Substituted anilides from chitin-based 3-acetamido-furfural.

The synthesis of aromatic compounds from biomass-derived furans is a key strategy in the pursuit of a sustainable economy. Within this field, a Diels-Alder/aromatization cascade reaction with chitin-based furans is emerging as a powerful tool for the synthesis of nitrogen-containing aromatics. In this study we present the conversion of chitin-based 3-acetamido-furfural (3A5F) into an array of di- and tri-substituted anilides in good to high yields (62-90%) via a hydrazone mediated Diels-Alder/aromatization sequence. The addition of acetic anhydride expands the dienophile scope and improves yields. Moreover, replacing the typically used dimethyl hydrazone with its pyrrolidine analogue, shortens reaction times and further increases yields. The hydrazone auxiliary is readily converted into either an aldehyde or a nitrile group, thereby providing a plethora of functionalized anilides. The developed procedure was also applied to 3-acetamido-5-acetylfuran (3A5AF) to successfully prepare a phthalimide.

Iron Tetrasulfonatophthalocyanine-Catalyzed Starch Oxidation Using H2O2: Interplay between Catalyst Activity, Selectivity, and Stability.

Oxidized starch can be efficiently prepared using H2O2 as an oxidant and iron(III) tetrasulfophthalocyanine (FePcS) as a catalyst, with properties in the same range as those for commercial oxidized starches prepared using NaOCl. Herein, we performed an in-depth study on the oxidation of potato starch focusing on the mode of operation of this green catalytic system and its fate as the reaction progresses. At optimum batch reaction conditions (H2O2/FePcS molar ratio of 6000, 50 °C, and pH 10), a high product yield (91 wt %) was obtained with substantial degrees of substitution (DSCOOH of 1.4 and DSCO of 4.1 per 100 AGU) and significantly reduced viscosity (197 mPa·s) by dosing H2O2. Model compound studies showed limited activity of the catalyst for C6 oxidation, indicating that carboxylic acid incorporation likely results from C-C bond cleavage events. The influence of the process conditions on the stability of the FePcS catalyst was studied using UV-vis and Raman spectroscopic techniques, revealing that both increased H2O2 concentration and temperature promote the irreversible degradation of the FePcS catalyst at high pH. The rate and extent of FePcS degradation were found to strongly depend on the initial H2O2 concentration where also the rapid decomposition of H2O2 by FePcS occurs. These results explain why the slow addition of H2O2 in combination with low FePcS catalyst concentration is beneficial for the efficient application in starch oxidation.

Spin-Crossover in a Pseudo-tetrahedral Bis(formazanate) Iron Complex.

Spin-crossover in a pseudo-tetrahedral bis(formazanate) iron(II) complex (1) is described. Structural, magnetic, and spectroscopic analyses indicate that this compound undergoes thermal switching between an S=0 and an S=2 state, which is very rare in four-coordinate complexes. The transition to the high-spin state is accompanied by an increase in Fe-N bond lengths and a concomitant contraction of intraligand N-N bonds. The latter suggests that stabilization of the low-spin state is due to the π-acceptor properties of the ligand. One-electron reduction of 1 leads to the formation of the corresponding anion, which contains a low-spin (S=1/2) Fe(I) center. The findings are rationalized by electronic structure calculations using density functional theory.

Validation of a nomogram to predict the risk of nonsentinel lymph node metastases in breast cancer patients with a positive sentinel node biopsy: validation of the MSKCC breast nomogram.

BACKGROUND: Completion axillary lymph node dissection (ALND) remains the standard of care for patients with disease-positive sentinel lymph nodes (SLN). However, approximately two-thirds will have no additional disease-positive nodes. To identify the patient's individual risk for non-SLN metastases, the Memorial Sloan-Kettering Cancer Center (MSKCC) developed a nomogram. METHODS: The records of 182 breast cancer patients who underwent SLN and ALND were selected. Serial hematoxylin and eosin (HE) analysis and immunohistochemistry were routinely performed on each sentinel node. For application of the nomogram, the detection method was assigned in two ways: for all metastases visible by serial HE, the method of detection was scored as "serial HE" (method 1), independent of the tumor size, and by a combination of size and staining method (method 2); so macrometastasis were scored as detected by routine HE, micrometastasis by serial HE, and isolated tumor cells by immunohistochemistry. A receiver operating characteristic curve (ROC) was drawn, and the area under the curve was calculated to assess the discriminative power of the nomogram. RESULTS: The area under the ROC was .71 (range, .64-.79) according to method 1 and .75 (range, .67-.88) according to method 2. CONCLUSIONS: Because the variable "method of detection" in the MSKCC nomogram is a surrogate for SLN metastasis size, the size category of the SLN metastasis can be used in applying the nomogram to patients in whom the SLN histologic analysis is performed by a much different procedure than that used to develop the MSKCC nomogram. This results in an improved predictive accuracy.

The value of sentinel lymph node biopsy in ductal carcinoma in situ (DCIS) and DCIS with microinvasion of the breast.

AIM: Ductal carcinoma in situ (DCIS) refers to the preinvasive stage of breast carcinoma and should not give axillary metastases. Its diagnosis, however, is subject to sampling errors. The role of sentinel lymph node biopsy (SLNB) in management of DCIS or DCISM (with microinvasion) remains unclear. The purpose of this study was to review our experience with SLNB in DCIS and DCISM. METHODS: A review of 51 patients with a diagnosis of DCIS (n=45) or DCISM (n=6), who underwent SLNB and a definitive breast operation between January 1999 and December 2006, was performed. RESULTS: In 10 patients (19.6%) definitive histology revealed an invasive carcinoma. SLN (micro)metastases were detected in 5 out of 51 patients, of whom 2 had a preoperative diagnosis of grade III DCIS and 3 of DCISM. Three patients (75%) had micrometastases (< 2 mm) only. In 2 patients, histopathology demonstrated a macrometastasis (> 2 mm). All 5 patients underwent axillary dissection. No additional positive axillary lymph nodes were found. CONCLUSIONS: In case of a preoperative diagnosis of grade III DCIS or a grade II DCIS with comedo necrosis and DCIS with microinvasion, an SLNB procedure has to be considered because in almost 20% of the patients an invasive carcinoma is found after surgery. In this case the SLNB procedure becomes less reliable after a lumpectomy or ablation has been performed. SLN (micro)metastases were detected in nearly 10% of the patients. The prognostic significance of individual tumour cells remains unclear.

Unequivocal morphological diagnosis of fungi in morphologically abnormal nails.

AIMS: To analyse the prevalence of fungi in abnormal nails by morphological diagnosis. Prevalence studies of onychomycoses in temperate climate zones have yielded widely varying rates, possibly reflecting the confounding effects of referral bias, sampling specificity and intrinsic sensitivity of the diagnostic techniques employed. METHODS AND RESULTS: The method employed to identify fungi in nails entailed primary fixation using a non-formaldehyde-based coagulative fixative (BoonFix; Finetec, Japan) and microwave-enhanced processing to histology, followed by staining the paraffin sections with periodic acid-Schiff, using haematoxylin as a routine counterstain. The results of 990 nail samples were tabled for statistical analysis related to gender, patient age and diabetes mellitus status. In four of the 990 (< 1%) analysed cases the diagnosis was found to be equivocal using the method employed. These cases were jointly reviewed for definitive diagnosis. The overall prevalence of invasive hyphal structures was found to be 606/990 (approximately 61%). The relative risk for fungal infection in morphologically abnormal nails was found to be higher for persons < 20 years old or diabetic patients aged > or = 71 years. CONCLUSIONS: The 61% positivity rate for fungi found justifies systematic direct submission of samples from abnormal nails for histological confirmation in order to avoid unwarranted treatment.

[A fatal infection due to avian influenza-A (H7N7) virus and adjustment of the preventive measures]. / Een fatale infectie door aviair influenza-A (H7N7)-virus en aanpassing van het preventiebeleid.

In February 2003, the highly pathogenic avian influenza-A virus, subtype H7N7, was the causative agent of a large outbreak of fowl plague in the Netherlands. Two days after visiting a poultry farm that was infected by fowl plague, a 57-year-old male veterinarian developed malaise, headache and fever. After 8 days he was admitted to hospital with signs of pneumonia. Five days later, his condition deteriorated alarmingly. Despite extensive pharmacotherapy he died 4 days later of acute pneumonia. Influenza-A virus, subtype H7N7, was identified by means of reverse transcriptase/PCR in broncho-alveolar washings that had been obtained earlier; routine virus culture yielded the isolate A/Nederland/219/03, which differs by 14 amino-acid substitutions from the first isolate in a chicken (A/kip/Nederland/1/03). Partly as a result of this case, the preventive measures were then adjusted; people who came into contact with infected poultry were given increased possibilities for vaccination and the administration of oseltamivir.

[Persistent infiltrative pulmonary disease]. / Persisterende infiltratieve longafwijkingen.

Two patients, a woman aged 63 and a man aged 64 years, were admitted with pulmonary complaints and persistent infiltrative lung abnormalities as revealed in chest X-rays. Routine diagnostic analysis did not lead to a diagnosis. However, a pathological examination of biopsies acquired by means of video-assisted thoracoscopic surgery (VATS), revealed bronchiolitis obliterans organising pneumonia (BOOP). In the first patient the BOOP manifested itself as a rapidly progressive disease with fever, pulmonary complaints and X-ray abnormalities. There was no response to standard antibiotic treatment. The other patient had suffered from rheumatoid arthritis for a considerable time and gradually developed BOOP. Both patients recovered following adequate therapy with high doses of oral corticosteroids. BOOP is a pathological-anatomical entity. It is a nonspecific excessive repair response to a variety of stimuli, such as infection, drugs, collagen vascular diseases, inflammatory disorders, transplantation, intoxication and irradiation. BOOP can also occur idiopathically. A high-resolution CT-scan is useful in distinguishing BOOP from interstitial pulmonary fibrosis and other interstitial lung diseases. An open lung biopsy is necessary for the diagnosis BOOP and is best performed by means of VATS. The treatment of BOOP consists of administering high doses of corticosteroids (prednisone 1 mg/kg/day) and if treated adequately, the prognosis is fairly good. Due to the extensive variety in aetiology, the specific diagnostic procedures and the good response to necessary treatment, BOOP should be considered in the differential diagnosis of patients with persistent infiltrative lung disease.

[Objective re-evaluation procedures in cases of possible diagnostic error]. / Naar een objectieve herbeoordelingsprocedure bij een mogelijke diagnostische dwaling.

Auxiliary diagnostic specialists such as clinical pathologists or radiodiagnosticians may be held liable by injured patients for erroneous diagnoses. Nearly always there will be a reconstruction of the situation in which the alleged misstake was made, and relevant facts will be tested against both professional and legal rules. The Court or one of the parties involved frequently ask an expert for re-evaluation of microscopic preparations, X-rays, etc. This objectivating evaluation requires a procedure that does justice to the original diagnostic situation and therefore should not be made by one single expert familiar with the chain of events. The results of the re-evaluation should be interpreted meticulously and their relative importance established by the Court.

Cerebral hemorrhagic infarction at autopsy: cardiac embolic cause and the relationship to the cause of death.

In 48 patients dying within 15 days following a supra-tentorial cerebral infarct, the presence of hemorrhagic infarction at autopsy was related to a cardiac embolic cause of the infarct, and to the cause of death. Hemorrhagic infarcts were more common among patients dying from brain herniation than among those dying from a non-cerebral cause. Cardiac embolic strokes were more often hemorrhagic at autopsy than strokes without such cause; this could be explained by a significant higher rate of brain herniation and death after embolic stroke. On the other hand infarcts with extended hemorrhages more often tended to have a cardiac than a non-cardiac cause. These data, together with earlier clinical findings suggest that autopsy studies are biased in relating hemorrhagic infarction almost exclusively to a cardiac embolic cause of stroke, although cardiac emboli may produce more extended hemorrhages.

The serological relationship of herpesvirus ovis to other herpesviruses and its possible involvement in the aetiology of jaagsiekte.

Cross-neutralization studies showed that 3 different isolates of herpesvirus ovis from cell cultures derived from the lungs of sheep suffering from jaagsiekte were not only identical but were also related to similar isolate made in Scotland. No relationship, however, could be established between herpesvirus ovis and common bovine or equine herpesviruses. Antibodies to herpesvirus ovis were present in roughly 70% of all animals tested and no evidence was obtained for the involvement of the virus in the aetiology of jaagsiekte. On the other hand, the absence of antibodies in sheep sera from Iceland as well as the other data obtained in this study did not exclude involvement of the virus in jaagsiekte.

Immunosuppression in new-born lambs.

A novel technique, based on cytotoxicity-neutralization, was developed for the in vitro titration of anti-sheep lymphocyte and anti-sheep macrophage sera. The titres obtained for a number of antisera were compared with those found in an agglutination assay. Anti-lymphocyte sera with a high cytotoxicity-neutralization titre very effectively suppressed the number of circulating lymphocytes in the peripheral blood of treated new-born lambs, thus indicating in vivo immunosuppressive activity.