Dairy producer perceptions of the Farmers Assuring Responsible Management (FARM) Animal Care Program.

Dairy farms producing 98% of the US milk supply participate in the Farmers Assuring Responsible Management (FARM) Animal Care Program. Producers who sell milk to cooperatives or processors participating in FARM must follow program standards. The objectives of this study were to assess producer perceptions about the knowledge, experience, and value of FARM and to determine whether perceptions differ based on demographics. A concurrent triangulation design was implemented through collecting quantitative and qualitative data using a 30-question survey instrument. Quantitative questions aimed to address project objectives, and qualitative data were provided through 1 open-ended survey question that asked participants what they thought the main goal of the FARM program was. Participants offered additional feedback through providing text in comment boxes, writing on the back of the survey, or writing a separate letter and returning it with their survey. Quantitative data were analyzed using principal components analysis and modeling, and qualitative data were analyzed through thematic analysis. Dairy producers from cooperatives or processors that participate in the FARM program were recruited via electronic and postal mail. A total of 487 respondents from 40 states completed the survey. Of the survey participants, 414 (85.0%) answered the open-ended question and 190 (39.0%) provided additional qualitative feedback. Thematic analysis revealed 5 main themes: distrust of program, producers on the defense, anger, efficiency, and nostalgia. Of respondents, 73.6% reported being knowledgeable about the FARM Animal Care Program. Greater level of formal education and larger herd size were associated with greater producer knowledge. More dairy producer input in the revisions of FARM was identified as a need by 83.3% of respondents. Although 89.3% of respondents reported positive experiences with evaluations and relationships with evaluators, 45.6% did not think that the program had value overall. Respondent age was positively associated with perceived value of FARM. Respondent age was also significant in determining the reasons why FARM was considered to be important. Results indicate that to increase buy-in and positive perceptions from producers, future versions of FARM should solicit producer input during the development of program standards, target specific producer demographics for program promotion, and address perceived communication deficits and program inequalities. Findings from this study can be used to inform future versions of the program.

Sentinel lymph node biopsy for breast cancer: a suitable alternative to routine axillary dissection in multi-institutional practice when optimal technique is used.

PURPOSE: Previous studies have demonstrated the feasibility of sentinel lymph node (SLN) biopsy for nodal staging of patients with breast cancer. However, unacceptably high false-negative rates have been reported in several studies, raising doubt about the applicability of this technique in widespread surgical practice. Controversy persists regarding the optimal technique for correctly identifying the SLN. Some investigators advocate SLN biopsy using injection of a vital blue dye, others recommend radioactive colloid, and still others recommend the use of both agents together. PATIENTS AND METHODS: A total of 806 patients were enrolled by 99 surgeons. SLN biopsy was performed by single-agent (blue dye alone or radioactive colloid alone) or dual-agent injection at the discretion of the operating surgeon. All patients underwent attempted SLN biopsy followed by completion level I/II axillary lymph node dissection to determine the false-negative rate. RESULTS: There was no significant difference (86% v 90%) in the SLN identification rate among patients who underwent single- versus dual-agent injection. The false-negative rates were 11.8% and 5.8% for single- versus dual-agent injection, respectively (P <.05). Dual-agent injection resulted in a greater mean number of SLNs identified per patient (2. 1 v 1.5; P <.0001). The SLN identification rate was significantly less for patients older than 50 years as compared with that of younger patients (87.6% v 92.6%; P =.03). Upper-outer quadrant tumor location was associated with an increased likelihood of a false-negative result compared with all other locations (11.2% v 3. 9%; P <.05). CONCLUSION: In multi-institutional practice, SLN biopsy using dual-agent injection provides optimal sensitivity for detection of nodal metastases. The acceptable SLN identification and false-negative rates associated with the dual-agent injection technique indicate that this procedure is a suitable alternative to routine axillary dissection across a wide spectrum of surgical practice and hospital environments.

Altered expression of the DNA repair protein, N-methylpurine-DNA glycosylase (MPG) in breast cancer.

We examined expression of N-methylpurine-DNA glycosylase (MPG), a DNA repair enzyme that removes N-alkylpurine damage, in normal, malignant, and immortalized breast epithelial cells, and breast cancer cell lines (MDA-MB-231, MCF7, T47D). Northern analysis showed increased expression in cancer versus normal breast epithelial cells (2-24-fold). Southern blots revealed no gene amplification or polymorphisms. Immunofluorescence, immunohistochemistry, and Western blot analysis demonstrated increased MPG protein expression in the tumor cells that correlated with elevated glycosylase activity. Since MPG overexpression has been shown to be paradoxically associated with increased susceptibility to DNA damage, up-regulation of this gene may suggest a functional role in breast carcinogenesis.

Transfusion requirements of adolescents with severe haemophilia A.

The transfusion requirements of 75 adolescents with severe haemophilia A were studied during the five-year period 1973-77. The annual incidence of the 4935 episodes studied increased by a factor of 2.2 while the number of transfusions rose by a factor of 2.5 and the amount of therapeutic material used during the five years of the survey increased by a factor of 2.6. A further 166 bleeds occurred during periods of prophylaxis in 1976 and 1977, which generated a 25% increase in factor VIII used during those years. The increased usage of factor VIII in the years 1976 and 1977 was thus due mainly to increased numbers of transfusions given per bleed and to the use of prophylaxis but also to a slight increase in the units of factor VIII given in each dose. Twice weekly prophylaxis reduced the bleeding frequency by 30% and resulted in an increase of about 12% in usage of factor VIII. Prophylaxis given three times weekly reduced the bleeding frequency by about 60% at the cost of an increase of 77% in therapeutic materials. Iliopsoas, retroperitoneal, and abdominal wall bleeds were the commonest bleeds needing retransfusion within 24 hours, while bleeds into the extremities of the upper and lower limbs needed least retransfusions within 24 hours. Retroperitoneal bleeds needed the most transfusions per episode followed by iliopsoas, buttock, abdominal wall, and hip joint bleeds. The transfusion requirements of bleeds below the diaphragm tended to diminish steadily the more peripheral they became. This relationship did not hold for upper limb bleeds.

Twice weekly prophylactic therapy in haemophilia A.

Factor VIII-containing materials were administered to four severely affected haemophiliacs twice weekly in doses calculated to raise the factor VIII level to either 15% or 30% of average normal. The pooled results from those patients with statistically similar baseline bleeding frequencies showed a significant reduction in bleeding frequency on both doses in the first 48 hours. The 30% dose produced a more significant reduction than the 15% dose in the first 24 hours, but there was no significant difference between the two doses in the second 24 hours. It appears that to reduce the bleeding frequency of severely affected haemophiliacs by 60% would require a two-and-a-half-fold increase in therapeutic materials. A 90% reduction would need nine times the amount of material currently in use.

Practical guidelines for optimal gamma probe detection of sentinel lymph nodes in breast cancer: results of a multi-institutional study. For the University of Louisville Breast Cancer Study Group.

INTRODUCTION: Multiple radioactive lymph nodes are often removed during the course of sentinel lymph node (SLN) biopsy for breast cancer when both blue dye and radioactive colloid injection are used. Some of the less radioactive lymph nodes are second echelon nodes, not true SLNs. The purpose of this analysis was to determine whether harvesting these less radioactive nodes, in addition to the "hottest" SLNs, reduces the false-negative rate. METHODS: Patients were enrolled in this multicenter (121 surgeons) prospective, institutional review board-approved study after informed consent was obtained. Patients with clinical stage T1-2, N0, M0 invasive breast cancer were eligible. This analysis includes all patients who underwent axillary SLN biopsy with the use of an injection of both isosulfan blue dye and radioactive colloid. The protocol specified that all blue nodes and all nodes with 10% or more of the ex vivo count of the hottest node should be removed and designated SLNs. All patients underwent completion level I/II axillary dissection. RESULTS: SLNs were identified in 672 of 758 patients (89%). Of the patients with SLNs identified, 403 patients (60%) had more than 1 SLN removed (mean, 1.96 SLN/patient) and 207 patients (31%) had nodal metastases. The use of filtered or unfiltered technetium sulfur colloid had no impact on the number of SLNs identified. Overall, 33% of histologically positive SLNs had no evidence of blue dye staining. Of those patients with multiple SLNs removed, histologically positive SLNs were found in 130 patients. In 15 of these 130 patients (11.5%), the hottest SLN was negative when a less radioactive node was positive for tumor. If only the hottest node had been removed, the false-negative rate would have been 13.0% versus 5.8% when all nodes with 10% or more of the ex vivo count of the hottest node were removed (P =.01). CONCLUSIONS: These data support the policy that all blue nodes and all nodes with 10% or more of the ex vivo count of the hottest SLN should be harvested for optimal nodal staging.

Isolated pelvic perfusion for unresectable cancer using a balloon occlusion technique.

Previously irradiated recurrent pelvic malignancy is refractory to most treatment modalities. Ten patients with local recurrences (six with rectal cancer; three, anal cancer; and one, anorectal melanoma) were treated with a total of 17 courses of isolated pelvic perfusion chemotherapy (12 with multiple agents) using standard hemodialysis technology. Aortic and inferior vena caval occlusion was maintained via transfemoral balloon catheters, with a single intraoperative balloon disruption. Mean pelvic-systemic drug exposure ratios were 9.8:1 for fluorouracil, 4.8:1 for cisplatin, and 4.4:1 for mitomycin C. Results were three partial responses (two patients subsequently underwent resection) and three minor responses, all in patients with a visible tumor. Pelvic pain was relieved in six of eight symptomatic patients (mean duration, 4 months). Using limited access, this procedure produces high pelvic-systemic concentration gradients, prolonged palliation for recurrent pelvic cancers, and increased resectability in selected patients.

Surgical implications of primary gastrointestinal lymphoma of childhood.

Our purpose was to summarize information from a large single institution's experience regarding the role of surgical resection in the management of non-Hodgkin's lymphoma in children and adolescents. Fifty-eight children were treated for primary gastrointestinal non-Hodgkin's lymphoma. The tumors usually presented in the ileocolic region (n = 54). Twenty-one children presented with intussusception. Complete surgical resection of tumor was accomplished in 32 patients, partial resection in 20, and biopsy only in 6. All patients were given lymphoma protocols employing chemotherapy and irradiation. Forty-four (76%) of 58 patients are surviving from 1 year to greater than 20 years from diagnosis. Thirty-one of 32 patients who underwent complete resection followed by protocol management are surviving, compared with 13 of 26 children with residual gross disease. The results indicate that children with primary gastrointestinal non-Hodgkin's lymphoma benefit from complete surgical resection when feasible.

Decreased sensitivity to chloroquine and quinine of some Plasmodium falciparum strains from Senegal in September 1984.

The in vitro sensitivity of 135 Plasmodium falciparum isolates collected in the areas of Thies and Kaolack, Senegal, were studied in September 1984, by means of the 48 hr microtest with 3H-hypoxanthine incorporation. Results are available in 110 of 135 cases studied (81%). The isolates collected around Kaolack were found on average less sensitive to chloroquine than those from Thies (mean EC50 28 and 17 nmol/l of medium, respectively, P less than 0.05) and in 1 isolate a high degree of resistance was found (EC50 178 nmol/l). Some of those isolates also were studied using the WHO standard microtest and similar results were recorded. With both assays probit regression lines show EC99 in Kaolack greater than 114 nmol/l. These data suggest that in 1984 chloroquine resistance was possibly emerging in the extreme west of Africa. Sensitivity to quinine could be evaluated in 15 of 24 isolates tested. One of them, originating from Thies, was highly resistant to this drug (EC50 760 nmol/l) and 2 additional isolates with EC50s of 370 and 274 nmol have decreased sensitivity. These results suggest that quinine, as well as chloroquine, sensitivity should be monitored in the African region.

Free radical DNA adduct 8-OH-deoxyguanosine affects activity of Hpa II and Msp I restriction endonucleases.

8-OH-deoxyguanosine can diminish the ability of the restriction endonucleases Hpa II and Msp I to cleave DNA. The exact position of the adduct within the recognition site appears to determine the extent of the effect.

Augmentation of the lymphokine-activated killer cell response in head and neck cancer patients by combination interleukin-2 and interferon-alpha.

The majority of patients with head and neck cancer present with advanced disease (stage III and IV), for which current chemotherapeutic regimens offer dismal results. Although known to have defects in their cell-mediated immunity, their poor performance status makes them unlikely candidates for aggressive immunotherapeutic protocols because of associated severe toxicities. This study evaluates the effect of subthreshold recombinant interferon-alpha (rIFN-alpha) and interleukin-2 (rIL-2) on the generation of lymphokine-activated killer (LAK) cells from the peripheral blood of patients with head and neck cancers. In vitro treatment of patients' lymphocytes consisted of incubation in 1,000 U/mL rIL-2, 100 U/mL rIL-2, 100 U/mL rIFN-alpha, and 100 U/mL rIFN-alpha plus 100 U/mL rIL-2 for 4 to 5 days. Cytotoxicity was measured using a standard 4-hour chromium-51 (51Cr)-release assay with Raji (B lymphoblastoid) tumor target cells. LAK activity was arbitrarily defined as greater than 20% cytolysis of Raji target cells. LAK activity was generated in a smaller percentage of the head and neck cancer patients by 1,000 U/mL rIL-2 compared with normal adult donors: 54% versus 100%, p less than 0.05; IFN-alpha (100 U/mL) induced LAK activity in approximately 50% of the cancer patients. The addition of rIFN-alpha (100 U/mL) to rIL-2 (100 U/mL) resulted in LAK generation in a higher percentage of patients (83% versus 54%), as well as increased levels of cytotoxicity, p = 0.05. This combination also resulted in cytotoxicity levels equivalent to high-dose (1,000 rIL-2 U/mL). These in vitro data support a clinical trial to assess the therapeutic efficacy of combined low-dose rIL-2 and rIFN-alpha in vivo in head and neck cancer patients.

Is surgical excision necessary for atypical ductal hyperplasia of the breast diagnosed by Mammotome?

BACKGROUND: Core biopsy findings of atypical ductal hyperplasia (ADH) underestimates the diagnosis of malignancy by 18% to 88%. Using the Mammotome biopsy technique, more accurate assessment of the lesion is possible, making selective excision of these lesions a consideration. METHODS: The records of 62 patients who were found to have ADH at Mammotome biopsy and subsequently underwent excision of the lesion were reviewed. Patient data were statistically analyzed for predictors of malignancy at the time of surgical excision. RESULTS: Of the 62 patients, 9 (15%) had malignancy at excision. Variables predicting for malignancy included markedly atypical hyperplasia and incomplete removal of calcifications at Mammotome biopsy, a previous contralateral breast cancer, and a family history of breast cancer, with a combined sensitivity of 100% and specificity of 80%. CONCLUSIONS: Mild ADH found on Mammotome, not associated with a personal or family history of breast cancer, may not need excision if all calcifications have been removed.

Reliable lymphatic drainage to axillary sentinel lymph nodes regardless of tumor location within the breast.

BACKGROUND: This analysis was performed in order to determine whether primary tumor location in breast cancer affects the axillary sentinel lymph node (SLN) identification (ID) rate, the false negative (FN) rate, incidence of axillary nodal metastases, or the number of SLN identified. METHODS: In this prospective multi-institutional study, SLN biopsy was performed on clinical stage T1-2, N0 breast cancer patients using blue dye alone or in combination with radioactive colloid, followed by completion axillary LN dissection. RESULTS: Central tumor location was associated with an improved FN rate, which may be related to reliable drainage from the subareolar lymphatic plexus. Tumor location did not significantly affect the SLN ID rate or the mean number of SLN identified. Medial tumor location was associated with a decreased rate of axillary nodal metastasis. CONCLUSIONS: Breast cancers drain reliably to the axillary lymph nodes regardless of tumor location within the breast.

Axillary lymph node metastasis in stage T1a breast cancer: a pathologic review of 82 patients.

The recent shift toward the diagnosis of smaller breast cancers has led to the reevaluation of their treatment. Because of the low incidence of nodal involvement, recent studies have recommended selective axillary lymph node dissection (AxLND) for early breast cancer. The incidence of nodal involvement is a critical factor in defining the role of AxLND. Large series based on cancer registry data report the incidence of nodal positivity in stage T1a cancer to be 16 to 23 per cent. In contrast, data that include only pathologically reviewed cases report the incidence to be 0 to 6 per cent. We reviewed the medical records of 148 stage T1a breast cancer patients from 1987 through 1994 in two community hospitals as identified by the local tumor registry. After chart review, 115 cases with AxLND underwent pathologic review; 82 were confirmed as stage T1a. Only 3 of 82 (4%) patients were node positive. All three node-positive tumors were of infiltrating ductal histology. No tumor characteristic was predictive of nodal metastasis. Data from the tumor registry and from pathology reports overstated the incidence of nodal involvement (5 and 9%, respectively). In light of the limited clinical benefit and associated cost and morbidity of AxLND, selected informed patients may be spared AxLND.

Image-guided core biopsy has advantages over needle localization biopsy for the diagnosis of nonpalpable breast cancer.

Image-guided core biopsy (IGCB) of nonpalpable mammographic abnormalities has gained attention as an alternative to needle-localized breast biopsy (NLB). This study evaluated IGCB in the diagnostic workup of patients with nonpalpable mammographic lesions suspicious for cancer. Eighty-six patients who underwent IGCB were compared to 85 patients who underwent NLB for the diagnosis of mammographic lesions suspicious for cancer. The incidence of positive margins was less in patients who subsequently underwent needle-localized resection in the IGCB group than in the NLB group (29 and 65%; P < 0.0001). The volume of excision was greater for patients in the IGCB group than for the NLB group (106 cm3 and 52 cm3; P < 0.0001). Patients in the IGCB group averaged 1.1 operative procedures compared with patients in the NLB group, who required an average of 1.9 operative procedures. The mean charge for an IGCB was $1011 compared to $2975 for a NLB. Subset analysis of 32 spiculated masses from the IGCB group and 21 from the NLB group showed similar advantages of IGCB over NLB. The preoperative use of IGCB for mammographically suspicious lesions can reduce the incidence of positive surgical margins and the number of surgical procedures required. The use of IGCB allows for a more efficient diagnostic workup and less expense to the patient.

Accuracy of sentinel lymph node biopsy for patients with T2 and T3 breast cancers.

Although numerous studies have demonstrated that sentinel lymph node (SLN) biopsy can accurately determine the axillary nodal status for early breast cancer some studies have suggested that SLN biopsy may be less reliable for tumors >2 cm in size. This analysis was performed to determine whether tumor size affects the accuracy of SLN biopsy. The University of Louisville Breast Cancer Sentinel Lymph Node Study is a prospective multi-institutional study involving 226 surgeons. The study was approved by the Institutional Review Board of each institution, and informed consent was obtained from all patients. Patients with clinical stage T1-2 N0 breast cancer were eligible for the study. Some patients with T3 tumors were included because they were clinically staged as T2 but on final pathology were found to have tumors >5 cm. This analysis includes 2148 patients who were enrolled from August 1997 through October 2000. All patients underwent SLN biopsy using a combination of radioactive colloid and blue dye injection followed by completion Level I/II axillary dissection. Statistical comparison was performed by chi-square analysis. The SLN identification rate, false negative rate, and overall accuracy of SLN biopsy were not significantly different among tumor stages T1, T2, and T3. We conclude that SLN biopsy is no less accurate for T2-3 breast cancers compared with T1 tumors.

Biological characteristics and biomedical applications of the squid Sepioteuthis lessoniana cultured through multiple generations.

Providing squids--especially their giant axons--for biomedical research has now been achieved in 10 mariculture trials extending through multiple generations. The noteworthy biological characteristics of Sepioteuthis lessoniana are (1) this species is behaviorally and morphologically well suited to the laboratory environment; (2) the life cycle is completed in 4-6 months; (3) growth is rapid (12% and 5% wet body weight d-1 for 100 d and for the life span, respectively), with adult size ranging from 0.4-2.2 kg; (4) feeding rates are high (30% wet body weight d-1), and a variety of live crustaceans and fishes are eaten; (5) crowding is tolerated (about 4 squids m-3); (6) the incidence of disease and cannibalism is low; and (7) reproduction in captivity allows culture through three successive generations. Engineering factors contributed to culture success: (1) physical design (i.e., size, shape, and painted pattern) of the culture tanks; (2) patterns of water flow in the culture tanks; (3) water filtration systems; and (4) spawning substrates. Initial production (a few hundred squids per year) suggests that large-scale culture will be able to supply the needs of the biomedical research community. The size (> 400 microns in diameter) and characteristics of the giant axons of Sepioteuthis are appropriate for experimentation, and other studies indicate that the eye, oculomotor/equilibrium system, olfactory system, blood, and ink are equally suitable for research.

Pharmacokinetics of primaquine in healthy volunteers.

The pharmacokinetics of primaquine were investigated in 8 healthy subjects (4 males and 4 females). The volunteers received 15 mg base of primaquine daily for 14 days. The results showed that the concentration-time profiles in whole blood and in plasma were similar. The mean values (+/- SD) of area under the curve (AUC) of the last dose were significantly decreased when compared to the values of the first dose both in whole blood and in plasma (909.96 +/- 603.07, 1,147.05 +/- 684.8 ng.hr/ml respectively in whole blood with p = 0.007 and 1,255.11 +/- 531.59, 1,603.66 +/- 505.45 ng.hr/ml respectively in plasma with p = 0.023). The decrease in the concentration-time profile of the last dose was due to enhancement of drug elimination with significant increase in clearance after the last dose (4.871 +/- 1.741 and 6.443 +/- 2.514 ml/min/kg respectively in whole blood with p = 0.007, 3.199 +/- 1.197 and 4.422 +/- 2.068 ml/min/kg respectively in plasma with p = 0.016).

Residual feed intake, body composition, and fertility in yearling beef heifers.

One hundred thirty-seven spring-born yearling beef heifers of British breed types were used to determine the relationships between residual feed intake (RFI) and growth rate, body composition, mature size, and fertility. Heifers were housed in a dry lot facility during the experimental period, and data were collected over a 2-yr period (yr 1, n = 67; yr 2, n = 70). Individual feed intake, BW, BCS, hip height, and ultrasonic measurements [subcutaneous rib fat (UBF), rump fat (URF), LM area (LMA), and intramuscular fat (IMF)] of body composition were recorded. Individual feed intakes (kg of TDN consumed/d) were used to calculate RFI combining both years of data. Heifers averaged 387.0 ± 19.4 d of age and 337.1 ± 29.9 kg of BW at initiation of the experiment. Mean ADG was 1.14 ± 0.21 kg/d during the trial. Based on RFI, with year of test and farm of origin included in the model as covariates, heifers were classified into groups: positive (POS; 0.74 kg of TDN/d) or negative (NEG; -0.73 kg TDN/d) for first analysis and high (HI), medium (MED), or low (LO; mean RFI = 1.06, -0.01, and -1.13 kg of TDN/d, respectively) subsequently. An initial phenotypic relationship (P < 0.05) between RFI and both UBF and URF (r = 0.19 and 0.17, respectively) was sustained (P < 0.01) with UBF (r = 0.27) and URF (r = 0.24) to trial conclusion. No other correlations with RFI were significant. Heifers classified as POS reached puberty earlier than those classified as NEG (414 ± 3.83 vs. 427 ± 4.67 d of age, P = 0.03), and possessed greater LMA per 100 kg of BW (LMACWT) at conclusion of the trial (P < 0.01). Medium heifers exhibited less URF (P < 0.05) compared with either HI or LO heifers at trial initiation. Low heifers possessed less LM area (cm(2)) per 100 kg of BW (P < 0.05) than HI but did not differ (P > 0.10) from MED heifers at either the beginning or the end of test. Additionally, a negative linear relationship was observed between RFI and age at puberty (P < 0.05). Each 1-unit increase in RFI corresponded to a decrease of 7.5 d in age at puberty, but did not affect pregnancy or conception rates (P > 0.10). Differences in body fat and rate of metabolism associated with RFI could delay reproductive maturity.