Rapid capping in alpha-spectrin-deficient MEL cells from mice afflicted with hereditary hemolytic anemia.

A spectrin-based membrane skeleton is important for the stability and organization of the erythrocyte. To study the role of spectrin in cells that possess complex cytoskeletons, we have generated alpha-spectrin-deficient erythroleukemia cell lines from sph/sph mice. These cells contain beta-spectrin, but lack alpha-spectrin as determined by immunoblot and Northern blot analyses. The effects of alpha-spectrin deficiency are apparent in the cells' irregular shape and fragility in culture. Capping of membrane glycoproteins by fluorescent lectin or antibodies occurs more rapidly in sph/sph than in wild-type erythroleukemia cells, and the caps appear more concentrated. The data support the idea that spectrin plays an important role in organizing membrane structure and limiting the lateral mobility of integral membrane glycoproteins in cells other than mature erythrocytes.

Associations between blood gastrin, ghrelin, leptin, pepsinogen and Ostertagia ostertagi antibody concentrations and voluntary feed intake in calves exposed to a trickle infection with O. ostertagi.

Twenty-five, castrated male Holstein-cross calves, between 4 and 5 months of age, weighing 156.5+/-12.2 kg and reared under conditions designed to minimise the risk of parasitic infection, were allocated to one of the five treatment groups on the basis of initial bodyweight. The groups were (1) ad libitum (ad lib) fed controls (ALC); (2) ad lib fed infected (INF) and treated with topical eprinomectin on Day 56; (3) controls pair-fed with the INF group (PFC); (4) ad lib fed controls treated with eprinomectin on Days 0 and 56 (E-ALC) and (5) ad lib fed, infected and treated with eprinomectin on Days 0 and 56 (E-INF). Infection comprised a trickle infection with the equivalent of 10,000 larvae of Ostertagia ostertagi per day from Day 0 to Day 56 and the study concluded on Day 77. Parameters measured throughout the study included: liveweight, feed intake, faecal egg counts; plasma pepsinogen, gastrin, ghrelin and leptin; plasma antibodies to adult O. ostertagi. No significant differences in feed intake or liveweight gain were observed between any of the different groups, a finding thought to result from the high quality of feed offered. Significant differences between the INF and control groups however were observed in faecal egg counts, plasma pepsinogen, gastrin and O. ostertagi antibodies, which were all elevated, and leptin, which was reduced. Values of these parameters for the E-INF group were intermediate between the INF and ALC groups. Plasma ghrelin showed no association with either feed intake or parasitism. Further studies are needed to fully elucidate the roles of various biochemical and neuroendocrine mediators for inappetence in ruminants with parasitic gastroenteritis.

Angiostrongylus vasorum and Eucoleus aerophilus in foxes (Vulpes vulpes) in Great Britain.

The nematode parasite Angiostrongylus vasorum is a source of increasing concern in several parts of the world, where it causes significant disease in dogs. Wild canids, especially foxes, are likely to have a role in the epidemiology of canine infection, and the parasite could also affect fox health and population dynamics. The heart and pulmonary vasculature of 546 foxes culled mostly by gamekeepers in Great Britain in 2005-2006 were examined by dissection and a modified flushing technique. Forty foxes were found to be infected, giving an overall prevalence in the UK fox population of 7.3% (5.3-9.9). Prevalence varied widely between regions, from 0% (0-3) in Scotland and northern England to 23% (16-32) in south-east England. This closely matches the perceived incidence of disease in dogs, which is commonly diagnosed in the south-east but rarely in the north. In the Midlands, where disease has recently appeared in dogs, prevalence in foxes was 4.8% (2-11). Close geographical overlap of parasite distribution in foxes and dogs does not necessarily indicate an important wildlife reservoir of infection, but does suggest that A. vasorum might be spreading northwards. The hearts of infected foxes had thicker right ventricles than those of uninfected foxes, suggesting that the parasite could affect fox health and fitness. Burdens ranged from 1 to 59 adult nematodes. Sex, age and body condition were not significantly associated with infection. Eucoleus aerophilus and Crenosoma vulpis, nematode parasites of the respiratory system, were found in 213 and 11 foxes respectively, with slightly higher prevalence of E. aerophilus in the south and east. No specimens of the heartworm Dirofilaria immitis were found, giving an upper 95% confidence interval for prevalence of 0.84%.

Epidemiology of subclinical dairy cow nematode infections on five farms in England in 2002 and a comparison with results from 1978 to 1979.

A detailed study of the epidemiology of subclinical nematode infections in adult dairy cows was conducted on five well-managed English dairy farms during the 2002 grazing season. These same farms had also participated in a similar study in 1978-1979 and thus provided a unique opportunity to compare the epidemiological findings after an interval of over two decades. Common factors, including the prevalence of infection, faecal worm egg output, pasture larval count and nematode genera present, and estimated daily larval intake at pasture, were compared between the two studies. Subclinical roundworm burdens, as judged by faecal egg counts, were widespread in dairy cows in 2002, but the prevalence of animals with patent infections and the magnitude of the worm egg output were significantly lower than in 1978-1979. Both the prevalence of infection and mean faecal worm egg output exhibited a marked seasonal peak during the summer months in 2002. Pasture larval numbers were, however, nearly three times higher in 2002 with Ostertagia dominating the nematode genera to which cows were exposed at pasture in both surveys. Factors considered likely to account for differences in parasite epidemiology include the marked increase in herd productivity over the intervening period, the increased proportion of Holstein genetics with the consequent increase in milk yield and feed intake, changes in grassland management and increased stocking rate seen on the majority of farms.

Vagal and splanchnic afferent nerves are not essential for anorexia associated with abomasal parasitism in sheep.

Heavy burdens of the abomasal nematode, Ostertagia (Telodorsagia) circumcincta, in growing lambs result in a reduction in liveweight gain due largely to a drop in voluntary feed intake. The present study investigated: (1) the role of subdiaphragmatic vagal and non-vagal visceral afferent nerves in mediating a reduction in voluntary feed intake, using subdiaphragmatic vagal deafferentation (vagotomy) either alone or in combination with coeliac-superior mesenteric ganglionectomy (vagotomy and sympathectomy); and (2) the association between appetite, abomasal pH, selected blood values (amidated gastrin (G-17-amide), glycine-extended gastrin (G-17-Gly), pepsinogen and leptin) and worm burden, in sheep experimentally infected with 100,000 O. circumcincta infective larvae per os. Neither vagotomy alone nor vagotomy and sympathectomy in combination adversely affected the establishment or course of development of the parasite burden, when compared with a control group subject to sham surgery. Furthermore, neither surgical procedure prevented the drop in appetite seen 5-10 days post-infection, although combined vagotomy and sympathectomy did reduce voluntary feed intake prior to the start of the study. Ostertagia infection resulted in a significant increase in abomasal pH in all three groups, which was accompanied by an increase in blood G-17-amide and in G-17-Gly, the latter reported for the first time in parasitized ruminants. There were no significant differences in blood leptin, also reported for the first time in parasitized sheep, either between groups or in comparison with pre-infection levels, though weak negative correlations were established between blood leptin and appetite from day 5 to the end of the study in all three groups and a positive correlation with blood G-17-amide in the control group over the same period. These data suggest that neither intact subdiaphragmatic vagal afferent nerves or coeliac-superior mesenteric ganglion fibres, nor changes in circulating gastrin and leptin concentrations play a major role in mediating the hypophagic effects of O. circumcincta in parasitized sheep.

Field trial of a Caryospora species vaccine for controlling clinical coccidiosis in falcons.

A Caryospora species vaccine was prepared and used in an attempt to prevent infection and associated morbidity in falcons. A blind field trial was conducted, involving a vaccinated group of 20 birds and two control groups of seven and four birds, which were subsequently challenged with a live mixed-species vaccine. There was a statistically significant reduction in morbidity and shedding of oocysts in the vaccinated group compared with the control groups.

Prolactin-induced proliferation of the Nb2 T-lymphoma is associated with protein kinase-C-independent phosphorylation of stathmin.

Phosphorylation of stathmin, a 19-kDa protein found in many tissues, has been linked to cell differentiation and proliferation. This protein is present in lymphocytes, and both phosphorylation and expression of stathmin are regulated by lymphotropic agents. In this study an antibody specific for stathmin was used to examine phosphorylation in response to PRL. The results suggest that PRL stimulates stathmin phosphorylation in the Nb2 lymphoma and that phosphorylation correlates with PRL-induced cell proliferation. Stathmin expression does not change substantially as PRL-stimulated Nb2 cells move through the cell cycle and enter into the S-phase. Thus, stathmin phosphorylation, but not expression, is regulated by PRL. Activation of protein kinase-C (PKC) in Nb2 cells also induces phosphorylation of stathmin, but PKC does not appear to mediate phosphorylation in response to PRL. The pattern of phosphorylation in response to 12-O-tetradecanoylphorbol-13-acetate differs from that in response to PRL, and down-regulation of PKC does not inhibit PRL-induced phosphorylation or proliferation. In addition to stathmin, PRL increases phosphorylation of a group of stathmin-like proteins. Phosphorylation of these proteins also correlates well with PRL-induced proliferation. Taken together, the results suggest that phosphorylation of stathmin and stathmin-like proteins may mediate some actions of PRL in Nb2 cells. The results further suggest that activation of PKC is not an important early event in PRL-stimulated mitogenesis in Nb2 cells.

Identification of potential activators of proteinase-activated receptor-2.

In order to identify physiological activators of proteinase-activated receptor-2 (PAR-2), a peptide chloromethane inhibitor (biotinyl-Ser-Lys-Gly-Arg-CH2Cl) based on the cleavage site for activation of PAR-2 was synthesised and tested with 12 trypsin-like serine proteinases. The second-order rate constant (ki/Ki) for the formation of the covalent proteinase-inhibitor complex varied by 2 x 10(5)-fold between the proteinases. Biotinyl-Ser-Lys-Gly-Arg-CH2Cl reacted very rapidly with trypsin, acrosin from sperm and tryptase from mast cells: the ki/Ki values with these proteinases were greater than 10(5) M(-1) x s(-1). Thus, the specificity of these proteinases matched the sequence of the activation site of PAR-2 and it can be concluded that these proteinases are potential physiological activators of PAR-2.

Pain knowledge and attitudes of healthcare providers: practice characteristic differences.

OBJECTIVE: To evaluate the knowledge and attitudes of different healthcare professionals regarding pain issues such as addiction, the assessment of pain, scheduling, use of analgesics, and pediatric pain. Additionally, to determine whether differences exist based on hospital setting, years of service, clinical practice area, and country of origin. DESIGN: A total of 686 nurses, physicians, pharmacists, and medical/nursing students from three hospitals completed a 17-item survey evaluating knowledge and beliefs about pain. SETTING: The three hospital settings were a large city hospital, a private community hospital, and a state medical school-based hospital. RESULTS: The overall percentage "correct" score was only 56%. Physicians scored significantly higher, and pharmacists scored significantly lower than other groups. Nurses scored significantly less concordantly than physicians on 11 of the 17 items. Those identifying anesthesiology as their clinical practice area scored significantly higher than all other areas, whereas those practicing within medicine demonstrated significantly more "correct" scores than those in surgery. City hospital respondents scored significantly lower than professionals practicing in the other two hospitals; non-U.S. country of origin professionals scored significantly lower than U.S. country of origin healthcare professionals. There were no significant differences based on postgraduate years of practice. CONCLUSIONS: Significant knowledge deficits regarding currently accepted principles of pain management practice as well as beliefs that could interfere with optimal care, mandate a need for educational interventions. Significant differences by profession, clinical practice area, and hospital setting reflect populations to be targeted for interventions. Unwarranted fear of addiction is a misunderstood and important concept that needs to be addressed.

Co-exposure to gasoline vapor decreases benzene metabolism in Fischer-344 rats.

The metabolic interactions of benzene and gasoline vapor were investigated in male Fischer-344 rats. A closed chamber gas-uptake exposure system was used to obtain inhalation uptake curves for benzene alone and benzene in the presence of gasoline vapor. Exposure to benzene as a component of gasoline vapor resulted in a decrease of benzene metabolism. A physiologically based pharmacokinetic model of benzene metabolism was used to quantitatively determine the extent of the inhibitory effect of gasoline vapor on benzene metabolism. This observed inhibitory effect cannot be accounted for by the presence of toluene in gasoline vapor.

Pathophysiology of infection with Ostertagia ostertagi in cattle.

Infection with the abomasal nematode, Ostertagia ostertagi, is an important cause of impaired productivity in young cattle in temperate parts of the world. Such losses have been associated with marked changes in feed intake, gastrointestinal function, protein, energy and mineral metabolism, and in body composition. The reduction in feed intake is an important factor in the pathogenesis of infection and may account for a large part of the difference in weight gain between ad libitum fed control and infected calves. Despite the obvious importance of inappetance, only recently has an association been made between reduced intake, altered gut motility and elevated levels of certain gastrointestinal hormones, such as gastrin. It has been suggested that the elevated gastrin levels accompanying abomasal parasitism may impair reticulo-ruminal motility and slow down abomasal emptying, leading to a stasis of ingesta and a reduction in feed intake. The rise in blood gastrin levels may also be partly responsible for the marked hyperplasia of the fundic mucosa seen in abomasal infections. Pronounced changes in protein metabolism have also been associated with Ostertagia infection. Radioisotopic studies have demonstrated increased losses of albumin into the gastrointestinal tract which are accompanied by an increase in the rate of synthesis in the liver. Dietary protein breakdown in the abomasum is also likely to be impaired, although there is evidence of a compensatory increase in protein digestion in the lower gut of parasitised calves. Increased losses of albumin are not always accompanied by increases in faecal nitrogen, suggesting that albumin is broken down and recycled as ammonia. Radioisotopic studies in animals with intestinal nematode infections have demonstrated a marked reduction in muscle protein synthesis and an increase in protein synthesis in gastrointestinal tissue. Such changes in the balance of protein synthesis are likely to be brought about by alterations in the balance of certain metabolic hormones. Marked changes in energy metabolism also accompany Ostertagia infection. Parasitised calves exhibit a marked increase in non-esterified fatty acid levels, resulting from the mobilisation of adipose tissue, and a reduction in digestive efficiency of energy, probably associated with the increase in cycling of protein through the gastrointestinal tract and the compensatory increases in protein synthesis. Mineral metabolism may also be affected although relatively little work has been conducted in cattle. Changes in body composition reflect a reduction in deposition of muscle protein and fat, and an increase in bone content and water retention.

Pathophysiology of infection with gastrointestinal nematodes in domestic ruminants: recent developments.

Infection with gastrointestinal nematodes, particularly Ostertagia species in domestic ruminants, continues to represent an important cause of impaired productivity in temperate parts of the world. The mechanisms responsible for such losses include changes in feed intake, gastrointestinal function, protein, energy and mineral metabolism, and body composition, and were described in detail at the last Ostertagia Workshop (Fox, M.T. 1993. Pathophysiology of infection with Ostertagia ostertagi in cattle. Vet. Parasitol. 46, 143-158). Since then, research into the pathophysiology of infection has focused on three main areas: mechanisms of appetite depression; changes in gastrointestinal function; and alterations in protein metabolism. Studies on the mechanisms responsible for appetite depression in Ostertagia-infected cattle have continued to support a close association between impaired feed intake and elevated blood gastrin concentrations. Alternative explanations will have to be sought, however, to account for the drop in feed intake associated with intestinal parasitism in which blood gastrin levels normally remain unaltered. Such work in sheep, and more recently in laboratory animals, has shown that central satiety signals are associated with inappetance accompanying intestinal infections, rather than changes in peripheral peptide levels. Changes in gastrointestinal function have also attracted attention, particularly the mechanisms responsible for increases in certain gut secretions, notably pepsinogen and gastrin. Elegant experimental studies have established that the gradient in pepsinogen concentration between abomasal mucosa and local capillaries could alone account for the increase in blood concentrations seen in Type 1 ostertagiosis. Additional factors, such as increases in capillary permeability and in surface area, probably contribute to such responses in cases of Type 2 disease. The increase in blood gastrin concentrations that accompanies Ostertagia infections in cattle is associated with the concurrent rise in abomasal pH. However, in sheep, additional factors appear to contribute to the hypergastrinaemia which may occur independent of parasite-induced changes in gastric pH. Alterations in protein metabolism have been well documented in ruminants harbouring monospecific infections with either abomasal or intestinal nematodes. More recently, however, the effects of dual abomasal and intestinal infections have been investigated and demonstrated that the host is able to compensate for impaired abomasal digestion provided that the intestinal parasite burden does not occupy the main site of digestion and absorption in the latter organ. An alternative method of improving the host's protein balance, dietary supplementation, has been shown not only to improve productivity, but also to enhance the innate resistance of susceptible breeds of sheep to Haemonchus and to accelerate the development of immunity to Ostertagia in lambs.

Effects of Ostertagia ostertagi and omeprazole treatment on feed intake and gastrin-related responses in the calf.

Infection with the bovine abomasal nematode, Ostertagia ostertagi, results in a loss of acid-secreting parietal cells and an increase in gastric pH. The effects of an experimental infection with Ostertagia and/or daily treatment with omeprazole (OMP) at 2mgkg(-1) bodyweight for four consecutive days (experiment days 24-27, inclusive) on voluntary feed intake, blood and tissue gastrin concentrations, abomasal G-cell numbers, gastric pH, and blood cholecystokinin (CCK) and pepsinogen concentrations were investigated in the calf. Ostertagia-infected calves demonstrated a significant drop in feed intake between days 24 and 27 post-infection (38%; P<0.001) and in G-cell numbers (42%; P<0.05) and significant increases in abomasal pH (P<0.001), fundic mucosal weight (99%; P<0.01), and blood gastrin (P<0.05) and pepsinogen (P<0.0001). OMP treatment of worm-free animals resulted in a significant drop in intake between days 24 and 27 (30%; P<0.001) and in G-cell numbers (17%; P<0.05) and significant increases in abomasal pH (P<0.01) and blood gastrin (P<0.001). OMP treatment of Ostertagia-infected animals with an existing hypergastrinaemia had no effect on feed intake, abomasal pH, blood gastrin or pepsinogen or abomasal G-cell numbers. Blood CCK concentrations were also unaffected by either Ostertagia infection or OMP treatment. These data suggest that: (a) the depression in feed intake associated with OMP in worm-free calves was not due to a side effect of drug treatment; (b) inappetance in Ostertagia-infected animals is closely associated with the parasite-induced hypergastrinaemia; and (c) the elevation in abomasal pH was a major factor responsible for the elevated blood gastrin concentrations seen in parasitised and OMP-treated animals.

Comparative study of early-season prophylaxis using ivermectin with lungworm vaccination in the control of parasitic bronchitis and gastroenteritis in cattle.

Twenty-four first-season calves were randomly allocated to three similar groups (1-non-treated controls; 2 - vaccinated against lungworm; 3 - treated with ivermectin 21, 56 and 91 days after turnout) and set-stocked on separate pastures. Parasitic bronchitis became evident in the controls and signs of parasitic gastroenteritis were seen later in the vaccinates, but the ivermectin-treated calves remained healthy. After autumn housing, all were kept as a single group for the winter. The following summer, six of the ivermectin-treated animals and their matching vaccinates were grazed together, without further prophylaxis, along with six first-season calves. The latter displayed evidence of mild but debilitating pulmonary and gastrointestinal parasitic disease while both groups of yearlings remained healthy (with the exception of one diarrhoeic vaccinate). Thus, the immune status of the ivermectin-treated animals appeared to be comparable to that of the vaccinates. This conclusion was supported by parasitological observations and by artificial challenge at the end of the second grazing season.

Cold stress-induced modulation of cell immunity during acute Toxoplasma gondii infection in mice.

Infection with Toxoplasma gondii in the acute phase results in nonspecific suppression of immunologic function in mice and humans. The present study examined the effects of a physical stressor, i.e., cold stress (CS), on macrophage function (nitrite production, parasite survival) and splenic blastogenesis in the acute phase of murine T. gondii infection. In our stress paradigm, female BALB/c mice were placed in cold water (1 +/- 0.5 C), 5 min each day for 8 days. Nitrite production and parasite survival were measured in cultured peritoneal macrophages obtained from mice subjected to CS after in vivo activation with interferon-gamma/lipopolysaccharide (CS + ACT), and in vitro infection with T. gondii tachyzoites. Peritoneal macrophages from CS + ACT mice showed decreased nitrite production compared to control but activated cells (ACT). Spleen cell proliferation to in vitro stimulation with the mitogens concanavalin A (Con A) and anti-CD3, and Toxoplasma lysate antigen (TLA) was measured in splenocytes obtained from BALB/c mice during the acute phase of infection with T. gondii. Mice subjected to CS and infection (CS + INF) had maximum splenocyte proliferation on days 8 and 15 followed by a subsequent decline on day 28 postinoculation (PI). In contrast, infected mice not subjected to stress (INF) showed decreased splenocyte proliferation on days 8 and 15 followed by an increase on day 28 PI. The rate of mortality was decreased in the CS + INF compared to the INF group during acute infection. These results suggest that CS may alter the pathogenesis of T. gondii infection by modulating acute-phase responses, provoking a state of transient disequilibrium between the host and parasite.

Patterns of infection with Buxtonella sulcata in British cattle.

Buxtonella sulcata cysts were recovered from the faeces of adult cows on nine commercial dairy farms. Overall, 44.6 per cent of 496 animals sampled exhibited patent infections during the course of the study. Seasonal fluctuations in the prevalence of infection and cyst excretion rate were related to changes in diet and opportunities for transmission. An increase in prevalence of infection with lactation number was also demonstrated.

Twenty-four hour gastric pH monitoring and blood gastrin concentrations in fasted ponies.

Gastric pH varied widely among eight fasted ponies, of which seven exhibited discrete episodes of spontaneous alkalinisation (SA). SA occurred at all times of the study and no significant variation in the summary variables of pH (median pH, mean pH and percentage of readings exceeding pH 4.0) was noted among the periods 0 to eight, eight to 16 and 16 to 24 hours. The occurrence of SA has significant implications for the performance of acid secretory studies in the fasted pony. There was, however, no significant correlation between pH and plasma gastrin concentration measured using a commercially available radioimmunoassay kit validated for use in the horse. This implies a lack of dependency of the incidence of SA on plasma gastrin or, conversely, of plasma gastrin on the variable pH associated with SA.

Interactions between chemoprophylaxis and immunity to bovine parasitic gastroenteritis and bronchitis: pilot studies using an oxfendazole pulse release bolus.

In separate experiments, the immune status of six matched pairs of yearling heifers from a field trial in which both parasitic gastroenteritis and husk had occurred in control animals, was tested with a single massive challenge of either Dictyocaulus viviparus or Ostertagia ostertagi. The clinical responses of untreated controls and animals that had carried an oxfendazole pulse release intraruminal device (OPRB) were in all cases similar (with the exception of one lung-worm-challenged control that succumbed to a fulminating pulmonary hypersensitivity reaction), indicating that both groups possessed comparable degrees of protection. Faecal larval/egg-output data and serum gastrin levels, however, suggested that larger worm populations had established in the OPRB cattle.

Effect of omeprazole treatment on feed intake and blood gastrin and pepsinogen levels in the calf.

Previous work has shown blood gastrin levels to be elevated and appetite depressed in ostertagia-infected calves. A possible relationship between raised blood gastrin values and feed intake was investigated in worm-free animals using the human gastric acid secretion inhibitor, omeprazole. An initial dose-titration experiment established that administration of the drug by intravenous injection at 1.95 mg kg-1 (four times the recommended human dose rate) resulted in a marked (5.2-fold) increase in blood gastrin levels in the calf. Daily administration of omeprazole by intravenous injection at 2 mg kg-1 for four days in a subsequent experiment resulted in a significant depression in feed intake (up to 40.4 per cent) which was accompanied by a significant rise in blood gastrin levels (peak 940 pg ml-1; 6.5-fold increase over control values). It is suggested that such a rise in hormone levels would reduce reticuloruminal and abomasal motility, slow down the passage of ingesta and, in turn, lead to a reduction in appetite.

Blood gastrin and pepsinogen responses to subclinical infection with Ostertagia ostertagi in adult dairy cattle.

Blood gastrin and pepsinogen responses to a single infection with 100,000 Ostertagia ostertagi infective larvae in lactating dairy cows were investigated. None of the infected cows showed signs of clinical ostertagiasis, nor was there any difference in live weight gain, milk yield or faecal egg count between groups. Pepsinogen levels of the infected group were significantly elevated between days 3 and 24 after infection (peak 1041 mU tyrosine; day 14). In contrast, there was no significant difference in blood gastrin levels between infected and control animals suggesting that few adult worms had become established in the former group. These data are compared with the increases in both gastrin and pepsinogen levels recorded in susceptible calves exposed to the same level, pattern and strain of ostertagia infection in a previous experiment. It is suggested that gastrin assay may be of value in adult cattle for indicating when elevated pepsinogen levels are merely associated with a rise in larval intake and not with the establishment of large adult worm burdens.