Agreement between prenatal ultrasonography and fetal autopsy findings: a retrospective study of second trimester terminations of pregnancy.

OBJECTIVES: To estimate the agreement between prenatal ultrasonography observations at 16 - 21 gestational weeks and fetal autopsy findings in pregnancies terminated because of fetal anomalies. STUDY DESIGN: This 4½ year retrospective study includes consecutive fetuses that were terminated because of fetal malformation and/or chromosomal anomaly diagnosed in the second trimester. Only fetuses that had undergone fetal anatomy scanning by an obstetrician trained in fetal ultrasound before the termination and with available fetal autopsy reports were included. The cases were identified through the malformation registry database of our ultrasound unit. The sensitivity and specificity of ultrasound were calculated per organ system. When estimating the agreement between ultrasound results and autopsy findings, the cases were allocated to one of four categories according to the degree of concordance between ultrasound and autopsy findings: full agreement, near match, partial agreement and unconfirmed ultrasound findings. RESULTS: 71 of 95 pregnancy terminations due to fetal malformations met the inclusion criteria and constitute our study population. The sensitivity of ultrasonography with regard to malformations in the brain and spine was 100 % (27/27) and with regard to malformations in the internal organ system (including malformations in the urogenital and gastrointestinal systems and in the abdominal wall and diaphragm) was 91 % (30/33). The corresponding figures for malformations in the cardiovascular and skeletal organ systems were 63 % (17/27) and 71 % (25/35), respectively. The specificity was lowest for malformations in the central nervous system and internal organ system (33/38, 87 % and 39/44, 89 %, respectively). There was full agreement between the ultrasound and autopsy findings in 44 % (31/71) of all cases and a near match in 46 % (33/71) of cases. In almost 10 % (7/71) of the pregnancies, the ultrasound findings were only partially confirmed or not confirmed by autopsy. In one case the discrepancy between the ultrasound and autopsy findings suggests that the pregnant woman might have decided to terminate the pregnancy on the basis of incorrect interpretation of ultrasound findings. CONCLUSION: Even though the agreement between ultrasound and autopsy findings was acceptable from a clinical point of view, agreement with regard to the detailed description of malformations was far from perfect. The detection rates were suboptimal for the cardiovascular and skeletal organ systems.

Can cytotoxic dose-intensity be increased by using granulocyte colony-stimulating factor? A randomized controlled trial of lenograstim in small-cell lung cancer.

PURPOSE: The use of granulocyte colony-stimulating factor (G-CSF) to increase cytotoxic dose-intensity was assessed in a randomized trial in better-prognosis small-cell lung cancer (SCLC). Both control and G-CSF arms were subject to the same dose-intensification strategy. PATIENTS AND METHODS: Patients with newly diagnosed SCLC and either no or one adverse prognostic factor were randomized to receive vincristine, ifosfamide, carboplatin, and etoposide (VICE) alone or with recombinant human (rHu)G-CSF (lenograstim) 5 micrograms/kg/d between cycles. Six chemotherapy cycles were given, with prophylactic cranial irradiation after cycle 1 and thoracic irradiation after cycle 3. There was no fixed dose interval. In both arms, patients were eligible for re-treatment when the WBC count was > or = 3 x 10(9)/L and platelet count was > or = 100 x 10(9)/L. No dose reductions were permitted. Dose-intensity was expressed relative to standard every-4-weeks VICE. RESULTS: Sixty-five consecutive patients in one institution were randomized to control (n = 31) or G-CSF (n = 34). WBC and neutrophil counts were consistently higher in G-CSF patients than in the control group, but there were no significant differences in the incidence of febrile neutropenia, antibiotic or transfusion requirements, or days in hospital. In both treatment arms, the median dose-intensity was greater than one for each cycle (control group, P = .0009; G-CSF group, P = .0001). The G-CSF group received a significantly higher dose-intensity than the control group, with the greatest difference in the first three cycles (1.34 v 1.17, P = .001). There were more chemotherapy-related deaths in the G-CSF group than in the control group (six v one), but this group had a better 2-year survival rate (32% with G-CSF, 95% confidence interval [CI], 16 to 48; 15% with controls, 95% CI, 2 to 27). CONCLUSION: The dose-intensity of VICE chemotherapy was increased in both groups. Patients randomized to receive G-CSF achieved a significantly higher dose-intensity than controls. Despite early toxicity, they had a better 2-year survival rate.

Randomized phase II study of temozolomide given every 8 hours or daily with either interferon alfa-2b or thalidomide in metastatic malignant melanoma.

PURPOSE: Temozolomide is an imidazotetrazine with a mechanism of action similar to dacarbazine and equivalent activity in melanoma. It is well tolerated and is a candidate for combination chemotherapy and schedule manipulation. In this study, we combined temozolomide with interferon alfa-2b and, separately, with thalidomide, and we administered temozolomide alone in a compressed schedule. The objectives of this randomized phase II, two-center study were to determine response rates, overall survival, and tolerability of the regimens in patients with advanced metastatic melanoma. PATIENTS AND METHODS: One hundred eighty-one patients with metastatic melanoma were randomly assigned to receive up to six 4-weekly cycles consisting of temozolomide 200 mg/m2 every 8 hours for five doses, or temozolomide 200 mg/m2 daily for days 1 to 5 plus interferon alfa-2b 5 MU (million International Units) subcutaneously three times a week, or temozolomide 150 mg/m2 (increased after one cycle to 200 mg/m2) daily on days 1 to 5 plus thalidomide 100 mg daily days 1 to 28. RESULTS: The treatment arms were well balanced for known prognostic factors. Median survival was 5.3 months for 8-hourly temozolomide, 7.7 months for temozolomide/interferon, and 7.3 months for temozolomide/thalidomide; and 1-year survivals were 18%, 26%, and 24%, respectively. Response or disease stabilization occurred in 20% of patients (95% confidence interval [CI], 10% to 33%) given 8-hourly temozolomide, 21% (95% CI, 12% to 33%) given temozolomide/interferon, and 25% (95% CI, 15% to 38%) given temozolomide/thalidomide. Grade 3 or 4 nonhematologic toxicities were similar in each arm except for infection, which was more frequent with 8-hourly temozolomide. There were fewer instances of grade 3 or 4 myelotoxicity with temozolomide/thalidomide. CONCLUSION: Of the three regimens tested, the combination of temozolomide and thalidomide seems the most promising for future study.

Use of hematopoietic progenitors in whole blood to support dose-dense chemotherapy: a randomized phase II trial in small-cell lung cancer patients.

PURPOSE: Small-cell lung cancer (SCLC) is exquisitely chemosensitive, but few patients are cured by conventional chemoradiotherapy. Recent studies suggest that increased cytotoxic dose-intensity might improve survival. In this randomized phase II study, we tested the feasibility of dose intensification using sequential reinfusion of hematopoietic progenitors in whole blood. PATIENTS AND METHODS: SCLC patients with a favorable prognosis were treated with six cycles of ifosfamide, carboplatin, and etoposide (ICE), at 4-week (standard treatment) or 2-week (intensified treatment) intervals. Intensified treatment was supported by daily subcutaneous filgrastim injections and reinfusion of 750 mL of autologous blood collected immediately before each cycle. RESULTS: Fifty consecutive patients were randomized to standard (n = 25) or intensified (n = 25) ICE. A total of 94% completed at least three treatment cycles, and 70% completed six cycles; 96% of treatments were given at full dose. The planned dose-intensity was 1.0 for standard and 2.0 for intensified ICE. The median received dose-intensity for cycles 1 through 3 was 0.99 (range, 0.33 to 1.02) for the standard treatment arm and 1.80 (range, 0.99 to 1.97) for the intensified treatment arm (P <.001). Over all six cycles, the median received dose-intensity was 0.95 (range, 0.17 to 1.03) for the standard treatment arm and 1.60 (range, 0.60 to 2.01) for the intensified treatment arm (P <.001). Febrile neutropenia was more common on the standard treatment arm (84% v 56%), resulting in more days of intravenous antibiotics (median, 10 v 3 days; P =.035). Transfusion requirements were similar in the two groups. CONCLUSION: Sequential reinfusion of hematopoietic progenitors in whole blood can safely support substantial increases in dose-intensity of ICE chemotherapy for SCLC.

Clinical and quality of life outcomes in the first United Kingdom randomized trial of endobronchial brachytherapy (intraluminal radiotherapy) vs. external beam radiotherapy in the palliative treatment of inoperable non-small cell lung cancer.

BACKGROUND AND PURPOSE: A randomized controlled trial was designed to evaluate the clinical and quality of life (QL) outcomes of patients receiving endobronchial brachytherapy (EBT) or external beam radiotherapy (XRT) as a primary palliative treatment in advanced lung cancer. MATERIALS AND METHODS: Ninety-nine patients presenting de novo with lung cancer were randomized to receive EBT or XRT. Eleven key symptoms or clinical signs were assessed by clinicians and patient ratings using self-assessment questionnaires were obtained at the same time. The primary endpoints were a comparison of EBT and XRT for symptom relief and acute and late side-effects (palliation) and their effect on patients' functional status and patient-rated QL outcomes. A secondary objective was a comparison of clinician assessments with patient self-reported symptoms. RESULTS: Both treatments produced good levels of symptom relief. They were better for XRT at the expense of more acute morbidity. Late side-effects were similar. The functional status of patients was well maintained and changed similarly with time in both groups. XRT gave a better duration of palliation. Twenty-eight percent of XRT patients required EBT (at a median time of 304 days) whereas 51% of EBT patients subsequently had XRT (at a median of 125 days). There was a significant modest gain in median survival with initial XRT (287 vs. 250 days). When clinician and patient assessments were compared, doctors were found to underestimate the severity of breathlessness, anorexia, tiredness and nausea. CONCLUSIONS: Fractionated XRT is preferred to EBT as an initial treatment in better performance patients because it provides better overall and more sustained palliation with fewer retreatments and a modest gain in survival time. QL assessment is required in the evaluation of palliative treatments because clinicians frequently underestimate the incidence and severity of key symptoms.

A comparison of the inflammatory response to a polydimethylsiloxane implant in male and female Balb/c mice.

The implantation of biomaterials elicits a host response that influences the long-term behavior of implanted medical devices. This foreign body response is governed by cells of the immune system. Because sexual dimorphism in the immune system is well-established, a comparative study of the foreign body response in male and female mice was initiated. Eight-week-old male and female Balb/c mice received two subcutaneous implants in the interscapular region of a smooth peroxide-catalyzed polydimethylsiloxane (PDMS) and were sacrificed at 2, 14, 42, 70, and 105 days after implantation (n = 6 per sex per time point). Controls for each time point underwent the surgical procedure but received no implant. Tissue from the implant or surgical site was fixed, processed, and paraffin-embedded for histopathological evaluation and immunohistochemical (IHC) staining for tumor necrosis factor-alpha TNF-alpha) and interleukin-1 beta (IL-1beta). In control animals, an inflammatory response was observed at 2 days that was decreased by 14 days and absent after 42 days. At 2 and 14 days after PDMS implantation, a mild to moderate inflammatory reaction was observed around implants. The peak response was seen at 14 days, and granulation tissue, composed primarily of fibroblasts, macrophages, and neutrophils, was first observed at this time. After 105 days, the implantation site was surrounded by mature connective tissue, which had minimal numbers of macrophages and neutrophils, with severity scores that did not differ significantly in males and females. The immunostaining for TNF-alpha and IL-1beta followed similar temporal patterns, with both reaching a peak at the two week time point and remaining elevated, compared to level of expression in the controls, throughout the 105 day observation period. Staining for both cytokines in the implanted animals was generally higher in females than in males, although this difference was significant only for IL-1beta. These results suggest subtle differences between males and females in the activity of peri-implant inflammatory cells.

Differences in the response to oxidative stress and mutant frequency in CD (Sprague-Dawley) and Fisher 344 rats due to an induced inflammatory response.

In this study, the rodent air pouch model was used to examine the production and processing of oxidative DNA damage in two strains of rats commonly used in toxicity testing. An inflammatory response was induced by injecting zymosan A (50 mg) into an air pouch on male CD (Sprague-Dawley [S-D]) and Fisher 344 (F-344) rats, and the animals were then sacrificed at 1, 3, 7, 14, and 28 days (n = 6 per time point per strain). Tissues from the lining of the air pouch were collected for 8-hydroxy-2'-deoxyguanosine (8-OH-dG) analysis and for paraffin embedding. Significant (P < 0.01) increases in 8-OH-dG were observed after 1 day in the DNA from cells lining the air pouch of zymosan A-treated versus control S-D (101.5 +/- 27.1 vs. 23.1 +/- 2. 7 8-OH-dG/dG x 10(5)) and F-344 (51.4 +/- 5.3 vs. 14.4 +/- 0.6 8-OH-dG/dG x 10(5)) rats. By 28 days, 8-OH-dG levels had returned to background in S-D rats, but remained elevated in F-344 rats. The frequency of apoptosis was evaluated using the in situ end-labeling (TUNEL) assay, which revealed that zymosan A-treated S-D rats had a significantly (P < 0.05) higher frequency of apoptosis compared to zymosan A-treated F-344 rats. To examine the potential consequences of these differences in endogenously produced DNA damage and apoptosis, we measured mutations at the hprt locus in fibroblasts of the pouch lining and observed a significant (P < 0.05) increase in the mutant frequency at day 28 in F-344 rats (54.2 +/- 13.6 mutants per 10(6) cells) compared to controls (4.5 +/- 2.0 mutants per 10(6) cells). The mutant frequency was not increased in S-D rats. These data demonstrate that strain differences in the production and processing of oxidative DNA damage due to an inflammatory response may impact the long-term pathologic consequences of chronic inflammation. Environ. Mol. Mutagen. 35:336-342, 2000 Published 2000 Wiley-Liss, Inc.

Stimulated pulmonary cell hyperplasia underlies resistance to alpha-naphthylthiourea.

The rodenticide alpha-naphthylthiourea (ANTU) causes pulmonary edema and pleural effusion that leads to death via pulmonary insufficiency. Rats become resistant to the lethal effect of ANTU if they are first exposed to a small, nonlethal dose of ANTU. Young rats are also resistant to ANTU. The mechanism by which rats develop resistance by a prior, small dose exposure has yet to be determined. Growth factor induced-pulmonary hyperplasia has been demonstrated to attenuate ANTU-induced lung leak. We hypothesized that a small dose of ANTU protects against a large dose through pulmonary cell hyperplasia induced by the protective dose. Furthermore, we hypothesized that this hyperplasia is associated with altered transcription of growth factors. Male Sprague-Dawley rats (175-225 g) were treated with a low dose of ANTU (5 mg ANTU/kg; ANTU(L)) 24 h before challenge with a 100% lethal dose of ANTU (70 mg ANTU/kg; ANTU(H)) resulting in 100% protection against the lethal effect of ANTU(H). ANTU(L) protection against ANTU(H) lasted for 5 days, slowly phased out, all being lost by day 20. Injury was assessed by estimating pulmonary vascular permeability and through histopathological examination. ANTU(H) alone resulted in an increase in pulmonary edema leading to animal death. However, injury was prevented if the rats were first treated with ANTU(L). There was a stimulation of pulmonary cell hyperplasia in the lungs of ANTU(L) treated rats as measured by [3H]-thymidine and bromodeoxyuridine incorporation. Treatment with the antimitotic agent colchicine abolished ANTU(L)-induced resistance to ANTU(H). ANTU resistant rats were also resistant to the lethal effect of paraquat. Paraquat is not taken up by pneumocytes if they are undergoing hyperplasia. ANTU(L) administration resulted in an up regulation of gene transcription for keratinocyte growth factor, transforming growth factor-beta, keratinocyte growth factor receptor and epidermal growth factor receptor as determined through reverse transcription-polymerase chain reaction. A significant increase in transforming growth factor-alpha was not observed. These findings collectively suggest that ANTU(L)-induced pulmonary cell hyperplasia underlies resistance to ANTU(H). Furthermore, the stimulation of hyperplasia may be due to altered growth factor and growth factor receptor expressions.

Effects of dietary genistein exposure during development on male and female CD (Sprague-Dawley) rats.

Genistein is a naturally occurring isoflavone that interacts with estrogen receptors and multiple other molecular targets. Human exposure to genistein is predominantly through consumption of soy products, including soy-based infant formula and dietary supplements. A dose range-finding study was conducted as a prelude to a multigeneration bioassay to assess potential toxicities associated with genistein consumption. Genistein was administered in a soy- and alfalfa-free diet at 0, 5, 25, 100, 250, 625, or 1250 ppm to pregnant dams starting on Gestation day 7 and continuing throughout pregnancy. Dietary exposure of the dams continued through lactation, and pups were maintained on the same dosed feed as their mother after weaning until sacrifice at Postnatal day 50. Body weight and feed consumption of the treated dams prior to parturition showed a decreasing trend with a significant reduction at the highest dose. Litter birth weight was depressed in the 1250 ppm dose group, and pups of both sexes in that dose group had significantly decreased body weights relative to controls at the time of sacrifice. The most pronounced organ weight effects in the pups were decreased ventral prostate weight in males at the 1250 ppm dose and a trend toward higher pituitary gland to body weight ratios in both sexes. Histopathologic examination of female pups revealed ductal/alveolar hyperplasia of the mammary glands at 250 to 1250 ppm. Ductal/alveolar hyperplasia and hypertrophy also occurred in males, with significant effects seen at 25 ppm and above. Abnormal cellular maturation in the vagina was observed at 625 and 1250 ppm, and abnormal ovarian antral follicles were observed at 1250 ppm. In males, aberrant or delayed spermatogenesis in the seminiferous tubules relative to controls was observed at 1250 ppm. There was a deficit of sperm in the epididymis at 625 and 1250 ppm relative to controls, although testicular spermatid head counts and epididymal spermatozoa counts did not show significant differences from controls at these doses. Both sexes showed an increase in the incidence and/or severity of renal tubal mineralization at doses of 250 ppm and above. Dietary genistein thus produced effects in multiple estrogen-sensitive tissues in males and females that are generally consistent with its estrogenic activity. These effects occurred within exposure ranges achievable in humans.

Neurotoxicologic examination of rats exposed to 1,1,1-trichloroethane vapor for 13 weeks.

Large evoked potential and EEG changes occurred in a pilot study in Fisher 344 rats during exposure to 2000 ppm of 1,1,1-trichloroethane (1,1,1-T; a cleaning solvent with anesthetic properties). In the main study, rats were evaluated for persistent nervous system effects the week following exposure to 0, 200, 630, or 2000 ppm 1,1,1-T for 6 h/day, 5 days/week, for 13 weeks. Rats were clinically examined regularly and were given a functional observational battery monthly (FOB, including forelimb and hindlimb grip performance testing). After 13 weeks of exposure, the rats were evaluated by FOB and by visual, auditory, somatosensory, and caudal nerve-evoked potentials. After functional testing, a subgroup of rats had histopathologic examination of brain, spinal cord, peripheral nerves, and limb muscles. There were no post-exposure treatment-related findings in any parameter (FOB observations plus 39 dependent variables) except for a slightly smaller forelimb grip performance in the 2000-ppm exposure group. There was no recognized toxicologic significance for the difference in forelimb grip performance; a lack of findings in any other clinical, evoked potential or morphologic parameter did not support a diagnosis of neurotoxicity.

Chronic inhalation toxicity and oncogenicity of methyl methacrylate in rats and hamsters.

Male and female Fischer 344 rats were exposed to methyl methacrylate (MMA) monomer vapours at 0, 25, 100 and 400 ppm, 6 hr/day, 5 days/wk for 24 months and male and female Golden hamsters were exposed to similar vapour concentrations of MMA for 18 months. Parameters monitored throughout the study included clinical signs, individual body weights, haematology, clinical chemistry (rats only) and urinalyses (rats only). 10 rats per sex per exposure group were killed after 13 and 52 wk of exposure and all surviving rats were killed during wk 104-106. All surviving hamsters were killed at wk 78. Mortality and haematological, clinical chemistry and urinalyses parameters were not affected by MMA exposure. Body weights of male rats were not affected by exposure to MMA while body weights of female rats exposed to 400 ppm were lower than control values after wk 52. Male and female hamsters exposed to 400 ppm had body weight decreases ranging from 9 to 12% after wk 48. The nasal cavity was identified as the target organ for chronic toxicity in male and female rats exposed to 100 or 400 ppm. The microscopic nasal cavity changes occurred primarily in olfactory epithelium lining the dorsal meatus and consisted of degeneration of neuroepithelium, basal cell hyperplasia and atrophy of Bowman's glands. Hamsters did not have demonstrable nasal cavity microscopic changes. Chronic exposure to MMA vapour did not cause tumours in either rats or hamsters.

Naturally occurring porcine proliferative enteritis: pathologic and bacteriologic findings.

The lesions of porcine proliferative enteritis were studied by light and electron microscopic techniques in feeder pigs, fattening hogs, bred gilts, sows, and boars. The characteristic microscopic feature common to all age groups was proliferation of immature crypt epithelial cells, primarily in the ileum and the distal part of the jejunum. Similar changes were also observed in the midjejunum, cecum, and colon of a new swine. The earliest detectable microscopic lesion was focal proliferation of crypt epithelial cells with accompanying inflammation of the lamina propria and leukocytic exudate within affected crypt lumina. Lesions progressed to diffuse crypt cell proliferation, elongation of crypts, and loss of villi. Immature epithelial cells contained variable numbers of intracytoplasmic, nonmembrane-bound, curved organisms resembling Campylobacter sp bacteria. Similar organisms were within phagolysosomes of macrophages in the lamina propria and within the cytoplasm of crypt epithelial cells undergoing mitosis. Campylobacter sputorum subsp mucosalis was isolated from the ileal mucosa in 30 of 58 swine.

Experimentally induced porcine proliferative enteritis in specific-pathogen-free pigs.

Thirty-three, 10-week-old, specific-pathogen-free pigs were randomly allotted to 3 treatment groups: group 1--intragastrically given homogenized intestinal mucosa (crude inoculum) from pigs with naturally occurring proliferative enteritis; group 2--given cultures of Campylobacter sputorum subsp mucosalis; and group 3--controls. One pig from each group was killed 4, 7, 10, 14, 18, 21, 24, 28, 31, 36, and 38 days after inoculation. The earliest intestinal lesion observed in groups 1 and 2 was leukocytic exudate within crypt lumina and focal inflammation of the surrounding lamina propria. The lesions occurred primarily over ileal aggregated lymphoid nodules (Peyer's patches). These changes were followed by focal proliferation of immature crypt epithelial cells and infiltration of increasing numbers of macrophages into the lamina propria. Campylobacter sp-like organisms were observed within the cytoplasm of affected epithelial cells by light and electron microscopies. Lesions progressed to diffuse crypt cell proliferation, elongation of crypts, and loss of villi. Mucosal necrosis was not a prominent feature.

Porcine proliferative enteritis: experimentally induced disease in cesarean-derived colostrum-deprived pigs.

The hypotheses that porcine proliferative enteritis is an infectious disease and that Campylobacter sputorum subsp mucosalis (CSM) is involved in the development of this disease were experimentally tested. Three experiments were conducted with 10-week-old, cesarean-derived colostrum-deprived pigs. Of 22 pigs given homogenized mucosal scrapings (crude inocula) intragastrically, 15 had gross and/or microscopic lesions of proliferative enteritis. Of 10 pigs inoculated with cultures of both CSM and Salmonella cholerae-suis, 2 had evidence of proliferative enteritis. The 4 pigs treated with S cholerae suis only had diffuse fibrinous gastroenteritis without evidence of mucosal proliferation. Proliferative enteritis was produced in 1 of 5 pigs inoculated with pure cultures of CSM. Proliferative lesions in the intestine were characterized by the proliferation of immature crypt epithelial cells. Affected cells contained variable numbers of curved, intracytoplasmic Campylobacter sp organisms. The CSM organism was isolated from the intestinal mucosa of 8 pigs treated with either crude inocula or cultures of CSM.

Toxicologic and immunologic effects of sublethal doses of cyclopiazonic acid in rats.

Effects of cyclopiazonic acid (CPA) on humoral immunity, cell-mediated immunity, weight gain, organ weights, clinical chemical and hematologic values, and gross and microscopic lesions were evaluated. Four groups of rats, each containing 3 males and 3 females, were given 0, 0.1, 1, and 5 mg of CPA/kg of body weight intraperitoneally for 28 days. A dosage level of 5 mg/kg produced a significant (P less than 0.05) decrease in weight gain. Rats given 0.1 or 1 mg of CPA/kg had a significant (P less than 0.05) reduction in antibody titer against sheep RBC 5 days after injection. The 0.1 mg/kg group also had a significant reduction in antibody titer 7 days after injection. Microscopic lesions were limited to liver, and kidneys and were characterized by vacuolated to granular hepatocyte cytoplasm and dilated renal convoluted tubules, many having pyknotic nuclei and scattered hyaline casts.

Effect of pyrantel tartrate and carbadox on acquisition of the swine kidneyworm (Stephanurus dentatus) and other parasites by pigs on contaminated lots.

A combination of pyrantel tartrate (106 mg/kg of body weight) and carbadox (55 mg/kg of body weight) in ground feed was fed to 20 weaned pigs (av wt, 14.4 kg) for 42 days. Another group of 20 pigs included nontreated controls. The pigs were farrowed and suckled in a slat-floored farrowing house and had minimal exposure to the small intestinal threadworm (Stronglyoides ransomi) until they were placed on severely contaminated dirt lots at the start of the experiment. Five pigs from each of the two groups were necropsied on day 42. Carbadox was withheld from the feed for the 15 remaining treated pigs. All other pigs were necropsied when they attained market weight, 72 to 83 days layer. Treated pigs killed at market weight had 44% fewer (P less than 0.10) kidneyworms (Stephanurus dentatus) than did control pigs. A 17% increase (P less than 0.01) in the weights of livers of control pigs when compared with treated market-weight pigs was associated with an increase of fibrotic hepatic tissue of control pigs. Worm infections were reduced in the treated market-weight pigs: by 96% (P less than 0.05) for the large roundworm (Ascaris suum), 77% (P less than 0.01) for nodular worms (Oesophagostomum spp), and 64% (P less than 0.01) for the intestinal threadworm. There was some evidence for prophylaxis in market-weight pigs (P less than 0.10) against lungworms (Metastrongylus spp), but none against the whipworm (Trichuris suis) or thick stomach worms (Ascarops strongylina and Physocephalus sexalatus). Pigs given the pyrantel tartrate in feed until attaining market weight maintained a feed-to-gain ratio superior (7.1%) to that of nontreated pigs.

Thymic abnormalities and growth hormone deficiency in dogs.

A high frequency of occurrence of a wasting disease, unthriftiness, and retarded growth was observed in a group of inbred Weimaraner dogs. Affected pups had a small thymus gland, with a marked absence of thymic cortex. A litter of eight pups from a sire and dam that were known to have produced affected offspring was chosen for further study. The pups had normal concentrations of WBC and gamma-globulins and were able to produce antibody in response to Brucella abortus. Two pups in the litter developed a wasting syndrome and responded well to therapy with thymosin fraction 5. One pup that survived the wasting syndrome had a significant (P < 0.05) depression of its lymphocyte blastogenic response to phytohemagglutinin compared with its surviving littermates. Pups from this litter also lacked a normal increase in plasma growth hormone concentration after the injection of clonidine HCl. These pups had concurrent abnormalities of the thymus-dependent immune function and in growth hormone metabolism. The syndrome in these pups has some features in common with the syndrome in the Ames or Snell-Bagg strains of immunodeficient dwarf mice.

Coccidosis caused by Eimeria scabra in a finishing hog.

Coccidiosis caused by Eimeria scabra was diagnosed in a 60-kg finishing hog with severe diarrhea and weight loss. Fresh and fixed tissues from a farrowing to finishing operation in eastern Georgia were submitted. Examination of hematoxylin-eosin-stained sections of small intestine revealed large numbers of thick-walled oocysts and large macrogamonts. Although coccidiosis has been associated with diarrhea in baby pigs, coccidiosis as a cause of diarrhea in finishing swine is seldom reported.

Evaluation of immune response to artificial infections of Haemonchus contortus in Gulf Coast Native compared with Suffolk lambs.

The Gulf Coast Native (Native) breed of sheep among many others is identified as being relatively resistant to Haemonchus contortus, an abomasal nematode parasite of small ruminants. Understanding the mode of immune response that helps these breeds of sheep control infection could help design and implement appropriate control programs. In this experiment, the components of the immune response during the early infection period in resistant Native lambs were evaluated and compared with susceptible Suffolk breed of sheep. Groups (n=5) of six month old Native and Suffolk lambs were given infective larvae as one time (single) or trickle experimental infections. Fecal, blood, and serum samples were collected on days 0, 2, 7, 14 and 21 post-infection. Abomasal mucosa and regional lymph node samples were collected at the time of necropsy on days 14 and 21. There was no significant difference in number of worms recovered at necropsy but the ratio of adult versus larvae was significantly greater in single infected Suffolk than Native lambs. Native lambs had significantly greater numbers of mast cells and eosinophils in the abomasal mucosa and serum IgG production was significantly greater compared to Suffolk lambs. Native lambs also showed a trend of increased level of serum IgA and IgE compared to Suffolk lambs.