[The use of an immunohistochemical method for detecting N7-methylguanine in human cells].

An immunohistochemical method, followed by silvering (Ag-treatment) of the final product of peroxidase reaction for N7-methylguanine detection, was first employed for human cells treated in vitro with N-methylnitrosourea. This method appeared to be highly specific and sensitive, compared to the routine immunohistochemical technique. Evidence has been provided on the application of Ag-treatment for detecting N7-methylguanine in the esophagus epithelium of patients with a high risk of cancer with this particular locality.


[Increasing the sensitivity of an immunohistochemical method for detecting carcinogen adducts with DNA].

Application of polyclonal antibodies against N7-methylguanine (N7-MG) for immunohistochemical detection of the DNA damage following exposure to methylnitrosourea in cultured cells (CHO and IAR-27) has been shown. The approaches were applied: a) an extraction of nuclei, and b) a silver intensification of the end product of peroxidase reaction. Both the approaches were effective in increasing the sensitivity of immunohistochemical detection of N7-MG, the latter technique being most sensitive. It is proposed that the silver intensification technique is very perspective to have a high levels of sensitivity and specificity, a sufficient contrast and preservation of the cell morphology. The efficiency of the new approach in application to the purposes of molecular epidemiology is discussed.


[The mitotic cycle and DNA repair in UV-irradiated murine neuroblastoma cells].

A correlation has been shown between a reduced rate of movement of UV-irradiated neuroblastoma cells from G1 into S phase, an essential increase of cells in S phase while progressing through the cell cycle, and a defect in free DNA synthesis on a damaged template. These indices may reflect one and the same cell response to the UV light.


[The effect of 3-aminobenzamide on the mitotic cycle of Chinese hamster cells cultured on a medium with 5-bromodeoxyuridine following ionizing radiation action].

A specific inhibitor of poly(ADP-ribose)polymerase-3-aminobenzamide (6 mM) has been shown to: 1) reduce survival of non-irradiated CHO-K1 cells, cultivated in medium containing 5-bromodeoxyuridine (10 mkM, BDU cells), and increase their radiosensitivity; 2) induce G2 delay in BDU cells while progressing through the cell cycle as analysed by the DNA flow cytometry; 3) increase to a great degree G2 delay in X-irradiated BDU cells. 3-Aminobenzamide is primarily effective when it is present during the first or two first cell cycles after the initial addition of BDU. The above data confirm the involvement, presumably an indirect one, of ADP-ribosylation in the DNA repair through affecting the chromatin structure.


[The effect of Mycoplasma contamination on the karyotypic structure of a skin fibroblast cell line from the Indian muntjac].

The karyotypic variability has been studied in a low chromosomal cell line of the Indian muntjak skin fibroblasts contaminated with Mycoplasma arginini R-16 and Acholeplasma laidlawii A. The mycoplasmal contamination exerted influence on the cell distribution for the chromosome number. The frequency of the modal class cells with 7 chromosomes, having the main structure variant of the karyotype (MSVK) 2 + 2 + 1 + 1 + 1, was seen to decrease, while the frequency of the submodal class cells with 6 chromosomes, having MSVK 2 + 2 + 1 + 1 because of the loss of Y1 chromosome from MSVK 2 + 2 + 1 + 1, to increase. The frequency of chromosomal aberrations, predominantly that of dicentrics, was higher in the contaminated variants. Dicentrics were mainly produced by chromosomes 1 and 2. They were formed by a nonrandom combination of chromosomes and their arms. Possible correlations are discussed between aneuploidy and dicentric chromosome formation in low chromosomal cell lines, and cell adaptations to culture conditions.


[The cellular mechanism for the formation of lamellar bodies in type-II pneumocytes in rat lungs].

Pneumocyte type II cells from lungs of native rats and of rats that inspired a hypoxic mixture of gases were investigated by transmission electron microscopy. In cells of experimental rats, membrane structures were found that well compare with lamellar bodies. Experimental results and analysis of literature allowed to put forward a hypothesis about the cell mechanism of formation of lamellar bodies from the spiral twisted membranes of the endoplasmic reticulum.


Plasma steroid transport in subjects with tumors of hormonal target organs: a review.

Tumors derived from a hormonal target organ are assumed to be stimulated by the same hormone that stimulates the normal target tissue. In spite of attempts to acquire direct indications of a correlation between hormones and cancer, none have been definitive because studies of total and free hormone levels have given contradictory results. For this reason, attention has shifted to the study of plasma binding and transport of hormones, that is, of the proteins responsible for modulation of the hormone effect and thus of hormone bioavailability. The data reviewed indicate that in-depth study of the transport and binding system of sex steroids would give new information about the endocrine characteristics of cancer patients.


The effects of the macrocyclic lactone bryostatin-1 on leukemic cells in vitro.

The macrocyclic lactone bryostatin-1 was found to exert in vitro antineoplastic activity against several leukemic cell lines, including human K562 erythroleukemia, HL60 promyelocytic leukemia, REH and MOLT-4 lymphoblastic leukemias, CCRF-CEM lymphoma, KG-1 myeloid leukemia, and murine P388 lymphocytic leukemia. No statistically significant difference in sensitivity to bryostatin-1 was found between adriamycin-resistant P388 and K526 subclones and their sensitive counterparts. Freshly explanted clonogenic leukemic cells showed a variable sensitivity to bryostatin-1 in 10/12 tested samples. The IC50 of clonogenic leukemic cells was 4 x 10(-3) M bryostatin-1, and that of normal marrow CFU-GM was 10(-5) M. Leukemic cells exposed to bryostatin-1 showed a variable degree of monocytic differentiation as evaluated by ANAE staining and morphology. Bryostatin-1 is also able to inhibit the growth of CFU-GM from myelodysplastic marrow and to shorten the duration of dysplastic hematopoiesis in liquid culture. In conclusion, these data suggest that bryostatin-1 is a potent antileukemic agent in vitro that may be potentially useful for clinical studies.


Effect of medroxyprogesterone acetate on immunohistochemical expression of estradiol in endometrial carcinoma.

The effect of medroxyprogesterone acetate (MPA) on the immunohistochemical expression of estradiol (E2) was investigated in 25 cases of endometrial carcinoma. Twenty-three cases of the endometrial carcinomas showed positive immunoreactivity for E2. The immunohistochemical expression of E2 was more intensive in carcinoma cells than in stromal cells. Although the morphologic alterations induced by MPA treatment were observed only in 2 cases who were administered more than 30,000 mg of MPA, the staining intensity in most cases appeared to decrease after the treatment. The decrease in E2 immunoreactivities of cancer cells as well as of stromal cells in Grade 1 or Grade 2 was significant. These results suggest that MPA might decrease the E2 content in endometrial carcinoma cells as well as in stromal cells.


Bone marrow histopathology and prognosis in malignant lymphomas.

Bone marrow trephine biopsies of patients with non-Hodgkin's malignant lymphomas (ML), followed for at least 4 years, were investigated using univariate and multivariate survival analyses to detect which anagraphic data and histomorphologic medullary patterns before therapy were related to the prognosis. In 234 ML (146 low grade, 88 high grade), univariate analysis showed that survival was reduced by bone marrow involvement, absence of reactive lymphoid nodules, and low marrow cellularity. Moreover, in low-grade ML, patients 50 years or older and showing absence of myeloid hyperplasia, excess of hemosiderin and mast cell hyperplasia had significantly lower-survival rates. The prognostic relevance of these parameters did not change when cases without marrow involvement were separately analyzed. Multivariate analysis showed that, besides marrow involvement, age and myeloid hyperplasia had significant prognostic importance in low-grade ML, and lymphoid nodules in high-grade ML. Our data confirm the value of bone marrow histopathology in ML and indicate that the prognosis is related not only to medullary involvement but also to the morphology of the uninvolved marrow.


Histology as a prognostic factor in early gastric cancer.

Of 431 patients with gastric cancer observed in our institution, 23 (5.3%) had early gastric cancer (EGC). Macroscopic presentation, histology, depth of invasion, and lymph node involvement were evaluated in all the cases. All patients underwent surgery and an intensive follow-up was performed. Five of the 23 patients progressed, and the risk factors were examined. Histology seemed to be the main prognostic factor in our study, since intestinal type of EGC was associated to a significantly better prognosis. Total gastrectomy is indicated in the proximal localization of EGC, and should perhaps be performed also in cases presenting undifferentiated histology.


Minimally differentiated acute myeloid leukemia: a morphologic, cytochemical and ultrastructural study.

Seven of 368 cases of acute myeloid leukemia (AML) could not be subclassified by routine morphologic, cytochemical and immunologic analyses during the period January 1989 to December 1990. Further investigations including ultrastructural examination, anti-myeloperoxidase and myeloid specific antigen analysis were carried out in all these patients and they were classified as AML-MO, as per the FAB criteria. Morphologically these blasts resembled ALL-L2/AML-M1. Cytochemically they were negative for Sudan black, myeloperoxidase, periodic acid-Schiff, and non-specific esterase. On initial immunophenotypic analysis, they could not be classified into B, T or myeloid lineages. Further investigations revealed CD13 and CD33 positivity in 4 of 6 patients. Anti-myeloperoxidase was positive in 6 of 6 patients and ultrastructural examination revealed myeloperoxidase-positive blasts in 6 of 7 cases. Cytogenetic analysis done in one patient revealed 60% abnormal metaphases. Six of 7 cases were treated with aggressive chemotherapy. One patient achieved complete remission but relapsed after 6 months, whereas others were resistant to treatment. Hence we conclude that an aggressive investigative and therapeutic approach is required to identify and treat AML-MO.


Ultrastructural modifications in one case of hairy cell leukemia during alpha-interferon therapy.

There are many reports concerning the morphology of hairy cell leukemia (HCL), but, to our knowledge, there are no data on the ultrastructural modifications of HCL during interferon therapy. The ultrastructural modifications of neoplastic cells in peripheral blood in a case of HCL were investigated before and 2 and 4 months after beginning treatment with human lymphoblastoid alpha-interferon. Before therapy, hairy cells displayed the typical cytoplasmic projections, and 4% contained ribosome-lamellae complexes (RLC) (the cells contained up to 7 RLC). Two months from the beginning of therapy, hairy cells had shorter projections, RLC had disappeared, and tubuloreticular structures (TRS) had appeared in 2.2% of the elements. Four months from the beginning of therapy, TRS persisted in 2.3% of hairy cells, cylindrical confronting cisternae (CCC) appeared in 6.8% of the cells, and uncommon RLC, in close contact with the rough endoplasmic reticulum and nuclear membrane, were found in 1.5% of the elements. The cells contained up to 3 RLC. Our data confirm that interferon stimulates the synthesis of TRS and CCC, whereas the reappearance of uncommon forms of RLC could reflect their neosynthesis, possibly related to the interferon therapy. The frequent findings of a close contact between RLC and nuclear membrane support the view that RLC are derived not only from rough endoplasmic reticulum, but also from the nuclear membrane.


Cationic content in multiple mammary cysts.

One hundred and ninety-six breast cyst fluid samples from 78 consecutive patients with multiple cysts were subdivided according to the K+/Na+ ratio: type 1 (K+/Na+ ratio > 1) and type 2 (K+/Na+ ratio < or = 1). Cysts of the same type were found in 57.7% of patients (concordant group). Such a finding suggests that in patients bearing multiple cysts, all aspirated fluids need to be classified on the basis of their cationic composition. In the concordant group, type 1 cysts were more frequent than in the discordant group (80.3% vs 59.5%, P = 0.002). High K+/Na+ ratios (> 4.0) were present in 64% of type 1 cysts in the concordant group compared to 37.7% in the discordant group (P = 0.001), which suggests a different activity of the epithelium lining the cyst wall.


Osteosarcoma of the extremity metastatic at presentation: results achieved in 26 patients treated with combined therapy (primary chemotherapy followed by simultaneous resection of the primary and metastatic lesions).

From September 1986 to December 1989, 26 selected patients with high-grade osteosarcoma of the extremities metastatic at presentation were treated with primary chemotherapy (high doses of methotrexate, -cisplatinum and adriamycin) followed by surgery. Twenty-one cases underwent resections of the primary and metastatic tumor at the same time; owing to the disappearance of lung metastases after preoperative chemotherapy in 3 cases, only the primary tumor was operated on. Due to progression of the disease in 2 patients, no surgery was performed. Histologic examination of the resected specimen was performed to evaluate the percentage of necrosis produced by chemotherapy on the primary and metastatic tumor. After surgery, the patients received further chemotherapy with the same drugs used preoperatively plus ifosfamide and VP-16. The histologic response of the primary tumor was good (> 90% tumor necrosis) in 25% of the cases; in the resected metastatic nodules, 23% had good responses. A discrepancy between the histologic response of the primary and secondary tumor was observed in only 15% of the cases. These results seem to confirm the validity of the strategy (widely used today in the neoadjuvant treatment of non-metastatic osteosarcoma) of changing the postoperative treatment when the histologic response of the primary tumor is poor. At an average follow-up of 3.5 years, only 6 patients remained disease-free; 19 patients relapsed and 1 patient died for adriamycin cardiotoxicity. Of the 19 relapsed patients, 16 died and 3 are still alive but with uncontrolled disease. These results are much worse than those obtained in 144 cases of non-metastatic osteosarcoma of the extremities treated in the same period with the same preoperative chemotherapy (77% with good response in the primary tumor and 78% with continuous disease-free survival). The data suggest that a very effective neoadjuvant chemotherapy for nonmetastatic osteosarcoma of the extremities gives disappointing results in osteosarcoma of the extremities which is metastatic at presentation.


Case report: a patient with Hodgkin's disease after treatment for testicular cancer.

A young patient developed Hodgkin's disease 11 years after surgical, chemotherapeutic and radiation treatment for stage IIIA embryonal carcinoma of the testis. The importance is stressed of establishing a tissue diagnosis when there is an unexpected course of the disease.


Colonic metastasis of a renal carcinoma. A case report.

A 64 year-old man with a metastatic clear-cell renal carcinoma experienced low intestinal bleeding. The endoscopy revealed a polypoid mass in the left colon which proved to be a metastasis of the renal carcinoma. This is an uncommon cause of intestinal hemorrhage, and a rare localization of metastatic deposits.


Neuroblastoma presenting as protein-losing enteropathy.

Protein-losing enteropathy is often reported to be associated with malignancies such as Hodgkin's disease, non-Hodgkin's lymphoma, and mesenteric mesenchymoma, but it seldom complicates neuroblastoma. In this report, we describe a case of neuroblastoma presenting as protein-losing enteropathy in which neurohumoral mechanisms were involved.


A case of Waardenburg syndrome and aganglionosis.

Waardenburg's syndrome is characterized by a broad nasal root, pigmentation disturbance and congenital deafness while aganglionosis is described as the partial or complete lack of ganglion cells in the alimentary tract. This report describes a five-day-old male infant with Waardenburg's syndrome associated with total aganglionosis of the colon, ileum and distal jejunum and draws attention to the causal relationship between these two entities.


Kawasaki syndrome.

Kawasaki syndrome, also known as mucocutaneous lymph node syndrome, is an acute vasculitis of infants and young children. We describe a four-year-old girl who presented with fever, a diffuse erythematous maculopapular rash, bilateral nonpurulent bulbar conjunctivitis, dry, red, fissured lips, a tongue with a strawberry "appearance", an erythematous pharynx, indurative erythema, and edema and desquamation of the face, hands and feet. She probably developed mitral valve prolapse during the course of the disease. The diagnosis of Kawasaki syndrome was arrived at by excluding other diseases and by the presence of all the clinical criteria for Kawasaki syndrome. Since this syndrome is rarely encountered in Turkey, this case is presented and the literature regarding the syndrome is reviewed.


Evaluation of growth hormone secretion and insulin-like growth factor-1 in prepubertal children with thalassemia.

Growth retardation is a clinical feature of patients with thalassemia major, and endocrine studies have frequently revealed the presence of normal growth hormone (GH) secretion. The present study was undertaken in 14 prepubertal thalassemic children (9 males and 5 females), aged 2(2/12) to 10(3/12) years, with the aim of evaluating GH response to i.v. arginine, oral L-dopa stimulation and insulin-like growth factor-1 (IGF-1) levels. Eleven patients had peak serum GH levels less than 7 ng/ml and two patients had peak serum GH levels of 7-10 ng/ml with arginine. Similarly, 10 patients had peak levels less than 7 ng/ml and one patient had a peak level of 7-10 ng/ml with L-dopa. Thus, nine of the patients had GH deficiency and two had partial GH deficiency. Three patients had elevated basal GH values. The serum IGF-1 levels in the patients were not statistically different from the levels in the controls, but three patients had low IGF-1 values. These findings suggest a defect in the regulatory mechanisms of GH secretion.


The effect of nifedipine on secretory diarrhea in mice.

The aim of this study was to determine whether castor oil-induced secretory diarrhea in mice could be ameliorated by nifedipine, a calcium channel blocking agent in mice. Ten animals received nifedipine in a dose of 1 mg/30 g/body weight and another ten animals received only distilled water via an orogastric feeding tube. Fifteen minutes after the administration of the drug or the distilled water, castor oil was given to all animals. The mean body weight loss was found to be higher in the control group than in the nifedipine treated group two hours after the administration of castor oil. These findings indicate that nifedipine may have a therapeutic role in castor oil-induced secretory diarrhea.


The role of viruses and Mycoplasma pneumoniae in lower respiratory tract infections in childhood.

Acute lower respiratory tract infections are one of the major causes of childhood morbidity and mortality in developing countries. This study was undertaken at Hacettepe University Children's Hospital to determine the role of viruses and Mycoplasma pneumoniae in respiratory tract infections in children. Eighty-three patients with lower respiratory tract infections were selected at random from among the children admitted to the hospital for evaluation of respiratory symptoms. Acute and convalescent serum samples were collected from all patients for the complement-fixation test and the following antigens were used: respiratory syncytial virus (RSV), adenovirus, parainfluenza virus Type 1, influenza viruses A and B, and Mycoplasma pneumoniae. The test was positive in 39 of 83 patients (47%), and RSV was the most frequent agent detected serologically (15.7%).


Carrier detection by DNA analysis in Duchenne muscular dystrophy families.

We applied DNA analysis techniques to Turkish families whose members were afflicted with Duchenne/Becker muscular dystrophy. The aim of this study was to establish a prenatal diagnosis of this anomaly and to determine the carrier state. All of the techniques used in established diagnosis centers are now applied routinely in our laboratory. Both Southern analysis and polymerase chain reaction (PCR) methods were used for deletion detection in patients and restriction enzyme fragment length polymorphism (RFLP) determination for linkage analysis in women at risk. CA repeated sequence length polymorphism, the most recent technique for linkage analysis, was also applied. About 250 individuals from seventy-nine families were investigated and thirty-six entire families were screened. Twenty-five women were found to be carriers while thirty seven were non-carriers. The carrier state could not be determined in three women.


The value of CSF adenosine deaminase levels in the differential diagnosis of childhood meningitis.

In this study, adenosine deaminase (ADA) levels of serum and cerebrospinal fluid (CSF) in a total 28 children (13 with bacterial meningitis, 5 with mumps meningoencephalitis and 10 with febrile convulsions) were determined. The comparisons between the serum values were insignificant (p greater than 0.05) but the CSF levels of the children with bacterial meningitis were higher than in the others (p less than 0.05). These findings suggest that serum ADA levels are not important in the diagnosis and differential diagnosis of these diseases. However, ADA levels of CSF may be useful in differentiating between bacterial and viral meningitis.


[Use of water-soluble 2-nitro-4-sulfophenyl ester of adipic acid for preparation of peptide protein conjugates].

Two synthetic peptides were conjugated with bovine serum albumin by means of 2-nitro-4-sulfophenyl ester of adipic acid. The amino acid analysis of the conjugates has shown that 14-15 molecules of the peptide are coupled per 1 molecule of the albumin during 10 min. The number of coupled molecules is the same when the reaction time increases to 24 hours. So, 2-nitro-4-sulfophenyl ester of adipic acid may be used parallel with the known bifunctional reagents to obtain peptide-protein conjugates.


The significance of early panendoscopy in caustic ingestion in children.

Fourteen cases of esophageal and gastric burns following the accidental ingestion of a caustic substance are presented. Early fiberoptic endoscopy was necessary, for it made possible a precise assessment of the severity and extent of injury and the application of proper conservative therapy. Signs and symptoms of caustic burns in children are an unreliable guide to injury, therefore, panendoscopy should be performed as soon as possible. A delay in the performance of a fiberoptic examination could result in the perforation of the affected organs.


[Effect of the degree of liposome oxidation on adsorption by montmorillonite].

The influence of the degree of liposomes oxidation on the parameters of their adsorption by montmorillonite was studied. It was shown that accumulation of the products of oxidation in liposomes, which occurred in the process of their incubation, feebly influenced the ability of liposomes to adsorb on the surface of the clay mineral. The increase of the degree of liposomes oxidation in this case lead to the lowering of the values of adsorption heats, however the kinetics of heat production was preserved.


[Hydrolysis of polymeric fibrin by plasmin, miniplasmin, microplasmin and trypsin].

125I-labeled polymeric fibrin hydrolyzed with plasmin, Val442-plasmin (miniplasmin, Lys530-plasmin (microplasmin) and trypsin has been studied for radioactivity of its separate electrophoretic bands. The reaction of hydrolysis was stopped at a moment of a two-fold decrease of the fibrin clot turbidity (t1/2) at the wave length 350 nm. For plasmin, miniplasmin, microplasmin and trypsin taken in the same caseinolytic activities t1/2 was 12.4, 40.0 164.1 and 76.8 min, respectively. Differences in composition of fibrin digests taken at t1/2, are demonstrated: the content of high-molecular components of digests decreases in the order of plasmin greater than miniplasmin greater than microplasmin greater than trypsin, thus showing differences in the processes of fibrin clot structure disruption by the enzymes.


[Status of the antioxidant protective system of rat liver exposed to carbon tetrachloride].

The dynamics of enzyme activity of antioxidative protective system of the liver and the content of restored glutathione have been studied in rats poisoned by CCl4 injection. During the first hours followed the injection against the background of maximum accumulation of dienic conjugates and decrease of the restored glutathione level no significant changes in the enzyme activity of the antioxidative protective liver system were observed. At the same time 48 hours later the superoxide dismutase and catalase activity decreased by 38% and 36%, respectively, with relative stability of glutathione-dependent enzymes and a two-fold increase of the restored glutathione level. It is shown that a fall of activity of the cytoplasmic antioxidative liver enzymes is not a result of the immediate inactivating effect of free-radical reactions initiated by CCl4, but is, evidently, caused by the covalent binding of its radical metabolites with corresponding macromolecules.


[Isolation of steroid-binding proteins on new affinity adsorbents].

Steroid-binding proteins of human blood are extracted and investigated on corticosteroid-hydrazide-oxypropyl-adsorbents by the affinity chromatography. The role of structural changes in the matrix-spacer-ligand system for different types of adsorbents is studied as well as a dependence of sorption on pH and salt environment. A dependence of the protein sorption on the isolated hydrazide groups is revealed. It is shown that hydrocortisone displays the highest binding activity to the protein pool in the affinity electroimmunoassay while the substance S-Reichstein and its 16-alpha-methyl analog--the least one.


[Biochemical bases of prevention of the cytotoxic effect of xenobiotics].

Possible sources of cytotoxicity of xenobiotics and main mechanisms of realization of their damaging effect are briefly considered. Protective system of a cell is characterized with regard for the peculiarities essential for development of principles of alimentary prophylaxis of cytotoxic effects of foreign compounds. Modern approaches to alimentary modification of the processes of biotransformation of xenobiotics and promotion of protective capacities of a cell are discussed.


[Structure and properties of the cell nucleus chromatin in the brain of rats exposed to gamma-radiation].

Exposure of rats to radiation in a dose of 1 Gy changes sensitivity of chromatin in the cerebral cortex cells to the action of DNAase 1, which promotes an increase of the DNA hydrolysis level and content of dissolved chromatin fractions. A day after irradiation the chromatin structure restores only partially and then (7-30 days after irradiation) it passes into a new, less compact state. The irradiation changes the chromatin ability to aggregation in the presence of Mg2+ and spermidine.


[Inhibition of yeast pyruvate decarboxylase by alkyl phosphates].

It is found that yeast pyruvate decarboxylase is inhibited by alkyl phosphates. Inhibition is competitive with respect to a substrate. The inhibition constants with n-butyl and n-heptyl esters of phosphoric acid are the values of the same order of magnitude. With an increase in the length of the alkyl phosphates hydrocarbon chain from 7 to 10 carbon atoms inhibition constants change drastically. For n-heptyl phosphate and n-decyl phosphate values KI are equal to 1.6 x 10(-4) M and 1.7 x 10(-6) M, respectively. A further increase in the number of carbon atoms in the alkyl substituent of phosphoric acid ester induces no reduction of the inhibition constant. Multiple-inhibitor experiments of pyruvate decarboxylase show that inorganic phosphate and n-decyl ester of phosphoric acid are mutually exclusive. It is suggested that the inhibition mechanism with alkyl phosphates includes the competition of the phosphoric acid residue with alpha-ketocarboxyl group of pyruvate as well as the interaction between a hydrocarbon radical and hydrophobic parts on the enzyme surface, one of them being outside the substrate binding site.


[Activity of glutathione-dependent enzymes and superoxide dismutase in peptic ulcer].

Activity of Cu, Zn-superoxide dismutase, glutathione-S-peroxidase, glutathione-S-transferase, glutathione reductase, glucoso-6-phosphate dehydrogenase and content of glutathione reduced in blood of patients with gastric and duodenal ulcer depending on the age and parallel lesion of the hepatobiliary system have been studied. Considerable inhibition of superoxide dismutase, glucoso-6-phosphate-dehydrogenase activity and decrease of the content of reduced glutathione, the most pronounced in patients with parallel lesion of the hepatobiliary system, have been revealed. Glutathione reductase activity is high in all the patients, except for aged and old people with parallel lesions of the liver and biliferous tracts. Glutathione peroxidase is essentially active in adult patients, especially in case of combined pathology. Glutathione peroxidase activity is lower in aged and old patients as compared to the age norm, while the level of glutathione-S-transferase activity is high; at the same time there are no considerable changes in the glutathione-S-transferase activity in adult patients. The mechanisms of compensation and decompensation of functioning of enzymatic antiradical and antioxidant system under the peptic ulcer depending on the age of patients and concomitant lesions of the hepatobiliary system are discussed.


[Redox processes in the retina and tunic tissues of the rat eye in experimental alkalosis].

It is shown in experiments is vivo that development of experimental metabolic alkalosis in rats is followed by changes in redox processes in the eye retina and tunic. For the first two months of the experiment the number of sulphydryl group decreases, while that of disulphide ones of water-soluble proteins and low-molecular compounds increases. The amount of oxidized metabolites of glycolysis and of a cycle of tricarboxylic acids (pyruvate, oxaloacetate, alpha-ketoglutarate) increases relative to the reduced ones (lactate, isocitrate, malate), as well as activities of hexokinase, pyruvate kinase, NAD-dependent malate dehydrogenase, while activities of fructose diphosphatase, glucoso-6-phosphate dehydrogenase, glutathione peroxidase and glutathione reductase fall. The content of malonic dialdehyde increases. 90 days later disorders of certain compensatory mechanisms of the metabolic system of alkalosis regulation probably occurred in the eye retina and tunic tissues: hexokinase and pyruvate kinase activity fell to the control values, while that of NAD-dependent malate dehydrogenase--below the control level; the content of lactate increased. Activity of glutathione-dependent enzymes remained low and the amount of malonic dialdehyde grew much more than in the previous terms.


[Changes in the intensity of DNA synthesis in immunocompetent mouse tissues by peptidoglycans of bacterial origin].

The data are presented on the effect of activation of by peptidoglycans from cell walls of Staphylococcus aureus and Brevibacterium flavum on the DNA synthesis intensity in the mice spleen, thymus and bone marrow in vivo. Maximum of the peptidoglycan influence on the DNA synthesis intensity is observed 12-36 hours after injection. As a rule, higher doses of the studied peptidoglycans (1 mg per one animal) activate the DNA synthesis more efficiently. Peptidoglycan from Br. flavum stimulates the DNA synthesis in all tissues more intensively then the peptidoglycan from S. aureus, which may be a result of its monomers' structure.


[Coenzyme-binding sites of the brain pyruvate dehydrogenase complex].

It is shown that the relative amount of the holoenzyme in the highly purified pyruvate dehydrogenase complex from the bovine brain is higher when the enzyme activity is assayed in the reaction of nonoxidative formation of acetaldehyde as compared to the pyruvate: NAD+ reductase reaction. The S0.5 values for thiamine pyrophosphate are as following: (TPP) (0.314 +/- 0.22) x 10(-7) M with reaction of nonoxidative formation of acetaldehyde, (0.188 +/- 0.08) x 10(-6) M and (1.65 +/- 1.16) x 10(-6) M in case of the pyruvate: NAD+ reductase reaction. TPP in the concentration of (0.5-6.0) x 10(-7) M completely protects the sites of nonoxidative formation of acetaldehyde from modification by the coenzyme analogs, 4'-oxythiamine pyrophosphate and tetrahydrothiamine pyrophosphate. However, the pyruvate: NAD+ reductase activity of the pyruvate dehydrogenase complex is inhibited in this case by 30-34%. The data obtained suggest that in contrast to the pyruvate: NAD+ reductase reaction the conversion of pyruvate to acetaldehyde occurs by the sites which tightly bound TPP.


[Ammonia metabolism in tissue of newborn animals in health and in digestive disorders].

Ammonium nitrogen was studied for its metabolism in the tissues of ruminants in transition from pre- to postnatal development in norm and with disorders in gastroenteric digestion. It is established that the intensity of ammonium genesis and glycolysis processes as well as a cycle of tricarbonic acids change in newborn calves as compared to adult animals. The ammonium toxicosis development in sick animals, which is confirmed by an increase of the ammonia level and intensification of the reactions of ammonium- and ureogenesis in tissues of the gastroenteric tract, liver and kidneys.


Alkyllysophospholipid influenced melanoma cell morphology is associated with decreased attachment to basement membrane.

The alkyllysophospholipid analog 1-0-octadecyl-2-0-methyl-3-phosphorylcholine (ET-18-OCH3) was examined for possible anti attachment effects on B16-F10 murine melanoma cells in vitro. At sub-lethal lipid concentrations B16-F10 cells were inhibited from attaching to reconstituted basement membrane (Matrigel) during a 45 min assay. This type of inhibition was also imparted by the isoprenoid farnesol but not by egg lysophosphatidylcholine (LPC) at concentrations up to 10 micrograms/ml. Both lipids were toxic to B16-F10 cells in the absence of bovine serum albumin (BSA), BSA (0.1%) completely protected the cells from lysis except when both lipids were combined as a mixture. Light and electron microscopy, as well as electronic sizing of cells, gave evidence of alkyllysophospholipid induced reduction in cell size which correlated well with attachment inhibition. The results suggest that alkyllysophospholipid induced reduction of cell surface area leads to inhibition of cell attachment to basement membrane which 8 with our experimental conditions, was not permanent since cells eventually attach within 24 h after treatment. The enhanced lytic effect the lysophospholipid imparts on the alkyl compound, in conjunction with the anti-attachment properties should be important areas for future research.


[Effect of ketoconazole on the activity of key enzymes of biosynthesis of cholesterol and its esters in the liver of rats maintained on a cholesterol-enriched diet].

Ketoconazole in vivo has been studied for its effect on the activity of key enzymes of the cholesterol and its esters' biosynthesis in the liver and on the cholesterol concentration in certain fractions of blood lipoproteins in normal and cholesterol-fed rats. It is established that ketoconazole decreases cholesterol concentration in low-density lipoproteins and in very low-density lipoproteins as well as decrease the acyl-CoA-cholesterol acyl-transferase activity and increases the 3-hydroxy-3-methyl-glutaryl-CoA-reductase activity in the liver microsomes of intact and test animals. It is supposed that the possible cause of the observed changes can be a disturbance in regulation of basic links of cholesterol metabolism in the liver.


[Effect of salvipholin on the carbohydrate and lipid metabolism in the rat liver in alloxan diabetes].

Peroral administration of salvipholin in a dose of 50 mg/kg to intact male rats (the body weight 180-220 g) had a positive effect on the carbohydrate-lipid metabolism in the liver and blood serum of animals. Administration of the same dose to rats with alloxan diabetes induced a significant decrease in the content of glucose, free fat acids, triglycerides and lysophospholipids of the liver and blood serum. The level of these components has sharply increased after subcutaneous alloxan administration in a dose of 150 mg/kg, the content of glycogen and pyruvic acid being normalized and insulin deficiency removed. These changes are closely related to salvipholin-promoted restoration of phospholipid spectra of the blood serum and liver of experimental animals disturbed under conditions of insulin deficiency. The possible mechanism of the salvipholin action is analyzed.


Comparative ultrastructure of needle aspiration biopsy and surgical resection specimens of lung tumors.

Ultrastructural examination affords conclusive evidence for classification of lung tumors. Tissue properly fixed for electron microscopy is not available in many cases, however. Ultrastructural diagnosis of resected specimens obviously follows, rather than directs, the surgical treatment. Fine-needle aspiration (FNA) of lung masses is recommended as a means to obtain lung tumor tissue for electron microscopy. Nevertheless, no comparison has been made between ultrastructural information gained from aspiration specimens and resected specimens. Electron microscopy was performed on transthoracic FNA specimens of 10 lung tumors for which surgical resection was subsequently performed. Glutaraldehyde-fixed specimens from FNA and surgical resection were prepared for electron microscopy according to routine procedures. Fixation of the FNA specimens was equivalent or superior to that of the resected specimens in 9 of the cases. Three of the FNA specimens contained necrotic as well as viable tissue. Features essential for diagnosis such as desmosomes, junctions, neurosecretory granules, intermediate filaments, glycogen, lipid, mucin, and microvilli were identifiable in both FNA and resected specimens. FNA specimens therefore yield a representative sample of the ultrastructural features of lung tumors when adequate cellular material is obtained. Use of a coaxial needle sampling technique with immediate microscopic assessment reduces the likelihood of retrieving only blood or necrotic tissue in the electron microscopy specimens.


[Cellular microbiosensors for methanol and ethanol determination on the basis of pH-sensitive field transistors].

Cellular sensors for methanol and ethanol determination were developed using immobilized mutant cells of methylotrophic yeasts Hansenula polymorpha and Pichia pinus (able to extrude protons in the presence of alcohol) and pH-sensitive field effect transistors (pH-SFETs). The intact cells of yeasts were immobilized in Ca-alginate gel to obtain a biomembrane. The minimal detectable response was obtained to approximately 0.5 mM of methanol and ethanol, a linear dependence of biosensor's response on the logarithmic alcohol concentration was observed in the range from 5 to 100 mM for both types of alcohol. The prospects for application of biosensors to determine alcohols in the analytical practice are discussed.


Limits of cryofixation as seen by Fourier transform infrared spectra of metmyoglobin azide and carbonyl hemoglobin in vitrified and freeze-concentrated aqueous solution.

The limits of cryofixation were probed by investigating metmyoglobin azide and carbonyl hemoglobin in approximately 5 wt% aqueous solution by Fourier transform infrared spectroscopy. Spectra of solutions cooled slowly and recorded in steps between 295 K and 190 K are compared with those obtained by "hyperquenching" either into their glassy states at 80 K, or into freeze-concentrated solution at 170 K. For metmyoglobin azide we conclude from an analysis of its covalently and ionically bound azide that it is impossible to freeze-in its high-spin/low-spin equilibrium even by hyperquenching, and that its vitrified state must correspond to a temperature T < 226 K for the Fe(II) site of the protein. In the amide I spectral region of carbonyl hemoglobin (HbCO), a band at approximately 1654 cm-1 due to alpha-helical structures is the dominant band in spectra recorded at ambient temperature and in the vitrified state, but in the spectrum of HbCO quenched at similar rates into a freeze-concentrated state, a band at approximately 1650 cm-1, tentatively assigned to unordered structures, becomes the dominant feature. This band is absent in the spectra of freeze-concentrated samples obtained by heating a vitrified sample to 170 K. We surmise that HbCO is dehydrated by freeze-concentration to a larger extent in solution quenched rapidly at 170 K than in a vitrified solution heated to 170 K, and that this dehydration is the primary cause for HbCO's perturbation. We conclude that freeze-concentration induced by heating a vitrified solution can cause less perturbations of a protein than does quenching into a freeze-concentrated state. Therefore it can be advantageous for the practice of freeze-etching to vitrify first a solution by "hyperquenching" and thereafter freeze-etch at e.g. approximately 170 K.


Acute myopathy associated with chronic licorice ingestion: reversible loss of myoadenylate deaminase activity.

A patient with acute rhabdomyolysis and absence of myoadenylate deaminase (MADA) associated with chronic licorice intoxication is presented. Clinical and laboratory examination of the patient and morphologic study over skeletal muscle were performed. The major effect of licorice intoxication is hypokalemia, which may explain most of the observed clinical symptoms and morphological changes. The absence of MADA may be a consequence of the direct toxic effect of licorice glycosides. To our knowledge, this is the first report in which a lack of MADA and chronic licorice intoxication has been shown to be associated with clinical, histochemical, biochemical, and morphological changes, which were completely reversed with potassium supplementation and licorice withdrawal.


[Blood lipids and characteristics of free radical processes in specific classes of lipoproteins in rats in the early periods after gamma-radiation].

The content of lipids and lipoproteins, the state of free-radical processes and the level of eicosanoids (prostaglandin F-1L and thromboxane B-2) have been studied in the blood plasma and in certain classes of lipoproteins in rats 2 and 24 h after external gamma-radiation in doses of 1.2 and 3 Gy. Hypertriglyceridemia and hyperprebetalipoproteinemia, whose expressivity increases with a radiation dose are revealed. The activation of free-radical processes, an increase of the thromboxane V-2 content and a decrease of the prostaglandin F-1L content are observed with a dose of 1 Gy.


Scanning tunneling microscopy of an ionic crystal: ferritin core.

Ferritin molecules were imaged directly in air by scanning tunneling microscopy (STM). The lateral dimensions were close to the values determined by electron microscopy, and the vertical dimension was much reduced. Several clusters of partially naked ferritin cores displayed a hexagonal structure of lattice constant 4.9 +/- 0.5 A. It is thus shown that the STM can be used to image thin ionic crystals at high resolution.


Chordomalike soft tissue sarcoma in the leg: a light and electron microscopic and immunohistochemical study.

A soft tissue tumor in the leg of a 67-year-old woman is described. This large tumor below the knee area infiltrated extensively the deep and superficial soft tissues but did not involve the bones. The tumor cells formed nodules resembling the architecture seen in chondroid tumors and chordoma. The tumor cells were often vacuolized, and there was extracellular myxoid matrix similar to that in chordoma or myxoid chondrosarcoma. Immunohistochemistry showed keratins 8 and 19, epithelial membrane antigen, and vimentin in most tumor cells, and there was also S-100 protein positivity in a number of tumor cells. Electron microscopy showed desmosomelike cell junctions and bundles of intermediate filaments resembling those seen in many epithelial neoplasms. Thus the tumor resembled chordoma in many respects. Because clinically no other primary tumor was found, this tumor is probably a chordomalike primary soft tissue sarcoma different from typical extraskeletal myxoid chondrosarcoma or chordoid sarcoma.


New STEM multisignal imaging modes, made accessible through the evaluation of detection efficiencies.

With its specific design for recording simultaneous signals, the scanning transmission electron microscope (STEM) offers unique imaging capabilities. In order to use them fruitfully, we have implemented, on a VG STEM equipped with a magnetic spectrometer, home-made detectors for recording multisignal images. This paper first describes a method developed for the quantitative evaluation of detection efficiency of all data-acquisition channels involved in these multisignal images. At this stage, new imaging modes become accessible, which can be classified following their specificity and sensitivity; scattering power image, elastic and inelastic images mean free path ratio images. Original applications encountered in the biological as well as in the materials science fields illustrate the possibilities of these various approaches, which can be of great interest in quantitative microscopy, analytical imaging or low-dose observation.


A method for observing cross-sectional views of biomembranes.

Cross-sectional views of intact biomembranes and synthetic lipid bilayer membranes were observed by electron cryomicroscopy using spontaneous orientation of disk-shaped membranes; purple membrane, thylakoid membrane, synthetic phospholipid membrane and a microcrystalline sheet made of Er-binding polypeptide were observed. The membranes were observed fully hydrated, embedded in vitreous ice, and their self-orientation was most probably caused by repulsion between their hydrophobic edges and their hydrophilic environment which forced their edges to be exposed to the air-water interface. The cross-sectional profiles of the native biomembranes were asymmetric and characteristic, whilst those of the synthetic membranes were symmetric and predictable by a simple model. Simple Fourier analysis showed that the cross-sectional images retained structural information up to a medium resolution.


Ciliary ultrastructure in primary ciliary dyskinesia and other chronic respiratory conditions: the relevance of microtubular abnormalities.

Twenty-eight subjects with chronic respiratory disease were investigated for clinical data, ciliary beat frequency of nasal mucosa (10 cases), and ciliary ultrastructure. The cases were divided into two groups: those considered compatible with primary ciliary dyskinesia (genetic), and those not fitting into this category (others). A case was defined as genetic if one or more of the following were present: dextrocardia, ciliary beat frequency less than 10 Hz, or an average dynein arm count (outer, inner, or both) of less than two per ciliary cross-section. In each of the genetic cases at least two of these parameters were present. The percentage of malformed microtubules was calculated from the total number of evaluated cross-sections for each case. Ciliary microtubular abnormalities of any kind were no more frequent in cases of primary ciliary dyskinesia than in other cases. The same was true for transposition and radial spoke defects.


Metastatic spindle cell malignant melanoma with prominent microvilli.

A metastatic spindle cell malignant melanoma with positive immunoreactivity for S-100 protein and HMB-45 antigen and the presence of premelanosomes is described in a lymph node of the neck 11 years after removal of a superficial spreading malignant melanoma from the arm. Ultrastructurally, long, slender microvilli created a pattern with great similarity to an anemone cell tumor. A more solid pattern without microvilli was also present. Despite the abundance of microvilli in the anemone part of the tumor, intracytoplasmic lumina were not observed. In addition, crystalline structures within enlarged mitochondria and intracisternal tubules were noted.


Ultrasonic analysis of edible fats and oils.

Low intensity ultrasound is a powerful analytical technique for investigating the physico-chemical properties of many biological and non-biological materials. In this article its application for the characterization of edible fats and oils is assessed. Ultrasound can be used to determine the dynamic rheology and composition of oils, the oil content and droplet size of emulsions and the solid fat content of partially crystalline emulsions. It is capable of rapid and precise measurements, is non-destructive and non-invasive, can be used on-line or off-line and is relatively inexpensive. Ultrasonic techniques will therefore prove a useful addition to the existing analytical techniques used to characterize fats and oils.


The effect of bone structure on ultrasonic attenuation and velocity.

The relationship between the structure of bovine cancellous bone, and its ultrasonic propagation parameters is investigated by means of a novel technique involving the application of large static loads, thereby changing the porosity in a controlled manner. The results show that for frequencies in the range 0.4 to 1 MHz, porosity decreases up to 35% are associated with a reduction in attenuation of up to 500%, whereas the velocity increases by roughly 35% for the same changes. The data taken overall suggest that in determining the ultrasonic attenuation coefficient at these frequencies, the amount of material in a given bone section is significantly less important than the distribution of that material.


Dependence of ultrasonic attenuation of liver on pathologic fat and fibrosis: examination with experimental fatty liver and liver fibrosis models.

To clarify the effect of the pathological state of the liver on ultrasonic attenuation, we produced two experimental rabbit models. The influence of fat on ultrasonic attenuation was examined using a fatty liver model without liver fibrosis, and that of fibrosis on attenuation using a liver fibrosis model without fatty infiltration. Ultrasonic data were obtained in vivo directly from the liver, and an acoustic attenuation coefficient slope was obtained by the spectral difference method. Tissue components of the liver, namely the total lipid, hydroxyproline and water contents, were measured precisely by quantitative methods. We revealed that ultrasonic attenuation depends mainly on fatty infiltration of the liver and to a lesser extent on fibrosis, but not on the water content.


Axial stress distributions between coaxial compressors in elastography: an analytical model.

We describe an analytical model to study the behavior of stress along the compression axis for different configurations of opposing circular compressors, as applied to elastography. The method is based on a hypothesis that the axial stress at any point on the axis is the superposition of the individual components of the stresses derived from the boundary conditions at either end. The determination of the axial stress behavior according to the model permits the correction of certain elastograms for depth-dependent stress. Experimental results have been presented to corroborate the model.


Fetal exposure from endovaginal ultrasound examinations in the first trimester.

Ultrasonic obstetrical examinations during the first trimester are now often performed endovaginally with higher-frequency (5-7.5 MHz) transducers operating closer to the fetus than for transabdominal examinations. To estimate exposure to the fetus, propagation distances were obtained from a retrospective study of 100 normal first-trimester endovaginal B-mode examinations. No significant dependence of attenuation on gestational age was observed. The range of the attenuation estimates was 1.8-10.4 dB. A mean attenuation of 5.0 dB at 5 MHz for an average depth of 2.8 cm resulted in an attenuation coefficient of .36 dB/cm/MHz. Exposure (ISPTA) to the fetus at each gestational week from three ultrasound units was very similar: worst-case values of the 100 cases ranged from 1.2-1.9 mW/cm2, well within the Food and Drug Administration (FDA) guidelines of 94 mW/cm2 for derated focused transducers. Energy density deposited to the anterior surface of the fetus during a typical examination, assuming that the transducer is kept stationary over one area for the entire period of the examination (which is unlikely), ranged from 143-217 mJoules/cm2, within the American Institute of Ultrasound in Medicine (AIUM) recommendations.


Human in situ dosimetry: differential insertion loss during passage through abdominal wall and myometrium.

We constructed a specialized in vivo exposimetry system and determined selected ultrasonic field quantities. We examined two groups of non-pregnant women (nulliparas = 14, multiparas = 9) under conditions of full and empty bladder. A calibrated 7-element linear array hydrophone was placed in the anterior fornix of the vagina in each subject. In the full bladder condition, the sound beam traversed the anterior abdominal wall and full bladder, whereas after voiding, the sound beam traversed the abdominal wall and anteverted uterine fundus. Each study was conducted using a 3.5 MHz mechanical sector transducer. Calibration data were recorded after completion of each in vivo experiment. Data from both groups were pooled for analysis. Assuming (1) the sound path through the full bladder is loss less, the insertion loss (ILFULL) should represent the insertion loss for the abdominal wall (ILABD WALL) 8.2 +/- 5.6 dB; whereas (2) for the empty bladder condition, (ILEMPTY) represents (ILABD WALL+ILUTERUS). Subtracting ILFULL from ILEMPTY yields ILUTERUS = 5.8 +/- 6.8 dB. Therefore, knowing the respective path lengths and normalizing for frequency, the mean tissue attenuation coefficients (A) are estimated to be AABD WALL = 1.39 dB/cm-MHz and AUTERUS = 0.14 dB/cm-MHz. These attenuation data suggest that the abdominal wall is the principal source of ultrasonic energy loss.


Apparent contribution of respiratory gas exchange to the in vitro "cell density effect" in ultrasonic cell lysis.

Ultrasonic damage to cells in vitro has been reported to vary dramatically with cell density; the particle density per se has been proposed to be responsible for this effect via interference with gas body activity. Reported here are the results of experiments designed to test the general postulate that the "cell density effect" can be explained in part by cellular modification of the suspension medium by respiratory gas exchange. Ultrasonic cell lysis is shown to occur at a much higher level in suspensions supplemented with the respiratory inhibitor NaCN than in control suspensions when suspension densities exceed 2 x 10(7) cells/mL. Moreover, at constant cell density, cell lysis diminishes with increasing pre-insonation incubation time at 37 degrees C. The rate of change in cell lysis with incubation time was diminished significantly by cyanide treatment. These observations are consistent with the postulate that respiratory O2:CO2 exchange enriches the medium in CO2 while depleting the medium of oxygen, which cavitates more readily than CO2, thereby diminishing the potential for cavitation-related cellular damage. However, this is only a partial explanation of the cell concentration dependence of cell lysis; cell density per se is an important factor in the "cell density effect."


Ultrasound-enhanced effects of adriamycin against murine tumors.

Earlier studies from our and other laboratories have demonstrated that ultrasound (US) enhances the cytotoxicity in vitro of the antitumor agent Adriamycin (Adr) (Harrison et al. 1991; Loverock et al. 1990; Saad and Hahn 1987, 1989; Yang et al. 1991; Yumita et al. 1987, 1989). We have now tested the possibility that this additional cytotoxicity can be translated into antitumor activity in vivo. Mice, bearing either a fibrosarcoma (RIF-1) or a melanoma (B-16) on their thighs, were injected with a single dose of Adr (10-20 mg/kg). The tumors were then heated locally to 41 degrees -43 degrees C for 30 min, either by insonation with US or by immersion of the animals' limbs into hot water baths. Antitumor efficacy was scored two ways: by serial measurements of tumor volume to determine the time for the tumor to double in size, or by determining the X-ray dose required to sterilize 50% of the tumors (TCD50) after the Adr-hyperthermia treatment. Both assays gave similar results. Ultrasound-induced hyperthermia was substantially more effective in enhancing Adr activity than was hyperthermia induced by the water bath. The mean-doubling time was 13 days for tumors treated with the combination of Adr and US and 6 days for tumors heated with a water bath immediately after injection of Adr. The TCD50 was 21.2 +/- 0.8 Gy for the combination of US and Adr and 36.1 +/- 0.9 Gy for the water bath heating and Adr.(ABSTRACT TRUNCATED AT 250 WORDS)


The sensitivity of Drosophila larvae to continuous-wave ultrasound.

The threshold for killing of freshly hatched Drosophila larvae exposed to continuous-wave (CW) ultrasound shows a minimum at approximately 0.3 MHz. This suggests that the stiffness of the material surrounding the gas bodies in the organism is comparable to water. From this, it is apparent that the gas bodies in three-day-old larvae that we have used in earlier studies are far larger than resonance size at the frequencies (1-5 MHz) used. Yet, these larvae were killed by short exposures to low-temporal-average-intensity pulsed ultrasound with peak intensities of the order of 10 W/cm2. Hence, it appears that "large" bubbles cannot be ignored in considerations of the biological effects of pulsed ultrasound and lithotripsy.


[Reparative processes of experimental Aitken III lesion. An animal experiment study].

This present study describes the fine structural aspects of experimentally induced defects of the proximal growth plate of the tibia in rabbits as simulation of epi-/methaphyseal fractures. We evaluated two different defect sizes. As important result we find in narrow defects of 0.5 mm no osseous bridging of the epiphyseal plate whereas with 2 mm defects there is partial transphyseal closure. Growth plate cartilage is thus capable of repairing spontaneously smaller defects.


[Ablation of hard biological tissue with the excimer laser].

Cutting and drilling of bone- and meniscus tissue were performed using a XeCl-excimer laser combined with a tapered fiber. Ablation speed on meniscus tissue is already sufficient, the thermal damage of the adjacent tissue is minimal. Increasing of energy transmission through special fibers promises higher ablation rates also on hard biological tissue and that promoted the interest in lasers again for accident surgeons.


[Effect of form elasticity of the prosthesis shaft in response to stress of the proximal femur].

Uncemented hip prostheses are characterized by a variable design of the stem. In these investigations, nine different prostheses were studied according to the model of a standard bone (Kunststoffnormfemur). After preparation of the cavity of the prostheses with original instruments and after its implantation, strain gauges were placed at 16 certain points. Measurements were carried out in steps of 200 N until reaching the maximal force of 2kN. Prostheses that are characterized by an anatomical design of the stem resemble the physiological nature of normal bone, in contrast to the models with a rectangular cross-section or with a stretched lateral shape of the stem.


[Thoracopulmonary complications of fresh fractures of the thoracic spine with neurologic damage].

The number of thoracic injuries associated to traumatic fractures of the spine is increasing. The multiple trauma rate in this retrospective study of 253 spinal injuries with neurological damage, which needed admission to the Intensive Care Unit, was of 55%. Blunt chest trauma was found in 86% of the multiple trauma group, especially in combination with fractures of the upper and middle thoracic spine (up to 100%), while head injuries appeared in only 58%. Hemopneumothorax was diagnosed in 88%, pulmonary contusion in 48% of the cases, leading to a high rate of recidivating atelectasis and pneumonia. Emergent chest computed tomography should therefore be obligatory in thoracic spine fractures.


[Possibilities for avoiding homologous blood transfusion in surgical interventions].

Alternative techniques to reduce the need for homologous blood transfusions are clinically available for several years. Actually a decision of our federal constitutional court (Bundesgerichtshof) outlined the medicolegal importance of autologous blood transfusion concepts. Pre-operative donation of red cells and/or plasma, acute normovolemic hemodilution, and intraoperative blood salvage and retransfusion will be discussed in terms of effectiveness, advantages, indications, and contraindications. In an emergency hemorrhage situation only the intraoperative blood salvage and retransfusion is available. The other autologous concepts are important in elective surgery.


[Experiences with the isoelastic prosthesis in treatment of humerus metastases].

39 patients with pathological fractures of the humerus were treated by isoelastic polyacetal endoprosthesis. Ten patients received a humeral-head-prosthesis and 32 a prosthesis of the humeral-shaft. The average survival time was nine months. Three times within the first group of twelve patients fracture of the cone of the prosthesis occurred. Therefore an additional stabilization of the contact zone between bone and prosthesis by plate-osteosynthesis was performed in the following 20 operations, preventing breakage of the material. In contrast to the conventional posterior approach to the humeral-shaft we chose a ventrolateral approach between the biceps and triceps muscle. This technique is less traumatic and leads to a shorter operation time. In patients with pathological humeral fractures a conception of treatment is demonstrated which provides an immediate stability by using endoprostheses to preserve the quality of life of oncological patients.


[Combined injury of the anterior cruciate ligament and the medial collateral ligament of the knee joint--results of two to six years follow-up of surgical treatment].

A retrospective study of 148 combined acute knee injuries with anterior cruciate and medial collateral ligament injuries was performed. Follow-up included 115 patients, 95 of whom were personally examined two to six years postoperatively. Proximal anterior cruciate ligament ruptures were treated with reinsertion in 96 patients, in case of intraligamentous lesions (44 times), augmentation with the semitendinosus tendon was performed. Medial collateral ligament lesions were explored during the operation. Reconstruction of intraligamentous ruptures was performed with sutures (120 times). Distal lesions were refixed with Burri plate or staple. A modified Ellison procedure was routinely performed. Postoperative treatment was cast-free and included immediate physiotherapy using a functional brace. Between the two groups with anterior cruciate ligament reinsertion and augmentation, no significant differences were observed in subjective evaluation (Lysholm score 85 vs. 88), activity level (Tegner score 5.5 vs. 5.4) or anterior stability (KT 1000 at 89 N 6.6 vs. 6.1 mm displacement). A clear pivot shift sign was noted in two knees with reinsertion and in none of the augmented group. Medial stability was reestablished almost completely, independent of the site of lesion or the reconstruction technique (average valgus movement at 30 degrees flexion 0.7+ vs. 0.5+ on injured/contralateral side). We conclude that reinsertion of femoral anterior cruciate ligament ruptures will reestablish anterior stability in most cases, although semitendinosus augmentation appears to give slightly more reliable results. Medial stability is gained by the site-depending reconstruction techniques. Whether intraligamentous medial collateral ligament lesions can be left alone with only the anterior cruciate ligament being reconstructed, cannot be answered by this study.


[Immobilization and early mobilization of malleolar fractures after osteosynthesis with resorbable bone screws].

71 patients with displaced ankle fracture were treated by using absorbable screws in the fixation of fractures. The follow-up time was 17 (13 to 33) months in average. The fixation devices were SR-PLLA (self-reinforced poly-L-lactide) and SR-PGA (self-reinforced polyglycolide) screws. 38 of the ankle fractures were immobilized with plaster cast and 33 ankle joints were mobilized immediately with a brace. An exact radiological result was achieved in 66 cases, insignificant displacement was observed in four cases and the result was poor in one patient. The result was classified as excellent in 62 patients, as good in eight patients and as poor in one patient. The patients treated postoperatively without plaster healed in a somewhat shorter time, but at one year check-up the differences in the clinical results were almost eliminated. Selected ankle fractures fixed with absorbable screws can be treated postoperatively with early mobilization without plaster.


[Traumatic hematoma of the adrenal gland simulating pheochromocytoma. A case report].

A young man with Weber B fracture had adrenalectomy under the suspicion of pheochromocytoma on the right side. Surprisingly hematoma of the right adrenal gland was found. This case is presented to point out the mechanism of trauma and diagnostic possibilities of the injury.


Microwave coagulation therapy on VX-2 carcinoma implanted in rabbit urinary bladders.

In order to evaluate the effectiveness of microwave coagulation therapy on urinary bladder carcinoma, we conducted a series of experiments using carcinoma VX-2 cells designed for the application on animal hosts. Three days after implantation of VX-2 cells into the bladder of the rabbits, microwave coagulation therapy was performed. The antitumor effect, i.e. the survival rate, the histological study and the immunological response of the microwave therapy was examined in comparison with the control group (no treatment), the partially cystectomized group and the sham-operated group (no tumor cell implantation). The results were obtained as follows. (1) The survival rate in the microwave group was greater than that in the control group. (2) The stimulation index value (SI), which represents humoral immunity, decreased postoperatively in all groups. In the microwave group, SI increased gradually beginning 21 days after the transient decrease. (3) Histological findings revealed severe degeneration, necrosis and complete eradication of the cancer cells of the bladder wall in the microwave group, however, perforation of the urinary bladder could not be detected. The results indicate that microwave coagulation therapy is an effective procedure for urinary bladder tumors. Furthermore, microwave therapy may also accelerate the inactivation of immunological suppressors in the carcinoma host, an additional benefit of the microwave procedure.


Evaluation of seminal vesicle characteristics by ultrasonography before and after ejaculation.

Twenty males underwent transrectal ultrasonography before and after ejaculation to examine possible alterations that could influence interpretation of seminal vesicle ultrasonography. The preejaculation length of 35 mm was significantly (p < 0.05) decreased to 30 mm after ejaculation. The mean width of the seminal vesicles was 13 mm before and 11 mm after ejaculation. The seminal vesicle volume was significantly diminished after ejaculation (p < 0.05). It therefore seems important to maintain a period of abstinence when evaluating the seminal vesicles by ultrasonography.


Lithiasis in the ileal conduit and the continent urinary pouch: two cases and a review.

We present 2 patients who developed stones (6 and 57 g) in the ileal conduit; the first stone was passed and the second required surgical removal; its nidus was a surgical staple. After a review of the literature which includes 25 other cases of stones in ileal conduits, as well as over 20 cases of stones in continent urinary pouches, it is concluded that the use of metallic staples in the construction of the ileal conduit or the continent urinary pouch should be abandoned.


The forgotten double J stent. Case report of a multifractured ureter stent.

An 81-year-old male patient was admitted to hospital because of macrohematuria. The clinical examination revealed a multifractured double J stent which had been placed 17 months before in another clinic because of hydronephrosis. In the reported case, a combined endoscopic and open surgical management was necessary to remove all fragments from the renal pelvis, the ureter and the bladder. Occlusion, encrustration and migration are among the most frequent risks of ureter stenting. The breakage of the stent, however, is a rare but severe complication. Therefore, patients should generally be controlled by sonography every 2 months and when malfunction of the stent is suspected, a cystogram should follow. In general, a stent exchange should be performed after 12 months.


[Percutaneous transluminal angioplasty of peripheral arteries: past, present and future].

Balloon percutaneous transluminal angioplasty (PTA) has been described in 1974 and has since been considerably refined with the improvement of balloon catheters, guide wires and radiology equipment. Laser and other mechanical recanalization devices have not hold to their initial promises. Clinical and angiographic indications for PTA have been better defined over the years, resulting in excellent clinical successes with low morbidity and very low mortality. PTA has become an almost painless procedure and may be done on an outpatient basis. It is considered as the treatment of first choice in suitable patients.


Delayed dehiscence of repaired bladder rupture.

A case of dehiscence of a previously repaired bladder rupture occurring 3 years after the original repair is reported. There was no obvious predisposing cause to this event. As this occurrence is very rare, it brings into question the need for long-term review of patients with conservatively treated bladder rupture.


Penile horn.

A case of cutaneous horn of the penis is reported, which was treated by electrosurgical excision. The possible etiopathogenesis with a review of the literature is discussed herein.


Diagnostic and predictive value of an immune monitoring program for complications after kidney transplantation.

We have tested an immune monitoring program consisting of cytofluorometric analysis of lymphocytic and monocytic markers, using a set of different monoclonal antibodies (mAb), in about 500 transplant patients including about 300 long-term renal allograft recipients. The high sensitivity (95%) of these cytofluorometric analyses in the peripheral blood allows to discriminate between acute rejection and other causes of deteriorated kidney transplant function (infection, toxicity, arteriopathy), especially in the late phase (> 1 year) after transplantation. Additionally, the immune monitoring is sufficient to predict success of antirejection therapy as early as a few days after onset of treatment. A life-threatening complication in allograft recipients is septic disease. Proceeding from immune parameters, septic patients were found to fall into two categories: those with decreased expression of HLA-DR on monocytes (< 20%, termed as 'immunoparalysis') and patients with nearly normal HLA-DR+ monocytes. Septic immunoparalysis requires drastic reduction of immunosuppression (mortality after drastic reduction: 8%; after marginal reduction or without reduction: 90%). We have not observed severe rejection as a consequence of reduced immunosuppression in such patients. Our immune monitoring seems to be useful for management of immunosuppression in patients with unclear deterioration in graft function as well as patients with septic complications in order to minimize two risks, i.e. death by sepsis or loss of graft.


Problems of the distal ureter in renal transplantation.

The incidence and mortality rates of urologic complications in renal transplantation have decreased significantly during the last decade. This was achieved by improved techniques of donor nephrectomy with preservation of the ureteric blood supply and refined procedures for the reconstruction of the urinary tract. Intra- and extravesical ureteroneocystostomies have shown to be the most reliable and preferred techniques to restore the urinary tract continuity. Beside ureteral ischemia and technical failure ureteral rejection is increasingly accepted as an important contributory factor for the development of ureteric fistula and stenosis formation. Controversy still exists concerning the pathogenesis of reflux into the graft and its impact on long-term graft function. Percutaneous and endoscopic procedures have supplemented and partially replaced open surgical management of ureteric fistulas and stenoses. By adherence to the principles described the frequency of urologic complications and its associated mortality rates can be minimized.


Secondary pyeloureterostomy after ureter necrosis in renal transplant recipients.

After kidney transplantation, urological complications account for significant morbidity necessitating reoperation in a substantial number of patients. In cases with urinary tract necrosis after renal transplantation secondary pyeloureterostomy represents an accepted method for urinary tract reconstruction. In our institution 2% of all kidney grafts required secondary pyeloureterostomy. In all cases the recipient's own ureter was investigated before reoperation by retrograde pyeloureterography. Pyeloureterostomy was performed with a standard technic, the recipients own kidney being removed in all but 5 patients. All 25 patients had normal kidney function immediately after secondary pyeloureterostomy. Urological complications occurred in 7 patients (anastomotic leakages in 4, stenosis in 3); 5 out of 7 complications were managed conservatively (nephrostomy, transureteral stenting). Two patients needed reexploration for reanastomosis. Our results confirm the simple and safe technic of pyeloureterostomy for urinary reconstruction in patients with ureter necrosis after renal transplantation.


Problems concerning the bladder in renal transplantation. Prognosis--replacement possibilities.

Problems arising from the lower urinary tract in patients with a terminal renal insufficiency are usually known long before transplantation; they can even be the cause of chronic renal failure. A careful investigation of morphology and function of upper and lower urinary tract before performing renal transplantation is still of great importance. In up to a quarter of the cases pathological findings can be recorded. Whether a supravesical urinary diversion or a bladder augmentation has to be performed in case of insufficient bladder function is dependent on the urodynamic results. However, so far there are no reliable prognostic factors indicating whether or not a bladder with increased capacity due to renal transplantation reacts with normal pressure. An investigation of the lower urinary tract also has to be carried out in patients who already have a supravesical urinary derivation at the time of renal transplantation, as a possible removal always has to be taken into consideration. Survival rate following transplantation in patients with a conduit is not lower than in those with a normal bladder.


Diagnosis and treatment of urological complications in kidney transplantation.

Between January 1973 and January 1990 we carried out 1,038 kidney transplantations using a transvesical end-to-side implantation of the ureter in the bladder without an antireflux mechanism. Moreover, 30 transplantations were done in 26 patients with a urinary diversion. We examined the urological complications in these 1,068 consecutive transplants. Urinary leakage and obstruction were the two main urological posttransplant complications. Severe leakage occurred in 21 patients (2.0%), and was treated by open surgery; 2 patients had a urinary diversion. The treatment of choice is a pyeloureterostomy (anastomosis between the transplant renal pelvis and the native ureter). There were 35 patients (3.3%) with severe ureteral obstruction of whom 5 had a urinary diversion. In 30 patients open surgical treatment of the obstruction was necessary and in 7 patients a percutaneous endourologic treatment was done (dilatation of a confined ureteral stricture in 6 patients and percutaneous stone treatment in 1). The postoperative mortality in the patients treated for leakage or obstruction was low: 4 patients (7%) died, 3 of septicemia due to leakage and 1 of pulmonary embolism after repair of the obstruction. The results of surgical treatment were good. The graft survival after 2 years in the group of urologically complicated transplants was 68% for the patients with leakage and 80% for those with obstruction. The 2-year graft survival in the patients without complications was 67% and 71% for the patients with a urinary diversion. We conclude from these results that urological complications after renal transplantation can be treated successfully by surgical (or percutaneous) correction.


Biochemistry of bladder cancer invasion and metastasis. Clinical implications.

In bladder cancer, the finding of infiltration signals the capability of a tumor to behave in an aggressive manner and potentially create a life-threatening situation. The ability to invade is carried in the tumor cell's complement of biochemical pathways as well as in its inability to preserve or restore rather than to disrupt normal tissue architecture. What determines the activation and deployment of these biochemical activities is unclear. That they occur, however, and can distinguish aggressive cancers likely to metastasize from cancers whose behavior is benign, is not. Recognizing and identifying these distinctions is an important step in designing new therapies to prevent a tumor's potential aggressive behavior, possibly reverse or at least contain any extensions that have occurred, and ultimately convert a potentially life-threatening situation to one with a more benign prognosis.


Molecular genetics and biochemical mechanisms in bladder cancer. Oncogenes, tumor suppressor genes, and growth factors.

Transitional-cell carcinoma of the bladder is believed to arise through a series of genetic changes affecting cell growth and proliferation. Two basic types of such genes have been described: protooncogenes and tumor suppressor genes. The former have not been studied extensively in bladder cancer, although there is evidence that c-erb B-2/neu is overexpressed. Loss of specific chromosomal regions, which is common in bladder tumors, may inactivate tumor suppressor genes, of which p53 has received the most attention. Work also has been done on epidermal growth factor and its receptor, yielding evidence that malignant and normal urothelium have different sensitivities to its action. Although several advances must be made before genetic changes come to the clinical forefront, the information now being gained with such speed holds considerable promise for diagnosis and treatment.


Basic epidemiologic and statistical methods in clinical research.

Various study designs and approaches to statistical analysis in clinical research have their own underlying rationales and limitations for interpretation. This information is presented in an intuitive and accessible manner, relying minimally on basic algebra. Epidemiologic concepts of study design and interpretation, bias and confounding, hypothesis testing, and sample size and power are explained. Statistical tests and their appropriate applications are discussed for mean comparisons (t tests and ANOVA), percentages (chi-square), survival analysis, and correlation and regression. Applicable nonparametric tests are also introduced.


Assessment of study design in clinical trials for bladder cancer.

Physicians and surgeons who treat bladder cancer must be able to judge the validity and relevance of clinical trials if they are to make appropriate recommendations to their patients. To do so, they must be familiar with the design of clinical trials and with the many problems that may confound their results and limit their validity. The present article has reviewed aspects of the design, analysis, and reporting of clinical trials with particular reference to bladder cancer. Nonrandomized studies are important in establishing the feasibility of new treatments and in providing preliminary information about effectiveness. However, selection of patients, together with many other types of bias, prevents a useful comparison of the results obtained in such trials with those obtained using alternative treatment strategies. Establishment of the value of a new type of treatment will usually require the conduct of a large randomized trial in which patients receive experimental or standard therapy by random assignment. While such trials may influence practice in an appropriate way, they must likewise be reviewed critically to ensure the validity of the results and generalizability to patients seen in a nontrial setting.


Staging of advanced bladder cancer. Current concepts and pitfalls.

Data presented in the preceding paragraphs should highlight to the reader several important features of clinical bladder cancer staging. Irrespective of the staging level being addressed, the available techniques uniformly have limitations, as well as advantages and disadvantages with respect to each other. A common shortcoming of both plain and cross-sectional techniques employing conventional X-rays is their lack of specificity. Every radiographic finding has an associated differential diagnosis in which neoplasia-related change is but one of many possibilities. Solitary abnormalities on bone scan or chest film serve as an excellent examples of this dilemma. The specificity of conventional imaging techniques is further compromised by attempts to increase sensitivity. As long as nonspecific anatomic changes are used as discriminating criteria, increases in test sensitivity will always occur at the price of specificity. It is hoped that advances in PET scanning and the use of isotope-labeled, tumor-selective monoclonal antibodies will overcome the limitations of currently available techniques. The significance of the limitations of a given test depends to some degree on whether the test is being used for clinical decision making or for patient stratification in a clinical trial. As an example, an aggressive transurethral resection of bladder tumors provides excellent information for clinical management but may introduce bias into multicenter studies in which this technique is not uniformly practiced. Similarly, the results of bimanual examination under anesthesia are important in the reference framework of the managing physician but are a poor quantifier of disease extent in multi-investigator clinical trials. Which staging studies are indicated and their optimal sequence for performance are influenced by pre-existing clinical information. Recognizing this, the staging algorithm in Figure 6 is intended to serve only as a guide to assist the clinician in the evaluation of patients with bladder neoplasms. As clarifications, several points concerning this algorithm merit mention. The literature suggests that as a single study, transurethral ultrasonography provides excellent local staging information. However, given that it is not widely available, the authors have chosen not to incorporate it into the staging schema. Optimally, it would be used immediately prior to transurethral resection of bladder tumors and bimanual examination. In addition, the algorithm lists MRI interchangeably with CT. While MRI appears to have slightly better sensitivity and specificity for both local and regional tumor stage relative to CT, its benefits are to some degree offset by its greater cost and the need to image the patient in multiple planes for lengthy intervals.(ABSTRACT TRUNCATED AT 400 WORDS)


Treatment of regionally advanced bladder cancer. An overview.

The finding of muscle-infiltrative bladder cancer is generally considered ominous, as 50% of patients who present with this condition are likely to develop distant metastases within 2 years. However, some types of infiltrative bladder cancer appear to have a less ominous prognosis. In order to assess the results of various therapies on regionally advanced bladder cancer, it is important to characterize the distinctions between the types with a poor prognosis (5-year survival rate 15% to 30%) and those with a better prognosis (5-year survival rate 50% to 85%). The former have a nodular architecture, infiltrate more deeply and in a tentacular pattern, and more often involve the bladder wall vasculature and lymphatics than does the latter type, which has papillary architecture and infiltrates on a broad front. These two types appear to respond differently to various treatments except systemic chemotherapy.


Transurethral resection in regionally advanced bladder cancer.

Various treatments have proved useful for disease control in some patients with regionally advanced bladder cancer. Transurethral resection may cure some patients with invasive disease, but identifying patients with such potential early in their course is difficult. A restaging transurethral resection helps indicate whether conservative management is feasible and, if not, which operation is appropriate. In some patients, transurethral resection may enhance the response to chemotherapy. Research is needed to identify those tumor characteristics associated with good results of conservative management of regionally advanced bladder cancer.


Partial cystectomy.

Partial cystectomy remains an uncommonly performed procedure in the urologist's armamentarium. Historically, it has had a limited role in the treatment of bladder cancer because of the variable reported success rate and because of the high success rate of local endoscopic excision. When patients with muscle-invasive lesions are appropriately selected, 5-year survival rates following partial cystectomy approximate those of radical cystectomy in the treatment of transitional-cell carcinoma while preserving a physiologically functioning bladder. Therefore, not only does partial cystectomy represent a valuable treatment option, but it appears to be the procedure of choice for local muscle-invasive transitional-cell carcinoma of the bladder when careful selection criteria are utilized. Future studies are needed to define its precise role in affording bladder preservation when used in association with adjuvant chemotherapy. Partial cystectomy also remains a surgical option for a variety of less common benign and malignant lesions of the bladder.


Radiation therapy in regionally advanced bladder cancer.

In conclusion, for patients undergoing bladder preservation, conventional external radiation therapy can no longer be recommended as a curative single modality. The usefulness of prognostic indicators, such as radiation responsiveness and tumor morphology, will have to be evaluated in light of newer treatment regimens. Patients should receive external radiation only if other therapies such as hyperfractionation, brachytherapy, intraoperative electrons, or combined chemotherapy and radiation therapy are unavailable or unable to be tolerated. Patients undergoing a planned cystectomy should receive preoperative radiation therapy until such time as neoadjuvant chemotherapy has been proved more or equally effective.


Systemic chemotherapy in regionally advanced bladder cancer. Theoretical considerations and results.

Integrating systemic chemotherapy into the treatment of patients with invasive bladder cancer, where the majority of deaths are from systemic relapse, is crucial if survival is to be improved. However, the global recommendation of a single treatment approach for all patients is becoming outdated as several groups have found that appropriately selected patients enjoy comparable survival whether treated by transurethral resection alone or by partial or radical cystectomy. Thus, refining case selection becomes a critical area of investigation. Patients with a high risk of systemic relapse should be considered for systemic therapy early in the course of the disease, ideally as part of a clinical trial. The availability of growth factors has reduced the toxicities of the regimens currently in use. Improvements in assessing biologic potential are required, so that treatment recommendations will allow patients the maximal chance of cure and maintenance of organ function, while minimizing toxicities in patients for whom systemic approaches are unwarranted. Of interest are recent reports that G-CSF may enhance tumor sensitivity to methotrexate in vitro and increase the sensitivity of implanted urothelial tumors to chemotherapy in nude mice. Such findings suggest an expanded role for these agents. Unfortunately, simple escalation of all components of a combination regimen does not appear to be a viable strategy, as it is unlikely to significantly increase CR proportions without prohibitive toxicities. However, as more is understood about drug resistance, and in particular its development in vivo, better sequencing of the available of options should be possible. The availability of effective salvage therapies suggests that this is an appropriate therapeutic approach. In addition, a number of strategies aimed at reversing the mdr phenotype are under study. These include calcium channel blockers such as verapamil, cyclosporin, and tamoxifen. Alternatively, some groups are investigating transfecting the mdr gene into bone marrow cells to reduce the sensitivity of these cells to cytotoxic agents. These novel designs can be tested both in patients with metastatic disease and in patients with locally advanced (T3b, T4, and N+) disease, who have a high risk of metastatic failure and low CR proportions to available regimens.


Combined treatment approaches in regionally advanced bladder cancer.

Multimodal therapy for locally advanced bladder carcinoma is being pursued in a wide diversity of protocols at this same time. While a number of innovative approaches are being explored, neoadjuvant and adjuvant chemotherapy in conjunction with cystectomy remains the dominant approach. The M-VAC regimen has become the dominant combination for the treatment of advanced bladder cancer; its use in an adjunctive setting is a logical progression. Although it is capable of effecting a response in the primary bladder lesion in a high percentage of cases, it is still not known whether survival will be enhanced. The use of radiosensitizing cytotoxics in conjunction with neoadjuvant chemotherapy, when combined with external-beam radiotherapy, is a provocative new approach that attempts to achieve both bladder salvage and enhanced patient survival. Completion of well-designed randomized studies will be necessary to determine whether these therapeutic innovations will yield any clinical benefit.


Treatment of chemotherapy-refractory metastatic urothelial tumors.

Patients with unresectable bladder carcinoma unresponsive to standard chemotherapy have a short survival, but recent clinical trials of salvage treatment have produced some good results. Changes in the dosage of M-VAC; 5-fluorouracil, alpha-interferon, and cisplatin; and gallium nitrate show promise.


Urinary diversion.

The patient facing cystectomy now has the opportunity to select various forms of urinary diversion. Although not all of the newer techniques have stood the test of time, preliminary results indicate that these continent diversions should be considered safe and effective. These procedures definitely alter the patient's lifestyle, resulting in a significantly better adjustment to the need for bladder removal. With experience, these procedures can be performed with morbidity rates very similar to those encountered with ileal conduit diversion. As with any procedures, however, appropriate patient selection and surgical training are imperative.


Management of advanced bladder cancer in the elderly.

Patients over the age of 70 years will become an increasingly important component of uro-oncologic practice. Although few published studies have specifically addressed this population, it is clear that the elderly can expect outcomes similar to younger patients in the management of advanced bladder cancer provided care is taken in planning. Of particular importance is an understanding of the pathophysiology of aging, of the possible implications of the causative factors for bladder cancer, and of the potential impact of advanced age on the biology of urothelial malignancy. Future studies should specifically address the problems of older patients with this malignancy to ensure the optimal possible outcome and definition of the most appropriate balance of toxicity and efficacy.


Renal pelvic cancer: a review of 611 patients treated in Illinois 1975-1985. Cancer Incidence and End Results Committee.

Renal pelvic transitional cell carcinoma constitutes about 7 percent of all kidney cancer. This report is a summary of 611 Illinois patients with this tumor treated between 1975 and 1985. Overall, the five-year relative survival rate was 62 percent and the observed five-year rate was 48 percent. Stage was a major determinant of survival, as expected, in these cancer patients. The Illinois experience is reviewed and compared with the accumulated literature experience with renal pelvic cancers since 1944.


Experience with schistosomiasis in renal transplantation.

Schistosomiasis involving the urinary tract has only occasionally been reported in North American literature and rarely from American hospital experience. Chronic infection may result in numerous abnormalities of the urinary tract which may interfere with the function of a transplanted kidney. Our institution has performed a number of renal transplants in patients who are from countries where schistosomiasis is endemic. Six patients in our group had evidence of schistosomal disease during their pretransplant evaluation and were appropriately treated. None of these patients had postoperative complications attributable to the schistosomal disease. We recommend that all patients who are from areas where urinary schistosomiasis is endemic undergo a cystoscopic examination and bladder biopsies in addition to the routine pretransplant urologic evaluation.


Objective treatment response to endocrine therapy in metastatic prostate cancer.

A ten-year review of 198 patients with Stage D2 prostate cancer identified 13 patients (6.6%) who exhibited objective responses to hormonal treatment, as indicated by regression of a positive bone scan, CT scan, or chest x-ray film. Four patients had complete responses and 9 patients achieved partial responses as judged by the National Prostatic Cancer Project criteria. Median survival for those with objective treatment response has not yet been reached (> 44 months) compared with twenty-four months for the nonresponders (p = 0.00006). Although relatively uncommon, objective treatment response in Stage D2 prostate cancer is correlated with an improved prognosis.


Anchor fixation and other modifications of endoscopic bladder neck suspension.

The long-term efficacy of surgical treatment of stress urinary incontinence can be improved by modifications that reduce the possibility of suspending suture detachment. Fifty-three women with stress urinary incontinence underwent consecutive endoscopic bladder neck suspensions with new modifications developed in an effort to decrease suspending suture detachment. Those modifications included: (1) technique of needle passage to capture a maximum volume of urethropelvic fascia lateral to the bladder neck and urethra while avoiding injury to the bladder, (2) pubic bone fixation of the suspending suture using a small anchor developed for orthopedic use, and (3) a simple technique to limit tension of the suspending sutures. Procedures were outpatient in 60 percent of patients (93% of the last 27 patients). Seventy percent of patients did not require intermittent catheterization beyond the day when their indwelling catheter was removed. The postoperative success rate (absence of stress urinary incontinence) at one month was 100 percent. There were 4 failures on follow-up up to fifteen months. Urgency incontinence decreased from 59 percent preoperatively to 15 percent postoperatively. The complication of osteitis pubis was not noted. Patient rating of satisfaction postoperatively was high. These modifications constitute a safe alternative to procedures that effectively suspend the bladder neck. An assessment of any change in long-term efficacy as a result of these modifications will require continued follow-up.


Penile calcification in maintenance hemodialysis patients.

Penile calcification was detected in 6 of 32 patients (19%) with end-stage renal disease (ESRD) using soft tissue x-ray techniques. Having been maintained on hemodialysis for a minimum of one year, all the affected patients showed clinical evidence of secondary hyperparathyroidism and calcification in the blood vessels of some other tissues. All had erectile impotence, while in 1 patient gangrene of the penis developed. Penile calcification is probably more common in ESRD patients than realized and should be looked for as a possible cause of impotence in male patients treated with maintenance hemodialysis.