported an elevated tissue O2 extraction in hypoxia-acclimated teleosts that may also be facilitated by paCA. Thus, to create experimental contrasts in tissue O2 extraction, Atlantic salmon were acclimated to normoxia or hypoxia (40% air saturation for more than six weeks), and the role of paCA in enhancing tissue O2 extraction was tested by inhibiting paCA at rest and during submaximal exercise. Our results show that: (i) in both acclimation groups, the inhibition of paCA increased cardiac output by one-third, indicating a role of paCA in promoting tissue O2 extraction during exercise, recovery and at rest; (ii) the recruitment of paCA was plastic and increased following hypoxic acclimation; and (iii) maximal exercise performance in salmon, and thus a successful spawning migration, may not be possible without paCA.

Effect of oestrous synchrony between embryo donors and recipients, embryo quality and state on the pregnancy rate in beef cattle.

This study aimed to evaluate the effect of oestrous synchrony between donors and recipients and the embryo quality on the pregnancy rate in beef cow recipients. The experiment was performed over two years at an embryo transfer (ET) centre in Southern Brazil. Ninety Aberdeen Angus cows were subjected to superovulation (SOV) protocols, resulting in the recovery of 1,048 transferable embryos. Eleven groups were formed with intervals of 6 hr, from -30 to +30 hr, with respect to recipient versus donor oestrous detection. Evaluation of embryo quality was according to the IETS guidelines. The overall pregnancy rate was 52%. Effects related to donor and recipient oestrous synchronization on pregnancy rate were observed (p = .01), ranging from 36% to 50%. The embryo quality rate affected the pregnancy rate, where Grade I resulted in 57% and Grade III in 43% of pregnancy (p < .001). The embryonic state (frozen or fresh) showed no (p > .05) effect on pregnancy rate: 53% for fresh embryos and 44% for frozen embryos. The odds ratio for explanatory variables causing pregnancy indicated that Grade III embryos had 31% less chance of conception compared to Grade I. Thus, oestrous synchrony between donor and recipient, considering ±30 hr apart, can affect the pregnancy rate along with embryo quality.

The effect of substrate rearing on growth, aerobic scope and physiology of larval white sturgeon Acipenser transmontanus.

The effect of substratum on growth and metabolic rate was assessed in larval white sturgeon Acipenser transmontanus. Yolk-sac larvae (YSL) were reared in bare tanks or tanks with gravel as substratum from hatch until approximately 16 days post hatch (dph). The effect of an artificial substratum was also evaluated on growth alone. Substratum had a significant effect on mass, with larvae reared in gravel and artificial substrata being larger than those reared without substratum. Routine metabolic rates were significantly lower and relative aerobic scope (the difference between maximum and routine metabolic rate) was significantly higher for YSL and feeding larvae (FL) reared in gravel relative to those reared in bare tanks, particularly before fish started feeding exogenously. Furthermore, gravel-reared larvae had higher whole-body glycogen concentrations relative to bare-tank-reared larvae. Routine factorial scope (maximum metabolic rate divided by routine metabolic rate) was relatively low in all treatments (< 1·7) indicating a limited ability to elevate metabolic rate above routine early in development and mass exponents for metabolic rate exceeded 1. Taken together, these data indicate that YSL reared without substratum may divert more of their energy to non-growth related processes impairing growth. This finding underscores the importance of adequate rearing substratum for growth of A. transmontanus and may provide support for habitat restoration and alternative hatchery rearing methods associated with sturgeon conservation.

A unique mode of tissue oxygenation and the adaptive radiation of teleost fishes.

Teleost fishes constitute 95% of extant aquatic vertebrates, and we suggest that this is related in part to their unique mode of tissue oxygenation. We propose the following sequence of events in the evolution of their oxygen delivery system. First, loss of plasma-accessible carbonic anhydrase (CA) in the gill and venous circulations slowed the Jacobs-Stewart cycle and the transfer of acid between the plasma and the red blood cells (RBCs). This ameliorated the effects of a generalised acidosis (associated with an increased capacity for burst swimming) on haemoglobin (Hb)-O2 binding. Because RBC pH was uncoupled from plasma pH, the importance of Hb as a buffer was reduced. The decrease in buffering was mediated by a reduction in the number of histidine residues on the Hb molecule and resulted in enhanced coupling of O2 and CO2 transfer through the RBCs. In the absence of plasma CA, nearly all plasma bicarbonate ultimately dehydrated to CO2 occurred via the RBCs, and chloride/bicarbonate exchange was the rate-limiting step in CO2 excretion. This pattern of CO2 excretion across the gills resulted in disequilibrium states for CO2 hydration/dehydration reactions and thus elevated arterial and venous plasma bicarbonate levels. Plasma-accessible CA embedded in arterial endothelia was retained, which eliminated the localized bicarbonate disequilibrium forming CO2 that then moved into the RBCs. Consequently, RBC pH decreased which, in conjunction with pH-sensitive Bohr/Root Hbs, elevated arterial oxygen tensions and thus enhanced tissue oxygenation. Counter-current arrangement of capillaries (retia) at the eye and later the swim bladder evolved along with the gas gland at the swim bladder. Both arrangements enhanced and magnified CO2 and acid production and, therefore, oxygen secretion to those specialised tissues. The evolution of ß-adrenergically stimulated RBC Na(+)/H(+) exchange protected gill O2 uptake during stress and further augmented plasma disequilibrium states for CO2 hydration/dehydration. Finally, RBC organophosphates (e.g. NTP) could be reduced during hypoxia to further increase Hb-O2 affinity without compromising tissue O2 delivery because high-affinity Hbs could still adequately deliver O2 to the tissues via Bohr/Root shifts. We suggest that the evolution of this unique mode of tissue O2 transfer evolved in the Triassic/Jurassic Period, when O2 levels were low, ultimately giving rise to the most extensive adaptive radiation of extant vertebrates, the teleost fishes.

Clinical value and safety of liver biopsies in patients transplanted for hepatitis C virus-related end-stage liver disease.

BACKGROUND: Hepatitis C is the leading indication for liver transplantation. Differentiation between recurrent graft hepatitis C (RGH-C) and graft rejection (GR) is challenging. Liver biopsy is standard to diagnose both conditions; however, little information is available regarding this procedure in hepatitis C virus (HCV)-infected liver transplant recipients. METHODS: Liver biopsies (n = 211) from all consecutive patients (n = 138) transplanted for hepatitis C at Hannover Medical School between January 2000 and October 2011 were screened, and a final cohort of 96 patients with 196 biopsies was included. Indications, histopathological findings, and biopsy-related complications were documented. Modifications in the treatment based on the biopsy result and the biochemical outcome were analyzed. RESULTS: Most biopsies (196/211, 93%) were representative. Five patients (2.5%) developed non-fatal biopsy-related complications. Biopsy results were GR (35%), RGH-C (31%), and other diagnoses (34%). GR was independently associated with lower albumin (P = 0.025) and higher bilirubin levels (P = 0.011). Treatment was modified based on the biopsy result in 25% of cases. Alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), and bilirubin levels improved in 41%, 25%, and 31% of cases 4 weeks post biopsy respectively. ALT improvements were more significant in patients with GR than in those with RGH-C. CONCLUSION: Liver biopsy in HCV-infected liver transplant recipients is safe and representative in >90% of cases. GR is independently associated with lower albumin and higher bilirubin levels.

Acid-base and ion balance in fishes with bimodal respiration.

The evolution of air breathing during the Devonian provided early fishes with bimodal respiration with a stable O2 supply from air. This was, however, probably associated with challenges and trade-offs in terms of acid-base balance and ionoregulation due to reduced gill:water interaction and changes in gill morphology associated with air breathing. While many aspects of acid-base and ionoregulation in air-breathing fishes are similar to water breathers, the specific cellular and molecular mechanisms involved remain largely unstudied. In general, reduced ionic permeability appears to be an important adaptation in the few bimodal fishes investigated but it is not known if this is a general characteristic. The kidney appears to play an important role in minimizing ion loss to the freshwater environment in the few species investigated, and while ion uptake across the gut is probably important, it has been largely unexplored. In general, air breathing in facultative air-breathing fishes is associated with an acid-base disturbance, resulting in an increased partial pressure of arterial CO2 and a reduction in extracellular pH (pHE ); however, several fishes appear to be capable of tightly regulating tissue intracellular pH (pHI ), despite a large sustained reduction in pHE , a trait termed preferential pHI regulation. Further studies are needed to determine whether preferential pHI regulation is a general trait among bimodal fishes and if this confers reduced sensitivity to acid-base disturbances, including those induced by hypercarbia, exhaustive exercise and hypoxia or anoxia. Additionally, elucidating the cellular and molecular mechanisms may yield insight into whether preferential pHI regulation is a trait ultimately associated with the early evolution of air breathing in vertebrates.

Early life stage salinity tolerance of wild and hatchery-reared juvenile pink salmon Oncorhynchus gorbuscha.

Salinity tolerance in wild (Glendale) and hatchery (Quinsam) pink salmon Oncorhynchus gorbuscha (average mass 0·2 g) was assessed by measuring whole body [Na(+)] and [Cl⁻] after 24 or 72 h exposures to fresh water (FW) and 33, 66 or 100% sea water (SW). Gill Na(+), K(+)-ATPase activity was measured following exposure to FW and 100% SW and increased significantly in both populations after a 24 h exposure to 100% SW. Whole body [Na(+)] and whole body [Cl⁻] increased significantly in both populations after 24 h in 33, 66 and 100% SW, where whole body [Cl⁻] differed significantly between Quinsam and Glendale populations. Extending the seawater exposure to 72 h resulted in no further increases in whole body [Na(+)] and whole body [Cl⁻] at any salinity, but there was more variability among the responses of the two populations. Per cent whole body water (c. 81%) was maintained in all groups of fish regardless of salinity exposure or population, indicating that the increase in whole body ion levels may have been related to maintaining water balance as no mortality was observed in this study. Thus, both wild and hatchery juvenile O. gorbuscha tolerated abrupt salinity changes, which triggered an increase in gill Na(+), K(+)-ATPase within 24 h. These results are discussed in terms of the preparedness of emerging O. gorbuscha for the marine phase of their life cycle.

Phylogeography and conservation genetics of Lake Qinghai scaleless carp Gymnocypris przewalskii.

The objective of this study was to examine the spatial genetic relationships of the Lake Qinghai scaleless carp Gymnocypris przewalskii within the Lake Qinghai system, determining whether genetic evidence supports the current taxonomy of Gymnocypris przewalskii przewalskii and Gymnocypris przewalskii ganzihonensis and whether Gymnocypris przewalskii przewalskii are returning to their natal rivers to spawn. Comparison of mitochondrial (control region) variation (42 haplotypes in 203 fish) of G. przewalskii with the postulated ancestral species found in the Yellow River, Gymnocypris eckloni (10 haplotypes in 23 fish), indicated no haplotype sharing, but incomplete lineage sorting. Consistent with the sub-species status, an AMOVA indicated that the Ganzi River population was significantly different from all other river populations (F(ST) = 0·1671, P < 0·001). No genetic structure was found among the other rivers in the Lake Qinghai catchment. An AMOVA of amplified fragment length polymorphism (AFLP) loci, however, revealed significant genetic differences between most spawning populations (F(ST) = 0·0721, P < 0·001). Both mitochondrial and AFLP data found significant differences among G. p. przewalskii, G. p. ganzihonensis and G. eckloni (F(ST) values of 0·1959 and 0·1431, respectively, P < 0·001). Consistent with the incomplete lineage sorting, Structure analysis of AFLP loci showed evidence of five clusters. One cluster is shared among all sample locations, one is unique to G. p. ganzihonensis and G. eckloni, and the others are mostly found in G. p. przewalskii. Genetic evidence therefore supports the current taxonomy, including the sub-species status of G. p. ganzihonensis, and is consistent with natal homing of most Lake Qinghai populations. These findings have significant implications for the conservation and management of this unique and threatened species. The evidence suggests that G. p. przewalskii should be treated as a single population for conservation purposes. Exchangeability of the populations, however, should not be used to promote homogenization of fish spawning in the different rivers. As some degree of genetic divergence was detected in this study, it is recommended that the spawning groups be treated as separate management units.

A validation of intracellular pH measurements in fish exposed to hypercarbia: the effect of duration of tissue storage and efficacy of the metabolic inhibitor tissue homogenate method.

This study assessed the effect of tissue storage duration and accuracy of the metabolic inhibitor tissue homogenate (MITH) method on intracellular pH (pHi) values of tissues of white sturgeon Acipenser transmontanus during hypercarbia. No effect of storage in liquid nitrogen of up to 30 days was observed and MITH appears appropriate for measurement of pH in fish exposed to up to 10% CO2 (10000 Pa pCO2).

Swimming performance and associated ionic disturbance of juvenile pink salmon Oncorhynchus gorbuscha determined using different acceleration profiles.

Swimming performance was assessed in juvenile pink salmon Oncorhynchus gorbuscha (body mass<5.0 g) using five different protocols: four constant acceleration tests each with a different acceleration profile (rates of 0.005, 0.011, 0.021 and 0.053 cm s(-2)) and a repeated ramped-critical swimming speed test. Regardless of the swim protocol, the final swimming speeds did not differ significantly (P>0.05) among swim tests and ranged from 4.54 to 5.20 body lengths s(-1). This result supports the hypothesis that at an early life stage, O. gorbuscha display the same fatigue speeds independent of the swimming test utilized. Whole body and plasma [Na+] and [Cl-] measured at the conclusion of these tests were significantly elevated when compared with control values (P<0.05) and appear to be predominantly associated with dehydration rather than net ion gain. Given this finding for a small salmonid, estimates of swim performance can be accurately measured with acceleration tests lasting<10 min, allowing a more rapid processing than is possible with a longer critical swim speed test.

Limits of grape byproduct inclusion in diets for lambs: Zinc supplementation to prevent copper poisoning.

The aims of the current study were to assess the inclusion levels of grape byproduct replacing jiggs hay in lambs diets and to evaluate signs of copper poisoning. Thirty-four Texel and Corriedale crossbred female lambs were used in a randomized block experimental design. The treatments comprised four levels of grape byproduct (0; 100; 200 and 300 g/kg DM) in replacement of jiggs hay. The diets were adjusted to the same ZnCu ratio (6:1) of the basal diet. Grape byproduct consumption at up to 30%, led to similar weight gain in the different treatments (P = .92), which was suitable for growing lambs. Grape byproduct in the diet had linear effect on GGT (P < .001) and AST (P < .0001) enzymes as well as on total bilirubin (P = .05). In addition, the highest grape byproduct addition showed the highest consumption of hay (P < .01). Hay replacement by grape byproduct at up to 300 g/kg in the DM was satisfactory to weight gain and did not negatively affect feed intake and weight gain of growing lambs. Maintaining zinc:copper ratio in sheep diets is not effective in preventing liver damage caused by increased dietary copper concentrations over a period of 70 days.

Genetic analysis of age at first calving, accumulated productivity, stayability and mature weight of Nellore females.

The female reproductive performance, productivity and size are strongly associated with production efficiency of herds raised in a tropical environment. The age at first calving (AFC), accumulated productivity (AP), stayability (STAY) and mature weight (MW) could be used as indicators of these traits. In this study, the genetic parameters and correlations between AFC, AP, STAY and MW measured in Nellore females were estimated, in order to provide support for the beef cattle evaluation programs. In addition, the genetic changes for these traits were obtained. The (co)variance components were estimated by Gibbs sampling by four-trait multivariate analysis, using a threshold animal model for STAY and linear animal model for the other traits (AFC, AP and MW). Heritability of AFC, AP and STAY showed low values, with posterior means of 0.13 ± 0.02, 0.14 ± 0.01 and 0.19 ± 0.03, respectively. On the other hand, for MW were estimated mean heritability of 0.44 ± 0.03 and repeatability of 0.77 ± 0.03, demonstrating the importance of genetic and permanent environmental effects for the expression of beef cows' size. The AFC showed null genetic correlation with AP (-0.06 ± 0.12) and MW (0.01 ± 0.09) and low and negative with STAY (-0.15 ± 0.11). The AP showed high genetic correlation with STAY (0.86 ± 0.03) and weak with MW (0.23 ± 0.09). Positive and moderate genetic association was estimated between STAY and MW (0.66 ± 0.05). Annual direct genetic trends of 0.19 kg, 0.30 units and 0.10 kg were estimated for AP, STAY and MW, respectively, and were significant (P < 0.05) for STAY and MW. For AFC, negative and favorable annual genetic change was estimated (-0.08 months, P < 0.05). In this population, the selection of heifers for an early reproductive age should have little influence, however favorable, in the time that the cows remain in the herd. The use of AP as a selection criterion should result in smaller changes in the females' mature weight when compared to selection based on STAY.

Effect of mature size and body condition of Nelore females on the reproductive performance.

The size and body condition of cows can affect their reproductive efficiency. However, few studies reported genetic correlations between these traits in beef cattle. Thus, we estimated the genetic parameters and correlations between weight (MW), height (MH) and body condition score (BCS) of cows and reproductive traits (SC: scrotal circumference, AFC: age at first calving, GL: gestation length, DC: days to calving, and CI: calving interval) in Nelore animals. In addition, it has also obtained direct and correlated responses aiming at determining whether changes in cow size and body condition may affect the herd reproductive performance. A series of two-trait Bayesian analyzes were performed including MW, MH or BCS with each of the reproductive traits. The heritability estimated for MW, MH and BCS were 0.46 ±â€¯0.02, 0.35 ±â€¯0.01 and 0.17 ±â€¯0.02, indicating an involvement of additive gene action mainly in cows' size determination. For the reproductive traits of females, heritability ranged from 0.05 ±â€¯0.00 for CI to 0.18 ±â€¯0.01 for GL, and was 0.37 ±â€¯0.01 for SC. Low repeatability were estimates for GL (0.19 ±â€¯0.00), DC (0.19 ±â€¯0.00) and CI (0.05 ±â€¯0.00). The MW was positive correlated with AFC (0.23 ±â€¯0.08), CI (0.25 ±â€¯0.15) and, with lower magnitude, of GL (0.14 ±â€¯0.03). Null genetic correlations were obtained between MW with SC (0.03 ±â€¯0.03) and DC (-0.01 ±â€¯0.04). The MH showed positive and low genetic association with all female reproductive traits, but negative with SC (-0.08 ±â€¯0.03). Negative and favorable genetic correlations were estimated between BCS and females reproductive traits, but unfavorable with SC (-0.13 ±â€¯0.06). In summary, the negative impact of increase the size of Nelore females on their reproductive performance is expected to be small in tropical regions. The use of sires with high genetic breeding values for SC should result in slight reduction of BCS of cows, but no effective genetic response in female size is expected. Selection based on BCS should promote little improvement in reproductive efficiency of cows.

Intraspecific variation and plasticity in mitochondrial oxygen binding affinity as a response to environmental temperature.

Mitochondrial function has been suggested to underlie constraints on whole-organism aerobic performance and associated hypoxia and thermal tolerance limits, but most studies have focused on measures of maximum mitochondrial capacity. Here we investigated whether variation in mitochondrial oxygen kinetics could contribute to local adaptation and plasticity in response to temperature using two subspecies of the Atlantic killifish (Fundulus heteroclitus) acclimated to a range of temperatures (5, 15, and 33 °C). The southern subspecies of F. heteroclitus, which has superior thermal and hypoxia tolerances compared to the northern subspecies, exhibited lower mitochondrial O2 P50 (higher O2 affinity). Acclimation to thermal extremes (5 or 33 °C) altered mitochondrial O2 P50 in both subspecies consistent with the effects of thermal acclimation on whole-organism thermal tolerance limits. We also examined differences between subspecies and thermal acclimation effects on whole-blood Hb O2-P50 to assess whether variation in oxygen delivery is involved in these responses. In contrast to the clear differences between subspecies in mitochondrial O2-P50 there were no differences in whole-blood Hb-O2 P50 between subspecies. Taken together these findings support a general role for mitochondrial oxygen kinetics in differentiating whole-organism aerobic performance and thus in influencing species responses to environmental change.

Noncancer deaths in white adult cancer patients.

BACKGROUND: The cancer-specific death rate is a commonly used indicator in the assessment of progress against cancer. However, since the cause of death is often not substantiated and complete medical information is lacking, the validity of cancer-specific mortality rates is being questioned. PURPOSE: We investigated the validity of the cancer-specific death rate by examining noncancer deaths of cancer patients in a large patient population. METHODS: Data were obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program on cancer patients diagnosed between 1973 and 1987, with follow-up complete through December 1987. The SEER database consists of 1.2 million records from nine population-based registries covering nine geographic regions of the United States. Rates of noncancer deaths in the U.S. population were obtained from the National Center for Health Statistics. Cancer mortality rates were subtracted from overall mortality rates to obtain noncancer death rates by sex and the 5-year age group for each calendar year. Excluded from the study were patients of races other than White and those diagnosed at age 85 years or more due to absence of noncancer death rate comparisons. Also excluded were cancer cases discovered at autopsy and in persons less than 20 years of age. The statistical analysis employed a log-linear model. RESULTS: The ratio of patient-to-general-population noncancer death rates, as calculated by dividing the number of patient noncancer deaths per year by the number found in the matched U.S. population data and referred to as the noncancer relative hazard, is considered significant with values greater than 1 for those with all cancers combined and for the common solid tumors examined. Of the 12 leading causes of death other than cancer in the patient population, the most common causes were circulatory and respiratory failures. The noncancer relative risk of death decreased rapidly after diagnosis and also decreased with the patient's age at diagnosis. It increased slightly with the calendar year of diagnosis. CONCLUSIONS: Because more noncancer deaths occurred shortly after diagnosis, it appears that this excess was caused by treatment of the cancer. Generally, cancer-specific death rates underestimate the mortality associated with a diagnosis of cancer. Therefore, because the degree of underestimation changes with time, an examination solely of cancer-caused mortality in assessing progress against the disease is incomplete.

Assessing changes in the impact of cancer on population survival without considering cause of death.

BACKGROUND: We have previously argued against the calculation of cancer-specific death rates as philosophically undefined and biased. Deaths attributed to cancer during a particular year occur in patients diagnosed during an unknown distribution of past times, so cancer-specific death rates cannot be used to assess changes in the impact of cancer on survival of the population at specific periods of diagnosis. PURPOSE: Our goal was to develop and analyze three measures of the impact of cancer on population survival that do not use the attributed cause of death: 1) the age-adjusted proportion of the population diagnosed with cancer in a particular year and projected to be dead of any cause by a particular age; 2) the same measure corrected for population mortality; and 3) the expected years of life lost to a 20-year-old individual because of the possibility of a diagnosis of cancer. METHODS: Data on all adults diagnosed with any cancer during the period from January 1973 through December 1990 were obtained from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. The measures were calculated separately for various combined sex and race groups. Three 2-year diagnosis periods spaced 5 years apart were considered: 1975-1976, 1980-1981, and 1985-1986. A statistical model was used to extrapolate survival beyond observation; the same model was used for patients diagnosed in the three time periods to minimize the effect of possible model misspecification on changes. RESULTS: Cancer incidence increased for three of the four sex-race groups; age-adjusted changes from 1975 through 1976 to 1985 through 1986 were +11.5% for white men, +6.9% for white women, +15.1% for black men, and -9.2% for black women. Human immunodeficiency virus (HIV)-related cancers were responsible for an increased cancer incidence at early ages in white men in the latest time period studied. There was a decrease in the incidence of gynecologic cancers at early ages; the decrease was greater among black women (-55.1%) than among white women (-39.3%). Age- and incidence-adjusted 5-year survival increased by 17.9% for white men, 2.3% for white women, and 7.4% for black men and decreased by 14.1% for black women. When the data from 1985 through 1986 were compared with those from 1975 through 1976, the expected number of years lost to a 20-year-old individual because of cancer changed as follows for the various sex-race groups: +1.4% for white men (-4.0% if HIV-related cancers were not included in the calculation), +2.1% for white women, +12.2% for black men, and +8.8% for black women. CONCLUSIONS: For white men and women, there has been an increase in both the incidence of and survival following the diagnosis of cancer; the two effects nearly cancel in our measures. The experience of black men and women has worsened because of increasing incidence or decreased survival.

Different doses of equine chorionic gonadotropin on ovarian follicular growth and pregnancy rate of suckled Bos taurus beef cows subjected to timed artificial insemination protocol.

This study evaluated the effect of different doses of eCG (control, 300 or 400 IU) administered at progesterone (P4) device removal in suckled Bos taurus beef cows undergoing a timed artificial insemination (TAI) protocol. A total of 966 cows received a P4 insert and 2.0 mg intramuscular estradiol benzoate at the onset of the synchronization. After 9 days, P4 insert was removed, and 12.5 mg of dinoprost tromethamine and 1 mg of estradiol cypionate were administered, followed by TAI 48 hours later. Then, the cows received one of three treatments as follows: control (n = 323), 300 (n = 326), or 400 IU of eCG (n = 317). A subset (n = 435) of cows in anestrus had their ovaries evaluated using ultrasound at the time of P4 removal and at TAI. Data were analyzed by orthogonal contrasts (C): C1 (eCG effect) and C2 (eCG dose effect). Estrous occurrence (control = 53.7%, 300 IU = 70.6%, and 400 IU = 77.0%) and pregnancy per artificial insemination (control = 29.7%, 300 IU = 44.8%, and 400 IU = 47.6%) were improved by eCG treatment (C1; P = 0.0004 and P < 0.0001, respectively). Furthermore, the cows receiving eCG presented larger follicles at TAI (control = 13.5 ± 0.3 mm, 300 IU = 14.0 ± 0.2 mm, and 400 IU = 15.1 ± 0.3 mm; P < 0.0001; C1). However, there was no effect of eCG dose on any response variables studied (C2; P > 0.15). In conclusion, the eCG treatment administered at the time of P4 removal increased the occurrence of estrus, the larger follicles at TAI, and pregnancy per artificial insemination of suckled B taurus beef cows. Despite the greater occurrence of estrus in noncyclic cows receiving 400 IU of eCG, both eCG doses (300 and 400 IU) were equally efficient to improve pregnancy to artificial insemination.