Cutaneous angioleiomyoma

Leiomyomas are smooth-muscle tumors that may be encountered in the practice of podiatric medicine when they affect the arrector pili muscles or the smooth muscle of a vessel wall. In the present case, the lesion was located on the heel, an area with no hair growth; this further supports the diagnosis, as the most likely origin of the lesion was the smooth muscle of a blood vessel. Vascular leiomyomas show a greater predilection for the lower extremities than their superficial counterparts. Surgical excision is the treatment of choice for these benign lesions, whose prognosis is excellent. When a patient presents with a painful mass in the lower extremity, the diagnosis of leiomyoma should be considered.     

Critical review of 215 cases of non-palpable mammary lesions]

PURPOSE: The natural history of human breast cancer shows that lesion size correlates directly with nodal metastases and distant spread. Nodal metastases are found in only 6% of cases in the preclinical stage of the tumor and therefore imaging must detect a breast cancer before it becomes palpable. We reviewed 215 nonpalpable breast lesions studied in the last 10 years to assess observers performance and ultimately improve the interpretation of suspicious mammograms, evaluating "cost" in terms of the ratio between benign and malignant lesions (B/M). MATERIAL AND METHODS: From 1988 to October 1998, two hundred and fifteen women with nonpalpable breast lesions suspected at mammography were examined. The lesions were removed after stereotaxic or US location and a radiograph of the surgical specimen was always performed. Mammographic patterns were interpreted retrospectively by two blinded radiologist experienced in breast imaging and specialized in locating nonpalpable breast lesions. Mammographic patterns were classified as poorly/highly suspicious calcifications, regular/irregular masses, spiculated masses, masses with calcifications and parenchymal distortions. Radiographic findings were compared with surgical results and the data used to calculate the B/M, positive predictive value (PPV) for malignancy and the trend of operator's performance. RESULTS: Modern techniques permit to detect a very high number of in situ breast carcinomas. Nineteen of 22 lesions (86%) were detected by mammography as highly suspicious calcifications, 2/22 as spiculated masses and 1/22 as a mass with calcifications. No in situ carcinoma was detected as an irregular mass. All regular masses were proven to be benign at histology. B/M analysis showed a decreasing trend (from 1.94 in the first 3 years to .57 in 1994-96, to .83 in 1997-98) and an overall value of .90. The PPV for malignancy was 83.33% for spiculated masses, 65.5% for highly suspicious calcifications, 63.63% for irregular masses, 47.05% for masses with more or less dysmorphic calcifications, 32.65% for poorly suspicious calcifications, 8.33% for parenchymal distortions and 0% for regular masses. DISCUSSION AND CONCLUSIONS: All spiculated masses and highly suspicious calcifications and microcalcifications should be removed. Biopsy is recommended in parenchymal distortions, despite its low predictive value for malignancy, because these lesions are uncommon and the cost of biopsy is therefore acceptable. Needle aspiration or long-term monitoring can be reconsidered for irregular masses and poorly suspicious microcalcifications. Finally, relative to possible different interpretations of mammographic patterns by center and operator's experience, we suggest that the PPV for every single pattern be continually reassessed based on personal case records rather than on literature data. This holds true especially for microcalcifications.     

A comparison of electrophysiological tests for the early diagnosis of diabetic neuropathy

Clinical criteria and several electrophysiological parameters for detecting nerve damage were compared in 99 patients with diabetes mellitus type 1 and type 2. Abnormal results were found in sural/radial amplitude ratio (51%), minimal F-wave latency of the tibial nerve (36.4%), sensory conduction velocity of the sural nerve (29.8%), and sural sensory nerve action potential amplitude (29.3%) when pooling data from all patients and comparing them to age- and height-matched normal control subjects. Analysis of all the parameters revealed large differences between the diabetes mellitus type 1 and type 2 groups, suggesting that the type of diabetes must be taken into account when comparing the sensitivity of nerve conduction tests. In diabetes mellitus type 1, the sural/radial ratio had the clearest correlation with course of illness and was the first parameter to show a significant reduction. We conclude that the simple ratio between sural and radial amplitudes is a very sensitive parameter and abnormalities in this ratio provide the means for earliest detection of neuropathy in diabetes mellitus type 1.     

Chick gonadogenesis following early surgical bursectomy

Left ovaries of bursectomized chick embryos were examined on the 17th day of incubation in comparison to normal and sham-operated controls, by histological and histochemical observations. The results show that in bursectomized embryos the cortex appears irregulary developed, with a significant decrease in the mean thickness and in the percentage of the secondary sex cords in the total cortical area. Furthermore, the germinal epithelium appears thicker and the subcortical medulla and the tunica albuginea more compact. The greater activity of the enzyme ⁵–3-hydroxysteroid dehydrogenase ( ⁵3HSD) found in ovaries of bursectomized embryos (histochemical method) could be related to an endocrine dismetabolism affecting the cortical development. On the basis of these results and those of other authors, some hypotheses are advanced. In particular, an action of the bursal factor on GTH receptors could be the factor responsible of the enhanced steroidogenic activity altering the hormonal environment.     

Image perception and interpretation in senology. The relationship between the clinical picture, radiological sign and histology]

Once more, the authors are confronted with the difficult interpretation of senological images. When reviewing the radiologic features of a series including the symptomatic, the asymptomatic and the male breasts, the goal is to relate the patterns to clinical and histologic findings in order to improve the perception of the radiologist himself in transferring and integrating the information. The final conclusions, after reviewing the images, are: a) for the correct interpretation of senological images, the sign must be correlated with clinical findings and with data from other modalities; b) the radiologist's attitude must be always investigative and never exhaustive, due to the variability of all factors, which sometimes make a judgement of "radiological tranquility" in the breast impossible; c) the radiologist must, nowadays, improve his perception of senological images, thus becoming the one who knows how to correlate clinics to the images. By increasing his perception, his interpretation capabilities will certainly increase too.     

Different biological properties of paired HIV-1 isolates from peripheral blood mononuclear cells and cerebrospinal fluid.

Seven paired HIV-1 isolates from peripheral blood mononuclear cells (PMCs) and cerebrospinal fluid (CSF) of infected subjects at various stages of the disease were studied for their capacity to replicate in continuous cell lines (Molt-3 and U-937 cells) and to induce cytopathic effects "in vitro". Obtained results indicate that paired HIV-1 isolates from PMCs and CSF of the same patient can differ in their replicative activity "in vitro", suggesting that, at least in some cases, CSF isolates may represent a distinct subtype of HIV-1.     

Cyclooxygenase-2 activation mediates the proangiogenic effect of nitric oxide in colorectal cancer.

PURPOSE: Up-regulation of both inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) enzymes has been reported in colorectal cancer. We aimed at evaluating the possible interaction between the nitric oxide and COX-2 pathways, and its effect on promoting tumor angiogenesis. EXPERIMENTAL DESIGN: Expression of iNOS, COX-2, vascular endothelial growth factor (VEGF), and CD31 was analyzed in tumor samples and corresponding normal mucosa obtained from 46 surgical specimens. We also evaluated iNOS activity, prostaglandin E(2) (PGE(2)), cyclic GMP and cyclic AMP production in the same specimens. Nitrite/nitrate levels, and PGE(2) and VEGF production were assessed in HCT116 and HT29 colon cancer cell lines after induction and selective inhibition of the two enzyme pathways. RESULTS: A significant correlation was found between iNOS and COX-2 immunohistochemical expression. PGE(2) production significantly correlated with iNOS activity and cGMP levels. A significant correlation was also found among PGE(2) production, microvessel density, and VEGF expression. Coinduction of both iNOS and COX-2 activities occurred after lipopolysaccharide (LPS) and epidermal growth factor (EGF) treatment in HCT116 and HT29 cells. Inhibition of iNOS by 1400W significantly reduced both LPS- and EGF-induced PGE(2) production. Treatment with LPS, EGF, and arachidonic acid significantly increased VEGF production in the iNOS-negative/COX-2-positive HT29 cells. This effect was completely reversed by treatment with the selective COX-2 inhibitor celecoxib. CONCLUSIONS: Our data showed a prominent role of nitric oxide in stimulating COX-2 activity in colorectal cancer. This interaction is likely to produce a cooperative effect in promoting angiogenesis through PGE(2)-mediated increase in VEGF production.     

Synergistic cytotoxicity and pharmacogenetics of gemcitabine and pemetrexed combination in pancreatic cancer cell lines.

PURPOSE: Gemcitabine is an inhibitor of ribonucleotide reductase (RR) and DNA synthesis and is an effective agent in the treatment of pancreas cancer. The present study investigates whether the multitargeted antifolate pemetrexed would be synergistic with gemcitabine against MIA PaCa-2, PANC-1, and Capan-1 pancreatic cancer cell lines. EXPERIMENTAL DESIGN: Cells were treated with gemcitabine and pemetrexed, and the type of drug interaction was assessed using the combination index. Cytotoxicity of gemcitabine was examined with inhibitors of (a) deoxycytidine kinase (dCK), which activates gemcitabine by phosphorylation, and (b) 5'-nucleotidase (drug dephosphorylation) and cytidine deaminase (drug deamination), the main inactivating enzymes. The effects of gemcitabine and pemetrexed on cell cycle were analyzed by flow cytometry, and apoptosis was examined by fluorescence microscopy. Finally, quantitative, real-time PCR was used to study the pharmacogenetics of the drug combination. RESULTS: Synergistic cytotoxicity and enhancement of apoptosis was demonstrated, mostly with the sequence pemetrexed-->gemcitabine. Pemetrexed increased cells in S phase, the most sensitive to gemcitabine, and a positive correlation was found between the expression ratio of dCK:RR and gemcitabine sensitivity. Indeed, pemetrexed significantly enhanced dCK gene expression (+227.9, +86.0, and +135.5% in MIA PaCa-2, PANC-1, and Capan-1 cells, respectively), and the crucial role of this enzyme was confirmed by impairment of gemcitabine cytotoxicity after dCK saturation with 2'-deoxycytidine. CONCLUSIONS: These data demonstrate that the gemcitabine and pemetrexed combination displays schedule-dependent synergistic cytotoxic activity, favorably modulates cell cycle, induces apoptosis, and enhances dCK expression in pancreatic cancer cells.     

Fenretinide breast cancer prevention trial: drug and retinol plasma levels in relation to age and disease outcome.

OBJECTIVES: To assess, in women participating in a breast cancer prevention trialon fenretinide (4-HPR), the relationship of drug and retinol levels with the risk of second breast malignancy, taking into account age and menopausal status. METHODS: In a multicenter prevention trial, women with early breast cancer were randomly assigned to receive no treatment or 200 mg of 4-HPR/day for 5 years. Blood was collected at baseline and on a yearly basis during intervention from women recruited at the Istituto Tumori (Milan, Italy; 818 and 756 in the 4-HPR and control arm, respectively, who accounted for 53% of the participants in the trial). The plasma concentrations of 4-HPR, its main metabolite N-(4-methoxyphenyl) retinamide, and retinol were assayed by high-performance liquid chromatography. Three age ranges (or=56 years), menopausal status at baseline, and disease outcome at a median follow-up of 97 months were taken into account in the analysis. RESULTS: Baseline retinol levels were significantly lower (P or=46 years versus or= 0.71; P 相似文献