Uveal melanoma: correlation of histopathologic and radiologic findings by using thin-section MR imaging with a surface coil

PURPOSE: To evaluate whether the different signal intensities at magnetic resonance (MR) imaging of melanoma are associated with a higher content of melanin. MATERIALS AND METHODS: In a prospective study, MR imaging and ophthalmoscopic examination findings in 42 patients (19 women, 23 men; age range, 30-87 years) with uveal melanoma were compared with histopathologic examination findings obtained after enucleation. MR imaging was performed with 2-mm sections by using a 5-cm surface coil. T1- and T2-weighted images were obtained before and after contrast material administration. RESULTS: In 33 (79%) of the patients, there was homogeneous tumor pigmentation, whereas in nine (21%) patients, there was inhomogeneous bipartite tumor pigmentation. Compared with the histopathologic data, the results of qualitative evaluation were accurate in 29 (58%) of 50 and in 26 (53%) of 49 tumorous areas on T1- and T2-weighted images, respectively. Quantitative evaluation yielded better results, especially at T1-weighted imaging; an 86% correlation was found. Because of methodological reasons, only the superficial pigmentation of inhomogeneous tumors could be evaluated with ophthalmoscopy. CONCLUSION: Thin-section MR imaging of the eye enables an accurate prediction of melanomatous pigmentation with quantitative evaluation of plain T1-weighted images and is superior to ophthalmoscopy in cases of inhomogeneous pigmentation.     

Evaluation of polyurethane stent implantation for the treatment of complete obstruction of the nasolacrimal system: 8-month follow-up and complications

Dacryocystorhinostomy is still the standard procedure complete stenosis of the nasolacrimal duct. New methods try to preserve the natural lacrimal pathway. Song implanted in 1995 a nasolacrimal polyurethane stent through the nasolacrimal duct. The results and complications of this new method are described in this prospective study. METHODS: Thirty consecutive patients with complete obstruction of the nasolacrimal duct or lacrimal sac were included in the study. The stenosis was localized by dacryocystography. The ages ranged from 22 to 87 years (mean, 58.9 +/- 16 years). Dacryocystography was performed immediately, 4 weeks and 8 months after the procedure to verify the position and patency of the stent. RESULTS: Twenty-five short (35 mm) and 5 long (45 mm) stents were implanted. Twenty-four of 30 patients after 4 weeks and 9 of 10 patients after 8 months had reduced or no complaints. In 1 patient the stent was obstructed. Forceful irrigation with saline solution permitted recanalization. In 1 patient the stent had moved into the upper canaliculus. Because of irritation of the canaliculus it had to be pulled out after 2 months. CONCLUSION: The follow-up is still too short to recommend stent implantation as a real alternative to dacryocystorhinostomy. The main advantages are that the procedure is faster, no incision is necessary, and the local anesthesia is easier. The disadvantage is the need for X-ray examination.     

Urine test strips: reliability of semi-quantitative findings under tropical conditions

Semi-quantitative urinalysis with urine reagent strips (URS) for erythrocyturia (EU), leucocyturia (LU) and proteinuria (PU) was performed in Congolese and Sudanese school children withSchistosoma haematobium and/orS.mansoni infection. Quantitative urinalysis was performed on the same specimen using microscopy and a Neubauer counting chamber for EU and LU and the Coomassie blue dye-binding assay for PU. Microscopically detectable EU of more than 10 cells/l was found in 63% of all samples and LU of more than 20 cells/l was found in 60% of all samples. With the Coomassie blue method, PU of more than 150 mg/l was detected in 51% of all samples. URS gave positive results of grade 1–3 for EU in 69% of all samples, for LU in 63% of all samples and for PU in 66% of all samples. The sensitivity and specificity of URS compared with standard reference methods were as follows: EU 95% and 75%, LU 81% and 81% and PU 90% and 56%. When the results of all three test were combined, URS differentiated abnormal from normal urine specimens with a sensitivity of 94% and a specificity of 70%. Median quantitative results showed a good correlation with semiquantitative URS readings for all parameters, but there was a wide range of URS scores.We concluded that URS sensitively detect urinary abnormalities and thus may be used as a general screening method under field conditions when more specific methods cannot be performed. In the hospital laboratory,urine microscopy with a counting chamber would be preferred to URS as a sole method for EU and LU detection; URS is useful for the detection of PU in the tropical hospital laboratory where an appropriate quantitative method with a better specificity may not be available.     

The composite solubility versus pH profile and its role in intestinal absorption prediction

The purpose of this study was to examine absorption of basic drugs as a function of the composite solubility curve and intestinally relevant pH by using a gastrointestinal tract (GIT) absorption simulation based on the advanced compartmental absorption and transit model. Absorption simulations were carried out for virtual monobasic drugs having a range of pKa, log D, and dose values as a function of presumed solubility and permeability. Results were normally expressed as the combination that resulted in 25% absorption. Absorption of basic drugs was found to be a function of the whole solubility/pH relationship rather than a single solubility value at pH 7. In addition, the parameter spaces of greatest sensitivity were identified. We compared 3 theoretical scenarios: the GIT pH range overlapping (1) only the salt solubility curve, (2) the salt and base solubility curves, or (3) only the base curve. Experimental solubilities of 32 compounds were determined at pHs of 2.2 and 7.4, and they nearly all fitted into 2 of the postulated scenarios. Typically, base solubilities can be simulated in silico, but salt solubilities at low pH can only be measured. We concluded that quality absorption simulations of candidate drugs in most cases require experimental solubility determination at 2 pHs, to permit calculation of the whole solubility/pH profile.     

Kinetic versus thermodynamic factors in calcium renal lithiasis

Calcium renal lithiasis formation depends on the balance between thermodynamic (supersaturation) and kinetic (inhibitors, nucleants)factors. In this paper, the importance of both groups was evaluated using(a) the complete urine analysis data obtained from 32 healthy volunteers and 141 active stone-formers, and (b) a comprehensive computer model to calculate the supersaturation values of calcium oxalate monohydrate,hydroxyapatite and brushite in each urine sample. The results of this evaluation were used to assess the possible effectiveness of a given pharmacological treatment. This revised version was published online in August 2006 with corrections to the Cover Date.     

Circulating growth factor levels are associated with tumorigenesis in neurofibromatosis type 1.

PURPOSE: Neurofibromatosis type 1 (NF1) is characterized by systemic development of neurofibromas. Early clinical diagnosis can be ambiguous, and genetic diagnosis can be prohibitively difficult. Dysregulation of a number of growth factors has been suggested to be a mechanism of pathogenesis. This study was performed to assess the contribution of circulating growth factors for diffuse tumorigenesis and the diagnostic value of circulating growth factor identification in serum. EXPERIMENTAL DESIGN: The growth stimulation of neurofibroma-derived cells by serum from NF1 patients was tested, and serum growth factor levels in a cohort of NF1 patients (n = 39) between the ages of 7 and 70 years were analyzed. RESULTS: Concentrations of midkine (MK) and stem cell factor, but not epidermal growth factor, were substantially increased in serum of NF1 patients when compared with healthy controls. Within the NF1 group, MK levels increased dramatically at puberty from an average of 0.79 ng/mL in patients <18 years to 1.18 ng/mL in patients >18 years old. Stem cell factor and MK concentrations above a defined threshold in serum of NF1 patients are of diagnostic benefit for 96% of patients in the cohort tested. Furthermore, serum from NF1 patients enhanced proliferation of human neurofibroma-derived primary Schwann cells and endothelial cells substantially better than normal serum. CONCLUSIONS: Enhanced circulating growth factor levels contribute to diffuse tumorigenesis in NF1 and may provide the basis for molecular diagnosis.     

Hypoglycemic effects of steroidal sapogenins isolated from Jamaican bitter yam, Dioscorea polygonoides.

In this study, three steroidal sapogenins (Delta3 diosgenin, diosgenin, and pennogenin) and the phytosterols, stigmasterol and beta-sitosterol were isolated from Jamaican bitter yam, Dioscorea polygonoides. Their effects on fasting blood glucose and intestinal amylase and ATPases in streptozotocin-induced diabetic rats were studied. The diabetic rats (fed supplemented and unsupplemented diets) lost weight significantly compared to the normal group. There was a significant increase in the activity of alpha-amylase in the proximal region of the small intestinal mucosa of diabetic rats fed sapogenin extract or commercial diosgenin. However, this did not result in increased fasting blood glucose. Instead, supplementation of the diet with bitter yam sapogenin extract significantly decreased fasting blood glucose compared to the diabetic group. Supplementation of the diet with bitter yam sapogenin extract or commercial diosgenin significantly reduced Na+-K+-ATPase activity in all three regions compared to the diabetic control group. Commercial diosgenin supplementation resulted in a significant increase in Ca2+ ATPase activity in proximal region compared to the diabetic control and bitter yam sapogenin extract groups. The effect of bitter yam sapogenin extract or commercial diosgenin on intestinal Na+-K+-ATPase activity could account for their hypoglycemic properties. However, there was adverse effect on the body weight.     

Metabolism and disposition of imatinib mesylate in healthy volunteers.

Imatinib mesylate (GLEEVEC, GLIVEC, formerly STI571) has demonstrated unprecedented efficacy as first-line therapy for treatment for all phases of chronic myelogenous leukemia and metastatic and unresectable malignant gastrointestinal stromal tumors. Disposition and biotransformation of imatinib were studied in four male healthy volunteers after a single oral dose of 239 mg of (14)C-labeled imatinib mesylate. Biological fluids were analyzed for total radioactivity, imatinib, and its main metabolite CGP74588. Metabolite patterns were determined by radio-high-performance liquid chromatography with off-line microplate solid scintillation counting and characterized by liquid chromatography-mass spectrometry. Imatinib treatment was well tolerated without serious adverse events. Absorption was rapid (t(max) 1-2 h) and complete with imatinib as the major radioactive compound in plasma. Maximum plasma concentrations were 0.921 +/- 0.095 mug/ml (mean +/- S.D., n = 4) for imatinib and 0.115 +/- 0.026 mug/ml for the pharmacologically active N-desmethyl metabolite (CGP74588). Mean plasma terminal elimination half-lives were 13.5 +/- 0.9 h for imatinib, 20.6 +/- 1.7 h for CGP74588, and 57.3 +/- 12.5 h for (14)C radioactivity. Imatinib was predominantly cleared through oxidative metabolism. Approximately 65 and 9% of total systemic exposure [AUC(0-24 h) (area under the concentration time curve) of radioactivity] corresponded to imatinib and CGP74588, respectively. The remaining proportion corresponded mainly to oxidized derivatives of imatinib and CGP74588. Imatinib and its metabolites were excreted predominantly via the biliary-fecal route. Excretion of radioactivity was slow with a mean radiocarbon recovery of 80% within 7 days (67% in feces, 13% in urine). Approximately 28 and 13% of the dose in the excreta corresponded to imatinib and CGP74588, respectively.