Dissolution kinetics of paracetamol single crystals

The dissolution anisotropy of paracetamol crystals grown in the presence and absence of the molecularly similar additive, p-acetoxyacetanilide (PAA) was studied under controlled conditions using a single crystal dissolution method in undersaturated aqueous solutions. Linear dissolution rates were determined for all the major habit faces by measuring their movement (regression) with time in a flow cell using a microscope. The rates of dissolution of particular faces of the pure material were distinctly different in crystals of different morphology grown at different supersaturations. The dissolution rates of [001] and [110] faces of crystals grown in the presence of PAA (6.02% w/w in solution) are higher than those of pure paracetamol. The results correlate with the distribution of strain in the crystal and support the concept that integral strain increases the solubility and hence the dissolution rate of the material. The mechanism of the dissolution process at the [001], [201;] and [110] faces was defined using optical microscopy and X-ray topography. At all undersaturations above 1% the dissolution studies yielded well developed, structurally oriented, etch pits on both [001] and [201;] faces while on the [110] face rough shallow etch pits were observed. On all three faces, this etch-pitting was considerably more widespread than the dislocation content of the sector and probably reflects a 2-dimensional nucleation process rather than a dislocation controlled mechanism.     

Cryotherapeutic ablation of liver tumours

BACKGROUND: This paper reports a 7-year experience of cryoablation for colorectal and non-colorectal liver metastases. METHODS: A retrospective review was undertaken of patients treated in two adjacent UK centres in the north-west of England. RESULTS: Over a 7-year period (1993-2000), 57 patients underwent cryotherapy for malignant hepatic tumours (41 colorectal, 16 non-colorectal). In the patients with colorectal metastases, preoperative carcinoembryonic antigen (CEA) levels fell significantly, from a mean of 444.1 to 6.22 micro g/l (P = 0.002). One patient died, two developed cryoshock and six had cardiorespiratory complications. All patients with colorectal metastases subsequently received 5-fluorouracil-based chemotherapy. The remaining 16 patients with non-colorectal tumours (seven neuroendocrine metastases, five hepatocellular carcinomas, three sarcomas, one cholangiocarcinoma) all received cryotherapy alone, with no major complications. The median survival for patients with non-colorectal metastases was 37 months, compared with 22 months for those with colorectal metastases (P = 0.005). CONCLUSION: Hepatic cryotherapy is effective and safe, as demonstrated by the significant reduction in postoperative CEA concentration and the low risk of complications. However, this initial short-term success was not reflected in 5-year survival rates. Cryotherapy for non-colorectal metastases had a greater long-term survival benefit and is a useful means of controlling symptoms.     

A probability prediction rule for malignant cervical lymphadenopathy using sonography

BACKGROUND: Our purpose was to weigh various sonographic parameters as predicting malignant cervical lymphadenopathy and build a reliable prediction rule. METHODS: One hundred and eighty-nine cervical lymph node lesions from 125 consecutive patients were used for building the prediction model. Sonographic variables, including 15 morphologic features of B-mode, 5 vascular parameters of color Doppler mode, along with age and sex, were analyzed with multivariate logistic regression to evaluate the joint effect of a set of independent variables. A prediction rule for malignant lymphadenopathy was established, and prospective validation was assessed on a new group consisting of 100 lymph nodes from another 60 consecutive patients. RESULTS: The association of heterogeneous content, long transverse diameter, pathologic vascular pattern, high vascular density, and older age provided the most robust prediction value. Scoring scale was designed as 1x (age) + 2x (vascularity index) + 3x (short axis) + 4x (vascular pattern) + 4x (internal echo) according to the parameter estimates of multivariate logistic regression analysis. Cut-off value of score >==10 as malignancy resulted in 89.2% sensitivity and 85.2% specificity. Prospective validation also showed satisfactory results (sensitivity, 82.9%; specificity, 86.2%). CONCLUSIONS: By measuring only 4 sonographic parameters and age, this prediction rule could provide the physician a nonconfusing and reliable probability reference for managing cervical lymphadenopathy.     

Protective drugs in acute large-dose exposure to organophosphates: a comparison of metoclopramide and tiapride with pralidoxime in rats

Weak and reversible inhibitors of cholinesterase(s), when coadministered in excess with a more potent inhibitor such as organophosphates, can act in a protective manner. The benzamide compound, metoclopramide, confers some protection (putatively via this mechanism) for cholinesterases against inhibition by paraoxon both in vitro and in vivo, after chronic small-dose exposure. Tiapride is a related benzamide. In this study, we compared the protection by metoclopramide and tiapride in rats acutely exposed to large doses of paraoxon with the therapeutic "gold standard," pralidoxime. Group 1 received 1 micromol paraoxon (approximately 75% lethal dose), Group 2 received 50 micromol metoclopramide, Group 3 received 50 micromol tiapride, Group 4 received 50 micromol pralidoxime, Group 5 received 1 micromol paraoxon + 50 micromol metoclopramide, Group 6 1 micromol paraoxon + 50 micromol tiapride, and Group 7 1 micromol paraoxon + 50 micromol pralidoxime. All substances were administered intraperitoneally. The animals were monitored for 48 h and mortality was recorded at 30 min, 1, 2, 3, 4, 24, and 48 h. Blood was taken for red blood cell acetylcholinesterase measurements at baseline, 30 min, 24, and 48 h. With the exception of Group 7, in which some late mortality was observed, mortality occurred mainly in the first 30 min after paraoxon administration with minimal changes occurring thereafter. Mortality at 30 min was 0% in the metoclopramide, tiapride, and pralidoxime groups and 73 +/- 20 (paraoxon), 65 +/- 15 (paraoxon + metoclopramide), 38 +/- 14 (paraoxon + tiapride), and 13 +/- 19 (paraoxon + pralidoxime). Mortality at 48 h was 75 +/- 18 (paraoxon), 67 +/- 17 (paraoxon + metoclopramide), 42 +/- 16 (paraoxon + tiapride), and 27 +/- 24 (paraoxon + pralidoxime). Metoclopramide does not significantly influence mortality after acute large-dose paraoxon exposure. Both tiapride and pralidoxime significantly decreased mortality in our model. The protection conferred by tiapride was significantly less than that conferred by pralidoxime at 30 min, but was not significantly different at 24 and 48 h.     

Mycotic Common Iliac Artery Aneurysm Complicating Methicillin-Resistant Staphylococcus aureus Bacteremia: An Unusual Cause of Ureteric Obstruction

A 60-year-old man presented with ureteric obstruction secondary to a mycotic right common iliac artery aneurysm complicating methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. The diagnosis of MRSA was not known at the time of surgery, and in situ replacement of the aneurysm using a rifampicin-bonded prosthesis was performed. The patient made a full recovery, and to date there is no evidence of residual or recurrent infection. To our knowledge, this is the first reported case of mycotic iliac aneurysm infected with MRSA in the literature. We discuss the consequences and the considerable diagnostic and therapeutic problems that arise. Presented at the Fifty-third International Congress of the European Society for Cardiovascular Surgery, Ljubljana, Slovenia, June 2-5, 2004.