Suspected cresol poisoning in cattle presented for slaughter

Cresol poisoning was suspected in agroup of cattle presented for slaughter at a federaly inspected plant in Illinois. Four cattle died shortly after being unloaded at the slaughter facility, while another animal died after being returned to the feedlot of origin in Iowa. The clinical signs in the affected cattle were lethargy, depression, ataxia, leg weakness, sternal recumbency, dehydration, and severe bloating. Metacresol (3-methyl phenol), commonly found in disinfectants used to clean and sanitize farm equipment and barns, was detected in rumen content from 4 necropsied animals ranging from 25.3 to 52.6 ppm. The exact source of exposure was not identified, but was probably accidental on the farm of origin or on the trailers used for animal transit to the slaughter plant.     

Antitumor agents. 1. Synthesis,biological evaluation,and molecular modeling of 5H-pyrido[3,2-a]phenoxazin-5-one,a compound with potent antiproliferative activity

The iminoquinone is an important moiety of a large number of antineoplastic drugs and plays a significant role in the nucleus of actinomycins, powerful, highly toxic, natural antibiotics that target DNA as intercalating agents. A series of polycyclic iminoquinonic compounds, 2-amino-3H-phenoxazin-3-one (1), 2-amino-1,9-diacetyl-3H-phenoxazin-3-one (2), 2-acetylamino-3H-phenoxazin-3-one (3), 3H-phenoxazin-3-one (4), 5H-pyrido[3,2-a]phenoxazin-5-one (5), and 5H-pyrido[3,2-a]phenothiazin-5-one (6), strictly related to the actinomycin chromophore, were synthesized for developing new anticancer intercalating drugs. The antiproliferative activity of these compounds, evaluated against representative human liquid and solid neoplastic cell lines, showed that 5 and its isoster 6 were the most active compounds inhibiting cell proliferation in a submicromolar range. Compound 5 was also evaluated against KB subclones (KBMDR, KB7D, and KBV20C), which overexpress the MDR1/P-glycoprotein drug efflux pump responsible for drug resistance. All the above KB subclones did not show altered sensitivity to the antiproliferative activity of 5. UV-vis and (1)H NMR spectroscopy experiments support the phenoxazinone 5/DNA binding. Molecular mechanics methods were used to build a three-dimensional model of the 5/[d(GAAGCTTC)]2 complex. Electrostatic interactions between the hydrogen of the positively charged pyridine nitrogen of 5 and the negatively charged oxygen atoms (O4' and O5') of the cytosine C5 residue together with stacking forces contribute to the high antiproliferative activity. The metal(II)-assisted synthesis procedure of 5 is described, and the formation mechanism is proposed.     

Platelet activation markers in patients with nephrotic syndrome. A comparative study of different platelet function tests

BACKGROUND/AIM: Enhanced platelet reactivity may play a significant role in the genesis of the hypercoagulable state of nephrotic syndrome. However, the role of platelet function testing in nephrosis is controversial, partly because the methods used to assess platelet function (platelet aggregation and immunoassays of plasma beta-thromboglobulin and platelet factor 4) have such marked methodological problems. In the present study, we evaluated several tests assessing platelet function in 18 adult patients with idiopathic nephrotic syndrome and normal renal function. METHODS: Platelet function was assessed by measurement of plasma beta-thromboglobulin (enzyme-linked immunosorbent assay, ELISA), plasma P-selectin (ELISA), circulating platelets exposing the activation-dependent antigens P-selectin (CD62P) and lysosomal GP53 (CD63) (flow cytometry), and by aggregation response to agonists such as ADP and collagen. Results were compared to those obtained in a group of 16 age- and gender-matched healthy subjects. RESULTS: Levels of plasma beta-thromboglobulin (p = 0.001), plasma P-selectin (p < 0.001), and CD62P/CD63-positive platelets (p < 0.001 for both) were increased in nephrotic patients as compared to healthy controls. Platelet hyperaggregability in vitro was found in 13/18 patients. The reproducibility of platelet activation markers, as assessed by blood sample collection a week later from all patients, was found to be higher for plasma P-selectin (Spearman correlation coefficient, R = 0.99) and circulating activated platelets (CD62P: R = 0.97; CD63: R = 0.96) than for plasma beta-thromboglobulin (R = 0.78). CONCLUSIONS: Pronounced platelet activation takes place in nephrotic syndrome and may contribute to the hypercoagulability of nephrosis. Whole blood flow cytometry assay of platelet activation and plasma P-selectin assay may represent useful tests to assess the hypercoagulable state in nephrotic patients.     

Impact of preoperative locoregional chemotherapy with fluorodeoxyuridine on the outcome of liver resection

The aim of the study was to evaluate the effects of preoperative intra-arterial hepatic chemotherapy (IAHC) on the outcome of liver resections for hepatic metastases from colorectal cancer. Twelve patients (IAHC group) treated by IAHC with fluorodeoxyuridine (FUdR) and subsequent liver resection and 40 patients who underwent liver resection without preliminary IAHC (non-IAHC group) were analysed comparatively in terms of age, gender, concomitant diseases, previous abdominal surgery, type of hepatic resection, use of portal clamping, and associated surgical procedures. For the purposes of the study, length of operation, intraoperative blood losses, perioperative transfusions, length of hospitalisation, complications and mortality were also recorded. The two groups were comparable (p = n.s.) for those variables affecting the perioperative course. As regards the end points of the study, no significant differences were recorded in length of operation, intraoperative blood losses, perioperative transfusions [except for more postoperative plasma transfusions in the IAHC group (16.7% vs 5.0%, p = 0.009)] and postoperative complications (9.1% vs 17.5%, p = 0.415). Postoperative mortality consisted in one patient in the IAHC group. Postoperative hospitalization was significantly longer in the non-IAHC group (median: 8 vs 10, range: 6-13 vs 5-33 days; p = 0.004). IAHC does not negatively affect the outcome of subsequent liver resection.     

Frequent low penetrance mutations in the Lamin A/C gene,causing Emery Dreifuss muscular dystrophy

Emery Dreifuss muscular dystrophy is a genetically heterogeneous disorder characterized by the clinical triad of early onset contractures, progressive muscular wasting and weakness with humeroperoneal distribution and cardiac conduction defects. Mutations in the Lamin A/C (LMNA) gene are responsible for the autosomal dominant and the autosomal recessive forms. Familiar and sporadic patients carrying mutations in the LMNA gene show high variability in the clinical symptomatology and age of onset. In this report, we describe four families harboring missense mutations in the LMNA gene and we show that the effect of mutations ranges from silent to fully penetrant. We suggest that incomplete penetrance of dominant mutations in the LMNA gene is a common feature and we emphasize the significance of mutational analysis in relatives of sporadic cases of laminopathies, as asymptomatic carriers face high risk of sudden cardiac death.     

Parotid localized Castleman’s disease and HHV-8 infection: a case report

Castleman’s disease (CD) is an unusual massive proliferation of lymphoid tissue distinct in two clinical forms, localized and multicentric. The multicentric form has been related to human herpesvirus 8 (HHV-8), especially in HIV-infected patients, whereas the localized form of CD is still unrelated to viral pathogens. We report a case of a HIV-negative 16-year-old male referred to our hospital with a 12-month history of a painless swelling in his right parotid region. A parotidectomy was performed, and histological analysis evidenced a localized CD. The search for HHV-8 revealed an active virus infection. The patient was commenced on corticosteroid therapy and a follow-up was performed every 6 months. The patient was commenced on corticosteroid therapy and there has been no recurrence after 24 months. The authors report a case of localized parotid CD in a patient with evidence of an active HHV-8 infection. The results of this study does for the first time suggest an association between HHV-8 and localized CD in HIV-negative subjects.     

Concurrent adjuvant chemotherapy and immediate breast reconstruction with skin expanders after mastectomy for breast cancer

Background. Immediate breast reconstruction (IBR) by means of skin expander is currently one of the most widely used methods of breast reconstruction in mastectomized patients. However, given that many breast cancer patients usually receive adjuvant chemotherapy, the adoption of IBR raises new questions concerning possible cumulative toxicity. The present study reports our experience in the use of concurrent adjuvant chemotherapy and immediate breast reconstruction with skin expander after mastectomy for breast cancer and the acute cumulative toxicity of the treatments. Methods. We evaluated a consecutive series of 52 breast cancer patients who have received IBR by skin expander after radical mastectomy and adjuvant chemotherapy concurrently during skin expansion between 1995 and 1998 (IBR/CT group). We identified two series of control patients treated during the same period: 51 consecutive patients undergoing radical mastectomy and IBR without adjuvant chemotherapy (IBR group) and 63 consecutive patients undergoing radical mastectomy and adjuvant chemotherapy without IBR (CT group). For each patient, we evaluated the incidence of surgical complications and chemotherapy's side effects and dose intensity. Results. The interval between surgery and the start of expander inflation was similar in IBR/CT (range 0–19, median 5 days) and IBR groups (range 0–40, median 5 days) and the timing of inflation was not influenced by chemotherapy. The overall incidence of surgical complications in patients undergoing IBR was low: seroma in eight cases, infection in one, skin necrosis in one, expander rupture in two and erythema in three. There were no statistically significant differences in the distribution of complications between the IBR/CT and IBR groups. The dose intensity of chemotherapy was similar between IBR/CT and CT groups, with a median dose intensity of 96% and 95% of the projected dose, respectively. The only statistically significant difference in terms of chemotherapy side effects (p=0.03) was that stomatitis was more frequent and intense in the CT than in the IBR/CT group. Conclusions. Concurrent treatment with IBR and adjuvant chemotherapy appears feasible and safe, it does not increase acute surgical complications or chemotherapy side effects, and does not require any changes in dose intensity or the timing of inflation.     

Is there an association between alcohol intake or smoking and small bowel adenocarcinoma? Results from a European multi-center case–control study

Objective:To discover whether tobacco smoking and intake of different types of alcoholic drinks are associated with small bowel adenocarcinoma (SBA). Methods:A population-based European multi-center case–control study was conducted from 1995 to 1997. Results:After a histological review using uniform diagnostic criteria, 47 (33%) of the 142 identified cases of SBA were excluded due to reclassification as either tumors of the papilla of Vater (n = 22), stromal tumors, or metastases; 95 cases were accepted for study. In all, 70 cases of SBA together with 2070 controls matched by age, sex, and region were interviewed. A high intake (more than 24 g alcohol per day) of beer or spirits was associated with SBA, an odds ratio (OR) of 3.5 and 95% confidence intervals (CI) of 1.5–8.0 and 3.4 (95% CI 1.3–9.2), respectively). There was no association with wine intake or total alcohol intake. Tobacco smoking was probably unrelated to SBA. Conclusions:A high intake of beer or spirits seems to be a risk factor for SBA. Since this association was not seen for wine drinkers, protective components of wine may counterbalance a carcinogenic effect of alcohol on the small bowel. Alternatively, the result may be confounded by other factors, e.g. dietary factors.