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Biomedical subjects

A Russo

Publications and source records attributed to A Russo.

At least 595 records · Page 33Linked to original sources

[Experiences in experimental microneurosurgery].

The authors present their experiences in experimental micro-neuro-surgery referring to the last 2 years. In the field of vascular microsurgery, they explored: the possibility of performing end-to-side anastomoses reducing to few minutes the blood flow interruption in the receiving vessel; experimental reconstructive techniques of the arterial wall in case of giant aneurysm; micro-anastomoses between vessels with calibre smaller than 1 mm. The possibility of carrying out nervous anastomoses between intercostal and lumbar nerves to re-innervate these latter has been also examined on the basis of experimental trials.

Animals↗

Glutathione depletion greatly reduces neocarzinostatin cytotoxicity in Chinese hamster V79 cells.

The role of the intracellular thiol glutathione in the reductive activation of neocarzinostatin was investigated in Chinese hamster V79 cells. The cells were pretreated with agents that either lower (buthionine sulfoximine or diethyl maleate) or elevate (oxothiazolidine carboxylate) intracellular glutathione levels. These cells were then exposed to 1-5 micrograms/ml neocarzinostatin for 1 h and assayed for survival. Depletion of glutathione to levels at or below the limit of detection resulted in a marked reduction in neocarzinostatin cytotoxicity, while increasing glutathione levels to 250% of control values had little or no effect on neocarzinostatin toxicity. High performance liquid chromatography analysis of cysteine in untreated and glutathione-depleted cells showed cysteine levels lower than 0.2 microM, indicating that cysteine does not play a major role in the reductive activation of neocarzinostatin in untreated or glutathione-depleted cells. When intracellular cysteine levels were artificially elevated by oxothiazolidine carboxylate treatment of glutathione-depleted cells, neocarzinostatin toxicity was about two-thirds that seen in cells with normal glutathione levels. In cell-free systems, others have shown that reducing agents such as 2-mercaptoethanol are necessary for the activation of neocarzinostatin to a species that will cleave DNA. In this study, we have identified glutathione as the major cellular reducing agent for the activation of neocarzinostatin in a mammalian cell line.

Animals↗

Adaptive cellular response to hyperthermia: 31P-NMR studies.

Dynamic intracellular ATP and Pi levels were measured non-invasively for Chinese hamster V79 cells by 31P-NMR under conditions of thermotolerance and heat-shock protein induction. High densities of cells were embedded in agarose strands, placed within a standard NMR sample tube, and perfused with medium maintained either at 37 or 43 degrees C at pH 7.35. Cell survival and heat-shock protein synthesis were assessed either from parallel monolayer cultures or cells dislodged from the agarose strands post-treatment. Thermotolerance (heat resistance) and heat-shock protein synthesis was induced by a 1 h exposure to 43 degrees C followed by incubation for 5 h at 37 degrees C. After the 5 h incubation at 37 degrees C, marked thermal resistance was observed in regard to survival with concomitant synthesis of two major heat-shock proteins at 70 and 103 kDa. Studies were also conducted where tolerance and heat-shock protein synthesis were partially inhibited by depletion of cellular glutathione (GSH) prior to and during heat treatment. Dynamic measurement of intracellular ATP of cells heated with or without GSH depletion revealed no change in steady-state levels immediately after heating or during the 5 h post-heating incubation at 37 degrees C where thermotolerance and heat-shock proteins develop. These data are consistent with other reported data for mammalian cells and indicate that the steady-state ATP levels in mammalian cells remain unchanged during and after the acquisition of the thermotolerant state.

Adenosine Triphosphate↗

Abnormal visual-evoked potentials in leukemic children after cranial radiation.

Visual-evoked potentials (VEPs) were studied in 55 asymptomatic children with leukemia or solid tumors in remission in order to detect subclinical demyelination of the optic pathway after CNS prophylaxis. In group I (11 patients with ALL studied prospectively), VEP latency was increased in ten after cranial radiation (CR) as compared with previous values. Group II (18 patients with ALL in maintenance) and group III (16 patients with ALL off therapy) were studied retrospectively and VEP latency was found above normal limits in 33 and 31%, respectively. In group IV (four patients with solid tumors and six with leukemia, all of whom received no CR), VEP latency was normal despite periodical intrathecal methotrexate administrations to five of them. We conclude that CR determines a slowing of conduction on VEP test, probably due to demyelination of the optic pathway, in a high proportion of patients. The future clinical significance of these findings must be established throughout a prolonged follow-up period.

Brain↗

Estrogen and progesterone receptors in the human vagina.

Estrogen (E) and progesterone (Pg) receptor (R) levels were determined in the human vagina in relation to menopausal status, day of ovarian cycle and pregnancy. The results obtained confirmed that the human vagina contains ER and, in addition, demonstrated for the first time the presence of PgR in this organ in humans. In cycling women, ER and PgR did not vary significantly during the ovarian cycle; however low (less than or equal to 10 fmoles/mg cytosol protein) concentrations of PgR were more frequently (6 out of 8 cases) detected during the secretory phase. No substantial difference was seen in ER and PgR values between anterior and posterior wall of the vagina. In postmenopausal patients the levels of ER (range: 10-83 fmoles/mg) were similar to those found in premenopause (range: 12-78 fmoles/mg). As regards PgR, the majority (14 out of 20) of vaginae were devoid of PgR, 4 had a very low (less than or equal to 6 fmoles/mg) PgR content and only 2 cases had a PgR level higher than 10 fmol/mg cytosol protein. In pregnant patients (6th to 8th week) ER were found in all vaginae, while PgR were present only in some cases (3 out of 8). It was concluded that the behavior of ER in the human vagina seems different from that in the human endometrium, since ER levels do not vary in relation to changes in the concentrations of sexual hormones in the circulation. On the contrary, PgR levels appear to depend on blood estradiol and progesterone concentration, as in other target tissues.

Adult↗

A phase I study of intravenous iododeoxyuridine as a clinical radiosensitizer.

Twenty-four patients with locally advanced (19 patients) or metastatic (5 patients) tumors were treated in a Phase I study combining constant intravenous infusions of iododeoxyuridine (IUdR) and hyperfractionated radiation therapy. IUdR was given as a constant infusion for 12 hours/day for two separate 14-day infusion periods in most patients. The dose of IUdR was escalated from 250 to 1200 mg/m2/12-hour infusion in this study. The initial tumor volume was treated to 45 Gy/1.5 Gy BID/3 weeks followed by a cone-down boost to 20-25 Gy/1.25 Gy BID/2 weeks after a planned 2-week break. THe IUdR infusion preceded the initial and cone-down irradiation by 1 week. Local acute toxicity (within the radiation volume) was uncommon and few patients required an alteration of the planned treatment schedule. Two patients developed late local toxicity with one patient showing clinical signs of radiation hepatitis and another patient developing a large bowel obstruction that required surgical bypass. Dose-limiting systemic toxicity was confined to the bone marrow with moderate to severe thrombocytopenia developing on Day 10-14 of infusions at 1200 mg/m2/12 hours. Mild stomatitis and partial alopecia occurred in some patients at this dose level. No systemic skin toxicity was seen. Pharmacology studies revealed steady-state arterial plasma levels of IUdR of 1 to 8 X 10(-6) M over the dose range used. In vivo IUdR incorporation into tumors was studied in three patients with high-grade sarcomas using an anti-IUdR monoclonal antibody and immunohistochemistry and demonstrated incorporation in up to 50-70% of tumor cells. The preliminary treatment results, particularly in patients with unresectable sarcomas, are encouraging. In comparison to our previous experience with intravenous bromodeoxyuridine, this Phase I study of IUdR shows less systemic toxicity (especially to skin), higher (2-3X) steady-state arterial levels, and comparable in vivo tumor cell incorporation.

Biopsy↗

Profile of medical ICU vs. ward patients in an acute care hospital.

Demographic characteristics, severity of illness, resource utilization, and outcome were compared for 351 medical ICU (MICU) and 329 ward patients of a large, urban, tertiary care hospital. Patients were similar in age, race, sex, and insurance coverage. Both MICU and ward patients had similar health status distributions 3 to 6 months before hospitalization. Severity of illness, as measured by the Acute Physiology Score was significantly higher in the MICU patients, although there was considerable overlap in the distributions. Resource utilization, as measured by the Therapeutic Intervention Scoring System (TISS), was also significantly higher in the MICU; again, the distributions of the two groups overlapped, although mostly for low values of TISS. Of the MICU sample, 28% to 30% never required active therapeutic interventions; 11% of the ward sample received active treatment. The significant overlap between MICU and ward distributions of severity of illness and resource utilization has implications for admission and discharge policies.

Delivery of Health Care↗

Cranial irradiation and platelet monoamine oxidase in ALL.

Prophylactic cranial irradiation in acute lymphoblastic leukemia (ALL) has been held responsible for long-term neuropsychological sequelae. This study evaluates the activity of monoamine oxidase (MAO) in children with ALL in first complete remission both before and after cranial irradiation, given to prevent central nervous system involvement. There was a significant decrease (p less than 0.025) in platelet MAO activity shortly after cranial irradiation. MAO activity values were in the normal range in patients investigated 3 months or more after the radiation treatment was completed. The pathogenesis and clinical relevance of this decrease are discussed.

Adolescent↗

Increase of F cells during acute hemolysis in glucose-6-phosphate dehydrogenase-deficient males.

Five male Sicilian children with glucose-6-phosphate dehydrogenase deficiency were studied shortly after hemolytic crisis in order to evaluate the immediate effects of massive hemolysis on fetal Hb (HbF) levels and the number of circulating F cells. Hematological values seen 4 months after the children recovered from the crisis were considered representative of the patients' steady state. All patients had an increase in HbF levels (2.26 +/- 0.24%) and F cell number (29 +/- 4.79%) in the acute phase and their HbF values and F cells returned to normal range at control. Globin synthesis was balanced in the peripheral blood and bone marrow and there was a small peak of gamma chains. Globin chain electrophoresis showed that both G gamma and A gamma genes were active in all patients. These results confirm that hemolytic stress produces increased F cell release in peripheral blood. Such release is rapid enough (less than 72 h) to be consistent with the hypothesis of an induction of HbF synthesis in late erythroid precursors.

Acute Disease↗

Oxygen dependence of hematoporphyrin derivative-induced photoinactivation of Chinese hamster cells.

The oxygen dependence of hematoporphyrin derivative (HPD)-induced photoinactivation of Chinese hamster V79 cells was examined. Cells were treated with HPD (25 micrograms/ml) for 2 h and subsequently exposed to red light (greater than 590 nm) under either aerated or hypoxic (less than 10 ppm O2) conditions. Hypoxic cells were found to be extremely resistant to the lethal effects of HPD and light. The electron-affinic X-ray hypoxic cell sensitizer, SR-2508, did not sensitize hypoxic HPD-treated cells to light. The clinical implications of these findings are discussed, with consideration of the possibility that hypoxic areas in tumors may limit HPD phototherapy.

Animals↗

The influence of sorbitol on the glycogenolytic pathway.

The following report presents the results of a study conducted on the influence of sorbitol on levels of glycogen, phosphorylase a (E.C. 2.4.1.1.) and phosphorylase kinase (E.C.2.7.1.38) in slices of rat liver. In addition, it presents data concerning the effects of sorbitol on the activities of phosphorylase a and phosphorylase kinase purified from rabbit muscle. The data reveal a limitation in the glycogenolytic process which seems, in part, due to the inactivation of the phosphorylase a and phosphorylase kinase. Gel-filtration techniques showed, in fact, a breakdown of these two oligomeric enzymes into inactive subunits following incubation with sorbitol.

Animals↗

In vivo incorporation of bromodeoxyuridine into proliferating cells in the marrow and its effects on granulocyte-macrophage progenitor cells.

Bromodeoxyuridine (BUdR), a potential radiosensitizing drug, was given by intravenous infusion at 650-1000 mg/m2/day for up to 12 days. In vivo incorporation into human bone marrow was assayed by differential chromatid staining as well as by comparison of in vitro radiation survival curves of granulocyte-macrophage progenitor cells scored at both day 7 and day 14. Although a difference was found in the radiation survival of control (untreated) day-7 progenitor cells (Do = 1.39 Gy) and day-14 progenitor cells (Do = 0.89 Gy), a similar degree of in vitro radiosensitization was found for BUdR-treated bone marrow progenitor cells scored at day 7 and day 14. The culture technique provided a bioassay for the in vivo action of BUdR. BUdR treatment produced transient moderate myelosuppression that probably resulted from BUdR incorporation into normal marrow cells.

Bone Marrow↗

Treatment of murine intraperitoneal ovarian ascitic tumor with hematoporphyrin derivative and laser light.

An ascitic murine tumor, ovarian embryonal carcinoma, was used as a model of human ovarian carcinoma restricted to the peritoneum. The tumor was treated with a combination of hematoporphyrin derivative (HPD) and i.p. 514-nm laser light. Mice were given injections of 2 X 10(5) tumor cells, and by 9 days, there were 2 to 4 g of ascitic tumor/mouse. On Day 9, mice (68) were treated as follows: (12) no treatment; (12) only HPD (50 mg/kg i.p.); (12) laser only (9.6 J for 16 min); and (32) HPD (50 mg/kg i.p.) and 2 h later, laser treatment. On Day 15, a second treatment with HPD and laser was given to 15 mice. All mice not receiving HPD-laser treatment died between Days 20 and 23. The response rate as determined by decrease in weight and abdominal size for HPD-laser-treated mice was 90%, but the response was short, and all but one animal died by Day 34. However, 6 of 15 of the twice-treated group are alive at 90 days and considered cured. Photoradiotherapy with HPD for i.p. ascitic tumors appears to have promise as a treatment modality.

Animals↗