IL-27: a double agent in the IL-6 family.

The cytokine interleukin (IL)-6 is a major therapeutic target for the treatment of various inflammatory and autoimmune diseases. While IL-6 receives considerable attention in studies of innate and adaptive immunity, the IL-6-related family member IL-27 is recognized increasingly for its effects on cellular proliferation, differentiation and leucocyte effector functions. Both cytokines activate responses in myeloid and stromal tissue cells, where they direct the transition from innate to adaptive immunity. However, they are identified frequently as lymphokines that control responses in T cells and B cells. In this regard, IL-27 often opposes the action of IL-6. Here, we will review the role of IL-6 and IL-27 in inflammation, with a particular focus on inflammatory arthritis, and discuss their importance in the diagnosis, stratification and treatment of autoimmune disease.

Exacerbated inflammatory arthritis in response to hyperactive gp130 signalling is independent of IL-17A.

OBJECTIVE: Interleukin (IL)-17A producing CD4 T-cells (TH-17 cells) are implicated in rheumatoid arthritis (RA). IL-6/STAT3 signalling drives TH-17 cell differentiation, and hyperactive gp130/STAT3 signalling in the gp130F/F mouse promotes exacerbated pathology. Conversely, STAT1-activating cytokines (eg, IL-27, IFN-γ) inhibit TH-17 commitment. Here, we evaluate the impact of STAT1 ablation on TH-17 cells during experimental arthritis and relate this to IL-17A-associated pathology. METHODS: Antigen-induced arthritis (AIA) was established in wild type (WT), gp130F/F mice displaying hyperactive gp130-mediated STAT signalling and the compound mutants gp130F/F:Stat1-/- and gp130F/F:Il17a-/- mice. Joint pathology and associated peripheral TH-17 responses were compared. RESULTS: Augmented gp130/STAT3 signalling enhanced TH-17 commitment in vitro and exacerbated joint pathology. Ablation of STAT1 in gp130F/F mice (gp130F/F:Stat1-/-) promoted the hyperexpansion of TH-17 cells in vitro and in vivo during AIA. Despite this heightened peripheral TH-17 cell response, disease severity and the number of joint-infiltrating T-cells were comparable with that of WT mice. Thus, gp130-mediated STAT1 activity within the inflamed synovium controls T-cell trafficking and retention. To determine the contribution of IL-17A, we generated gp130F/F:IL-17a-/- mice. Here, loss of IL-17A had no impact on arthritis severity. CONCLUSIONS: Exacerbated gp130/STAT-driven disease in AIA is associated with an increase in joint infiltrating T-cells but synovial pathology is IL-17A independent.

A successful clinical pilot registry of four radiation oncology practices in Africa and Ontario.

OBJECTIVE: Radiation Oncology practices can exhibit heterogeneities between and sometimes within institutions. Clinical registries with scope and detail could quantify consistency and distinctives that justify difference. Retrospective, isolated clinical audits are problematic, typically because not all data are captured in charts, while useful prospective clinical registries will have to be practical, efficient and accurate. We tested feasibility of a clinical registry at a critical time-point in the patient's clinical trajectory when treating physicians could have requisite data. DESIGN: This was a prospective and non-randomized observational study. Four centres used a 1-page form to acquire data during a 4-month period. Patients had curative breast, rectum or prostate cancers, or were palliative. Objectives were to demonstrate form completion and to delineate patterns of disease presentation and clinical practice. RESULTS: The 107 cases had 99% complete data, internally consistent within cases and centres. Similar practices were seen for 22 cases with curative rectal and prostate cancer, and 34 palliative cases, but of the 51 curative breast cancer cases those in Africa were with greater Stage, underwent more extensive surgery, were less likely to receive shorter radiation schedules, and were less exposed to Taxane-based chemotherapy regimens. CONCLUSIONS: This study demonstrates the feasibility for a simple clinical registry requiring minimal effort by participants. A real-time pan-African registry, operating continually or in regular waves, could provide important knowledge at little cost.

Design criteria for a printed tissue engineering construct: a mathematical homogenization approach.

Cartilage tissue repair procedures currently under development aim to create a construct in which patient-derived cells are seeded and expanded ex vivo before implantation back into the body. The key challenge is producing physiologically realistic constructs that mimic real tissue structure and function. One option with vast potential is to print strands of material in a 3D structure called a scaffold that imitates the real tissue structure; the strands are composed of gel seeded with cells and so provide a template for cartilaginous tissue growth. The scaffold is placed in the construct and pumped with nutrient-rich culture medium to supply nutrients to the cells and remove waste products, thus promoting tissue growth. In this paper we use asymptotic homogenization to determine the effective flow and transport properties of such a printed scaffold system. These properties are used to predict the distribution of nutrient/waste products through the construct, and to specify design criteria for the scaffold that will optimize the growth of functional tissue.

A review of the reliability and validity of the Edmonton Symptom Assessment System.

BACKGROUND: Systematic symptom reporting by patients and the use of questionnaires such as the Edmonton Symptom Assessment System (ESAS) have potential to improve clinical encounters and patient satisfaction. We review findings from published studies of the ESAS to guide use of the system and to focus research. METHODS: A systematic search for articles from 1991 through 2007 found thirty-nine peer-reviewed papers from 25 different institutions, thirty-three of which focused on patients with cancer. Observations, data, and statistics were collated according to relevance, reliability, validity, and responsiveness. RESULTS: Findings apply predominantly to symptomatic palliative patients with advanced cancer who were no longer receiving active oncologic therapies. Uncertainty about summarizing findings arises from frequent modification of the ESAS (altered items, scales, and time periods). Overall, reliability is established for daily administration. Scores are skewed, with a floor effect, but the relative order of symptoms by mean scores is similar across studies. Emotional symptoms are poorly captured by the depression and anxiety items. An equally weighted summation of scores may estimate a construct of "physical symptom distress," which in turn is related to performance status, palliative goals, quality of life, and well-being. CONCLUSIONS: The ESAS is reliable, but it has restricted validity, and its use requires a sound clinical process to help interpret scores and to give them an appropriate level of attention. Research priorities are to further develop the ESAS for assessing a greater number of important physical symptoms (and to target "physical symptom distress"), and to develop a similar instrument for emotional symptoms.

Trace elements, PCBs and organochlorine pesticides in New Zealand common dolphins (Delphinus sp.).

Trace elements, polychlorinated biphenyls (PCBs) and organochlorine (OC) pesticide levels were determined in tissues collected from stranded and bycaught common dolphins (Delphinus sp.) from New Zealand waters between 1999 and 2005. The concentrations of mercury (Hg), selenium (Se), chromium (Cr), zinc (Zn), nickel (Ni), cadmium (Cd), cobalt (Co), manganese (Mn), iron (Fe), copper (Cu), tin (Sn), lead (Pb), arsenic (As) and silver (Ag) were determined in blubber, liver and kidney tissue. PCBs (45 congeners) and a range of OC pesticides including dieldrin, hexachlorocyclohexane (HCH) and dichlorodiphenyltrichloroethane (DDT) and its metabolites DDE and DDD were determined in blubber samples. Cr and Ni were not detected in any of the samples and concentrations of Co, Sn and Pb were generally low. Concentrations of Hg ranged from 0.17 to 110 mg/kg wet weight. Organochlorine pesticides dieldrin, HCB, o,p'-DDT and p,p'-DDE were present at the highest concentrations. Sum DDT concentrations in the blubber ranged from 17 to 337 and 654 to 4430 microg/kg wet weight in females and males, respectively. Similarly, Sigma45CB concentrations ranged from 49 to 386 and 268 to 1634 microg/kg wet weight in females and males, respectively. The mean transmission of SigmaDDTs and ICES7CBs between a genetically determined mother-offspring pair was calculated at 46% and 42%, respectively. Concentrations of organochlorine pesticides determined in the present study are within similar range to those reported for Hector's dolphins (Cephalorhyncus hectori) from inshore New Zealand waters.

Grasping with a soft glove: intrinsic impedance control in pneumatic actuators.

The interaction of a robotic manipulator with unknown soft objects represents a significant challenge for traditional robotic platforms because of the difficulty in controlling the grasping force between a soft object and a stiff manipulator. Soft robotic actuators inspired by elephant trunks, octopus limbs and muscular hydrostats are suggestive of ways to overcome this fundamental difficulty. In particular, the large intrinsic compliance of soft manipulators such as 'pneu-nets'-pneumatically actuated elastomeric structures-makes them ideal for applications that require interactions with an uncertain mechanical and geometrical environment. Using a simple theoretical model, we show how the geometric and material nonlinearities inherent in the passive mechanical response of such devices can be used to grasp soft objects using force control, and stiff objects using position control, without any need for active sensing or feedback control. Our study is suggestive of a general principle for designing actuators with autonomous intrinsic impedance control.

Local superficial radiotherapy in the management of minimal stage IA cutaneous T-cell lymphoma (Mycosis Fungoides).

PURPOSE: To evaluate the impact of local superficial radiotherapy with respect to local control, survival, and toxicity for patients with "minimal" stage IA cutaneous T-cell lymphoma (Mycosis Fungoides). METHODS AND MATERIALS: Between 1954 and 1996 a total of 21 patients were identified as receiving curative local superficial radiation (LSR) for minimal stage IA Mycosis Fungoides. All patients had pathologic documentation at diagnosis and at the time of suspected recurrences and no patient received prior radiation. Ten patients were treated with 100-280 Kv (A1), and 11 with 4-12 Mev electrons. Nine patients had failed prior therapies (steroids: 4; PUVA: 3; BCNU: 1; UVB: 1) and six received adjuvant therapy after completion of LSR (PUVA: 5; steroids: 1). Minimum follow-up was 1 year. RESULTS: The median follow-up was 36 months (13-246), and the median age when commencing LSR was 55 years (27-73). All patients were Caucasian, and 11 were male. A total of 32 lesions were identified in 21 patients; 13 patients had unilesional disease, 5 patients had 2 lesions, and 3 had 3 lesions. A total of 33 fields were treated with a median treatment surface area of 107 cm2 (11-785). The median surface dose was 20 Gy (6-40), with 17 patients receiving a dose > or = 20 Gy. The median fraction number was 5 for all fields, but was 10 for the fields receiving 20-40 Gy. The complete response rate was 97%, and all patients were alive at last evaluation. All failures were cutaneous. One patient had persistent disease (treated with 6 Gy), and three failed locally at 52 months (8 Gy), 16 months (20 Gy), and 4 months (20 Gy). None of these patients received adjuvant therapy. Two patients failed in distant skin sites and were salvaged. The actuarial DFS for the entire group at 5 and 10 years was 75 and 64%, respectively, with local control of 75% at both time intervals. For the 13 patients with unilesional disease, the DFS was 85% at 10 years. For those treated with doses > or = 20 Gy, the DFS was 91% as was local control (no distant failures). Toxicity included mild erythema and dry desquamation acutely. Chronic toxicity included dermatitis [2], and telangiectasia [1]. No second cutaneous malignancies or hematologic toxicity was noted. CONCLUSION: Patients with minimal Stage IA Mycosis Fungoides may be managed effectively with local superficial radiation alone without adjuvant therapy. Distant failure is unusual and patients should receive a minimum surface dose of 20 Gy, which offers excellent local control. Sequalae of therapy are minimal.

Prognosis with newly diagnosed mycosis fungoides after total skin electron radiation of 30 or 35 GY.

PURPOSE: To determine the prognosis of new patients with T1-4N0-1B0M0 mycosis fungoides treated with total skin electron beam radiation. METHODS AND MATERIALS: 25 consecutive patients received 30 Gy with 3 or 4 MeV electrons in 1977-1980; 121 received 35 Gy with 4 MeV in 1980-1992. Response rates, relapse-free survival, and overall and cause-specific survivals were assessed by explicit criteria. The relationships of T, N, gender, age, and radiation technique to prognosis were investigated by regression statistics. RESULTS: The average age was 55 years and the male:female ratio was 1:4. Forty-four percent were T1N0 and 34% were T2N0. The overall complete response rate was 82%, and lower T status, more radiation, and female gender were independently and positively associated with response. Median follow-up was 5.2 years. T1 patients who entered remission had a higher relapse-free survival compared to T2 through T4 patients. Thirty-four percent of T1 patients remained relapse-free at 6 years, compared to fewer than 20% of T2-4 patients. For all 146 patients the median overall survival was not reached at 15 years. Only 8 of 29 deaths were related to mycosis fungoides and these were significantly associated with higher T. The 54 T1N0 patients who had 35 Gy had a 10-year mycosis fungoides-specific survival of 100%. CONCLUSION: Total skin electron beam radiation gives good results with T1N0B0M0 disease. T3-4 disease is less likely to respond, it relapses more quickly, and it implies a poorer survival, but radiation offers palliation. T2 responds like T1, but relapses like T3-4. T2 also implies an intermediate survival. These results have implications for staging, informed consent, optimizing radiation treatment, and clinical trials.

Total skin electron beam therapy followed by adjuvant psoralen/ultraviolet-A light in the management of patients with T1 and T2 cutaneous T-cell lymphoma (mycosis fungoides).

PURPOSE: Patients with mycosis fungoides [cutaneous T-cell lymphoma (CTCL)] may benefit from adjuvant therapy after completing total skin electron beam therapy (TSEBT). We report the results for T1/T2 CTCL patients treated with adjuvant oral psoralen plus ultraviolet light (PUVA) with respect to overall survival (OS), disease-free survival (DFS), salvage of recurrence, and toxicity. METHODS AND MATERIALS: Between 1974 and 1993, TSEBT was administered to a total of 213 patients with CTCL. Records were reviewed retrospectively, and a total of 114 patients were identified as having T1 or T2 disease. Radiotherapy was provided via a 6-MeV linac to a total of 36 Gy, 1 Gy/day, 4 days/week, for 9 weeks. Beginning in 1988, patients were offered adjuvant PUVA within 2 months of completing TSEBT. This was started at 0.5-2 J/m2, 1-2 treatments/week, with a taper over 3-6 months. Therapy then continued once per month. There were 39 T1 and 75 T2 patients. Six T1 (15%) and eight T2 (11%) patients were treated with adjuvant PUVA. A further 49% of the 114 patients received adjuvant systemic therapy, 3% received spot external beam, 4% received adjuvant ECP, 2% received topical nitrogen mustard, 22% received a combination of therapies exclusive of PUVA, and 9% received no adjuvant therapy. Patients were balanced in all subgroups based on pre-TSEBT therapy. The median age of the cohort was 58 (range 20-88), with a median follow-up time of 62 months (range 3-179). RESULTS: Within 1 month after completing of TSEBT, 97% of T1, and 87% of T2 patients had achieved a complete remission. Stratified by adjuvant therapy, none of six T1 and one of eight T2 patients who received adjuvant PUVA failed within the first 3 years after completion of TSEBT. A total of 43% of the T1 and T2 patients receiving other or no adjuvant treatment failed within the same time course. The 5-year OS for the entire cohort was 85%. Those who received PUVA had a 5-year OS of 100% versus a 5-year OS for the non-PUVA group of 82% (p < 0.10). The 5-year DFS for the entire cohort was 53%. Those who received PUVA had a 5-year DFS of 85% versus a 5-year DFS for the non-PUVA group of 50% (p < 0.02). By T stage, those with T1 receiving PUVA exhibited no relapses, whereas those with T1 not treated with PUVA had a crude relapse rate of 36%. Median DFS was not reached at 103 months for the T1 adjuvant PUVA patients versus 66 months for the non-PUVA patients (p < 0.01). For those with T2, crude relapse rates were 25% and 55%, respectively, with DFS of 60 (median DFS not reached) and 20 months (p < 0.03). The 5-year DFS for patients salvaged with PUVA was 50%. Toxicity of adjuvant and salvage PUVA therapy was acceptable, with only two patients requiring a reduction in PUVA dosage. CONCLUSION: PUVA can maintain remissions in patients with CTCL after TSEBT. There is a significant benefit in DFS but no statistically significant improvement in OS. Prospective, randomized data are needed to confirm these results. PUVA is also effective as a salvage therapy after TSEBT in early-stage patients with recurrence, with acceptable toxicity.

Fluorescent markers for hypoxic cells: a study of nitroaromatic compounds, with fluorescent heterocyclic side chains, that undergo bioreductive binding.

Several novel compounds having both a 2-nitroimidazole nucleus and a fluorescent ring system in their molecular structure were prepared and evaluated as potential fluorescent probes for hypoxia. Bioreduction of nitroimidazoles, which is inhibited by oxygen, is known to lead to binding of bioreductive metabolites to cellular macromolecules and this provides a mechanism for binding the fluorescent moiety to hypoxic cells. These compounds can incorporate a wide range of fluorophors and can therefore be designed to suit the laser-line wavelengths available for excitation of fluorescence in the flow cytometer. Several nitroimidazoles with naphthalimide side chains were rapidly taken up into cells and became concentrated in the cells, thus reducing their concentration in the extracellular medium. This suggests a potential microscopic bioavailability problem with probes of this type when used in vivo as they would become progressively depleted in the extracellular fluid as they diffused from blood vessels, through layers of packed cells in tumors, to the hypoxic cells where they could undergo hypoxia-specific metabolism. Synthesis of nitroimidazoles with coumarin fluorophors led to several potentially useful probes for hypoxia; substituents on the coumarin fluorophor had a marked effect on the cellular fluorescence of these compounds.

Synthesis and biochemical evaluation of analogues of aminoglutethimide based on phenylpyrrolidine-2,5-dione.

A series of (aminophenyl)pyrrolidine-2,5-diones has been prepared that bear structural similarities to aminoglutethimide (1, 3-(4-aminophenyl)-3-ethylpiperidine-2,6-dione). The inhibitory activity of these compounds was evaluated toward human placental aromatase and bovine adrenal cholesterol side chain cleavage (CSCC) enzyme assay systems. Selective, competitive inhibition of the aromatase enzyme system was demonstrated by 5 (3-(4-aminophenyl)-1-methyl-pyrrolidine-2,5-dione, Ki = 1.75 microM), 6 (3-(4-aminophenyl)-1,3-dimethylpyrrolidine-2,5-dione, Ki = 1.75 microM), 7 (3-(4-aminophenyl)-3-methylpyrrolidine-2,5-dione, Ki = 0.8 microM), and 8 (3-(4-aminophenyl)-3-ethylpyrrolidine-2,5-dione, Ki = 1.0 microM). Compound 15 (3-(4-aminophenyl)pyrrolidine-2,5-dione) proved unexpectedly difficult to prepare following standard methods and was only moderately inhibitory toward aromatase (IC50 = 20 microM). Compound 16 (3-(4-aminophenyl)-3-ethyl-1-methylpyrrolidine-2,5-dione) was weakly inhibitory toward testosterone aromatization and totally inactive toward androstenedione aromatization. These compounds were either weak or ineffective inhibitors of the CSCC enzyme systems, while 1 gave Ki values toward aromatase and CSCC enzymes of 0.68 and 14 microM, respectively. The unsubstituted phenylpyrrolidinediones were inactive in either system, and the 4-nitrophenyl derivatives exhibited weak, nonselective inhibition, indicating the importance of the primary amine moiety for potent inhibition of aromatase activity.

Adhesion of enteropathogenic Escherichia coli to pig intestinal brush borders: the existence of two pig phenotypes.

An in-vitro test that demonstrates adhesion of K88-positive Escherichia coli to brush borders prepared from the small intestine of the pig is described. K88-positive E. coli adhered to the brush borders from some pigs ("positive" pigs) but not others ("negative" pigs). The sires of the pigs tested could be placed into two groups, namely, those that sired only "positive" piglets, and those that sired a mixture of "positive" and "negative" piglets. The incidence of the two phenotypes in litters indicated that "positive" and "negative" piglets arose as a result of simple Mendelian inheritance. It is suggested that "negative" pigs could be bred and that they might have a natural resistance to neonatal infection with K88-positive E. coli.

Idiopathic renal arteriovenous fistula. Spontaneous closure.

A large and symptomatic idiopathic renal arteriovenous (AV) fistula closed over a two-year period of clinicoradiologic observation. This feature of idiopathic renal AV fistulas has not been reported previously, to our knowledge. If the presenting symptoms permit nonintervention, not only the trauma-related but also the idiopathic renal AV fistula can be conservatively managed and may heal spontaneously.

Gonadal stromal tumor in black male.

A twenty-five-year-old black male presented with a right testicular mass which had progressively increased in size over three years. He was in good health and noted no other general abnormalities. Taking all malignant precautions, excisional biopsy of the lesion revealed gonadal stromal tumor by frozen section. The testis was left in situ, and the patient has continued to remain asymptomatic.

Epidemiologic association between Gonorrhea and prostatic carcinoma.

The curves for death rates from prostatic cancer and gonorrhea incidence rates in Denmark, over a span of thirty years, matched well with a lag period of forty-five years. Moreover, a retrospective study conducted in the United States involving 75 cancer patients and 75 age-matched controls demonstrated a statistically significant association between gonorrheal infection and subsequent development of prostatic carcinoma. Two postulates are presented: the viral-venereal and the chronic infection theories. The recent increase in incidence of prostatic cancer in the United States could be the beginning of an epidemic in which astronomically high rates may be reached.

Mixed mesodermal tumor of urinary bladder: a light and electron microscopic study.

Light and ultrastructural findings in a mixed mesodermal tumor of the urinary bladder are reported. The mesenchymal component of the tumor contained undifferentiated mesenchymal cells and cells with chondroblastic differentiation. The neoplastic chondrocytes displayed an abundance of cytoplasmic microfilaments and had a scalloped cell surface.

Electron beam treatment for cutaneous T-cell lymphoma.

Total skin electron radiation has proven efficacy in treating MF. It is a complex technique that requires a dedicated radiation team, involving physicists, radiotherapists, and radiation oncologists. A center must treat a sufficiently high volume of patients to justify the development of TSE, with appropriate organization, time, and expense. The radiation team should be an integral part of a multidisciplinary clinical group, including medical oncologists, dermatologists, pathologists, and nurses. In these contexts, TSE has appropriately been developed in a limited number of centers. Cooperation between these centers is essential for further refinement of TSE techniques and for evolution of the role of TSE in the management of most patients with MF.

Patterns of care for carcinoma of the prostate gland: results of a national survey of 1984 and 1990.

BACKGROUND: The annual incidence of carcinoma of the prostate gland increased from an estimated 76,000 cases in 1984 to 200,000 in 1994. Part of this increase may be the result of increased detection. Management of the disease has also changed. To measure such changes, the American College of Surgeons conducted a patient care evaluation study of carcinoma of the prostate gland. STUDY DESIGN: Information was voluntarily submitted by cancer registrars on forms designed by a team of specialists. Data were received from 730 hospitals (of 2,000 hospitals invited for the study) on 14,716 patients with newly diagnosed adenocarcinomas of the prostate gland in 1984 and from 1,035 hospitals for 23,214 patients with carcinoma of the prostate gland in 1990. RESULTS: From 1984 to 1990, there was increased diagnostic use of the prostate specific antigen (PSA) test (from 5.1 to 66.4 percent of incident carcinomas) and transrectal ultrasound (TRUS) (0.9 to 19.7 percent). Use of the prostatic acid phosphatase assay declined from 62.4 to 47 percent. Although the proportion of early stage (0, I, II) disease increased for all racial or ethnic groups combined, the greatest increase was for whites (from 57.3 to 60.6 percent), while the increase for African-Americans was less (from 46.9 to 48.3 percent). The use of radical prostatectomy without radiation therapy or chemotherapy increased from 7.3 to 20.3 percent and the proportion of patients receiving no carcinoma-directed treatment decreased from 37.8 to 30 percent. Radiation therapy remained the same. Hormone therapy without radical prostatectomy declined from 24.4 to 19.7 percent. African-Americans had a lower five-year survival rate than whites, even when stratified for stage. CONCLUSIONS: The diagnostic use of the PSA test and TRUS increased markedly by 1990 and may have contributed to the increased diagnosis of carcinomas of the prostate gland and the earlier stage at diagnosis. The overall use of radical prostatectomy has increased and the proportion of patients receiving no treatment has decreased. African-Americans had a lower five-year survival rate than other groups, even when stage was controlled.

The development of eimerian infections during the first eight months of life in unweaned beef calves in a dry tropical region of Australia.

The development of coccidial infections in 21 free-ranging, unweaned beef calves from birth to 8 months was investigated by examining faecal samples for oocysts. Most calves commenced shedding oocysts within a month of birth, and had shed all nine species identified by 3-4 months. Oocysts were shed by three calves as young as 12 and 13 days. The oocysts species shed earliest, and the commonest thereafter, were Eimeria bovis, E. ellipsoidalis and E. zuernii. Although several oocyst counts between 5.0 X 10(3) and 114.0 X 10(3)g-1 of faeces of these potentially pathogenic species were recorded there was no clinical disease. Some calves shed oocysts approximately four times more frequently than others, and individual species counts greater than or equal to 5.0 X 10(3)g-1 were confined to 10 of the calves. Intermittent oocyst shedding continued throughout the study with a similar distribution of oocyst species from all calves.