Solid papillary breast carcinoma with mucinous differentiation

A case is reported of a solid variant of infiltrating papillary carcinoma of the breast with mucinous differentiation in a 74-year-old woman. Macroscopically, the tumor was solid and lobular, 4.5 cm in diameter. Light microscopy showed solid papillary invasive carcinoma mixed with infiltrating ductal carcinoma, not otherwise specified. Abundant intracellular and extracellular acid mucin produced by the solid papillary tumor cells was proven histochemically by: PAS, PAS-D, mucicarmine and alcian blue. Immunohistochemically, the papillary carcinoma cells were strongly reactive to estrogen receptors, and weakly to moderately reactive to smooth muscle actin. We suggest that papillary carcinoma of the breast could have potentially high degree of aggressiveness, and that differential diagnosis of these rare tumors might be a histopathological problem.     

Bladder tumors in young people

Tumors of the bladder, particularly urothelial carcinoma (UC) are very rare malignant diseases in young people. They mostly occur in elder persons of male gender. We present 8 patients below 35 years of age, (average age 24.7), in whom the presence of UC was verified. The main symptom was total or terminal hematuria. The results showed that 5 patients had low-risc group of tumors (G1, pTa), while 3 tumors were of medium-risk group (G2, pT1). We concluded that UC in young people was low-grade and non-invasive. However, for better evaluation it was necessary to observe patients for longer period of time.     

Experimental photodynamic therapy with MESO-tetrakisphenylporphyrin (TPP) in liposomes leads to disintegration of human amelanotic melanoma implanted to nude mice

Liposomal meso-tetrakis-phenylporphyrin (TPP) was tested for photodynamic therapy (PDT) of human amelanotic melanomas implanted in nude mice. After intratumoural TPP application (15 mg x kg(-1)) followed by PDT lamp irradiation (600-700 nm, 635 nm peak), tumours retained their original volume up to the 23rd day post-PDT, whereas volumes increased 6 times in controls. PDT with intravenously (i.v.) administered liposomal (3.2 mg x kg(-1)) TPP mostly disintegrated tumours to zero volumes. Melanoma remissions were accompanied by tumour surface necroses and were documented by the appearance of nontumourous cells with nonpycnotic nuclei. Spatial arrangement of capillaries in remissing tumour was the same as in healthy surrounding tissue. Lower TPP doses (1, 0.3 and 0.1 mg x kg(-1)) were more or equally efficient than hydrophilic TPPS(4) (3.2 mg x kg(-1), i.e., sulfonated TPP), i.v. administered also in liposomes. Liposomal TPPS(4) only delayed the onset of subsequent tumour growth. Commercial Photosan 3 disintegrated tumours only in doses of approx. 7.5 mg x kg(-1); in lower doses it was less efficient than TPPS(4). The second PDT cycle (3.2 mg x kg(-1) TPP or 7.5 mg x kg(-1) Photosan 3), performed in a few unsuccessfully cured mice, predominantly led again to tumour remissions. Since the measured TPP and TPPS(4) content in melanomas was similar, these results demonstrate the advantage of PDT with a hydrophobic photosensitizer such as TPP. Photophysical properties of TPP and TPPS(4) are equal, but TPP has probably more favorable intracellular distribution, as documented by our studies, which leads to more efficient PDT. Consequently, liposomal TPP is suggested as a potentially suitable efficient preparation for PDT.     

Objective assessment of the degree of dementia by means of EEG

The aim of the study was to elaborate a method to estimate the degree of cognitive impairment in Alzheimer's disease from the EEG quantitative indicators. We examined 38 unmedicated patients with a diagnosis of Alzheimer's disease, with various stages (mild, moderate, and severe) of dementia. The EEG recordings were evaluated both visually and by means of computer analysis. The EEG spectra and coherences in 6 frequency bands were calculated in 16 EEG derivations. Among various EEG indicators, a decrease in the alpha coherence and an increase in the delta coherence was found to be most significantly correlated to the degree of dementia. Combining 6 variables from the spectrum and coherence analysis by means of the multiple regression model, a high correlation (r = 0.87) between a set of EEG variables and the Mini-Mental State Examination score could be obtained. The results suggest that the EEG can supplement the clinical examination by providing an independent assessment of the degree of dementia. The results also suggest that the EEG coherences are of particular interest in dementia, being an indicator of the signal transfer between various parts of the brain cortex.     

Effect of elevated K(+), hypotonic stress, and cortical spreading depression on astrocyte swelling in GFAP-deficient mice

Glial fibrillary acidic protein (GFAP) is the main component of intermediate filaments in astrocytes. To assess its function in astrocyte swelling, we compared astrocyte membrane properties and swelling in spinal cord slices of 8- to 10-day-old wild-type control (GFAP(+/+)) and GFAP-knockout (GFAP(-/-)) mice. Membrane currents and K(+) accumulation around astrocytes after a depolarizing pulse were studied using the whole-cell patch-clamp technique. In vivo cell swelling was studied in the cortex during spreading depression (SD) in 3 to 6-month-old animals. Swelling-induced changes of the extracellular space (ECS) diffusion parameters, i.e., volume fraction alpha and tortuosity lambda, were studied by the real-time iontophoretic tetramethylammonium (TMA(+)) method using TMA(+)-selective microelectrodes. Morphological analysis using confocal microscopy and quantification of xy intensity profiles in a confocal plane revealed a lower density of processes in GFAP(-/-) astrocytes than in GFAP(+/+) astrocytes. K(+) accumulation evoked by membrane depolarization was lower in the vicinity of GFAP(-/-) astrocytes than GFAP(+/+) astrocytes, suggesting the presence of a larger ECS around GFAP(-/-) astrocytes. Astrocyte swelling evoked by application of 50 mM K(+) or by hypotonic solution (HS) produced a larger increase in [K(+)](e) around GFAP(+/+) astrocytes than around GFAP(-/-) astrocytes. No differences in alpha and lambda in the spinal cord or cortex of GFAP(+/+) and GFAP(-/-) mice were found; however, the application of either 50 mM K(+) or HS in spinal cord, or SD in cortex, evoked a large decrease in alpha and an increase in lambda in GFAP(+/+) mice only. Slower swelling in GFAP(-/-) astrocytes indicates that GFAP and intermediate filaments play an important role in cell swelling during pathological states.     

Genotype phenotype correlation in a pediatric population with antithrombin deficiency

Inherited antithrombin (AT) deficiency is a rare autosomal dominant disorder, caused by mutations in the AT gene (SERPINC1). Considering that the genotype phenotype relationship in AT deficiency patients remains unclear, especially in pediatric patients, the aim of our study was to evaluate genotype phenotype correlation in a Serbian pediatric population. A retrospective cohort study included 19 children younger than 18 years, from 15 Serbian families, with newly diagnosed AT deficiency. In 21% of the recruited families, mutations affecting exon 4, 5, and 6 of the SERPINC1 gene that causes type I AT deficiency were detected. In the remaining families, the mutation in exon 2 causing type II HBS (AT Budapest 3) was found. Thrombosis events were observed in 1 (33%) of those with type I, 11 (85%) of those with AT Budapest 3 in the homozygous respectively, and 1(33%) in the heterozygous form. Recurrent thrombosis was observed only in AT Budapest 3 in the homozygous form, in 27% during initial treatment of the first thrombotic event. Abdominal venous thrombosis and arterial ischemic stroke, observed in almost half of the children from the group with AT Budapest 3 in the homozygous form, were unprovoked in all cases.

Conclusion: Type II HBS (AT Budapest 3) in the homozygous form is a strong risk factor for arterial and venous thrombosis in pediatric patients.